The Stroke-Induced Blood-Brain Barrier Disruption: Current Progress of Inspection Technique, Mechanism, and Therapeutic Target

Takeshi       Okada; Hidenori       Suzuki; Zachary    D.    Travis; John    H.    Zhang
doi:10.2174/1570159X18666200528143301
Abstract

Stroke is one of the leading causes of mortality and morbidity worldwide. The bloodbrain barrier (BBB) is a characteristic structure of microvessel within the brain. Under normal physiological conditions, the BBB plays a role in the prevention of harmful substances entering into the brain parenchyma within the central nervous system. However, stroke stimuli induce the breakdown of BBB leading to the influx of cytotoxic substances, vasogenic brain edema, and hemorrhagic transformation. Therefore, BBB disruption is a major complication, which needs to be addressed in order to improve clinical outcomes in stroke. In this review, we first discuss the structure and function of the BBB. Next, we discuss the progress of the techniques utilized to study BBB breakdown in in-vitro and in-vivo studies, along with biomarkers and imaging techniques in clinical settings. Lastly, we highlight the mechanisms of stroke-induced neuroinflammation and apoptotic process of endothelial cells causing BBB breakdown, and the potential therapeutic targets to protect BBB integrity after stroke. Secondary products arising from stroke-induced tissue damage provide transformation of myeloid cells such as microglia and macrophages to pro-inflammatory phenotype followed by further BBB disruption via neuroinflammation and apoptosis of endothelial cells. In contrast, these myeloid cells are also polarized to anti-inflammatory phenotype, repairing compromised BBB. Therefore, therapeutic strategies to induce anti-inflammatory phenotypes of the myeloid cells may protect BBB in order to improve clinical outcomes of stroke patients.
Keywords: Blood-brain barrier, macrophage, microglia, neuroinflammation, programmed cell death, stroke, tight junction.
« Previous Next »
Graphical Abstract

[1] 
Feigin, V.L.; Norrving, B.; Mensah, G.A. Global Burden of Stroke. Circ. Res.,  2017, 120(3), 439-448.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.308413] [PMID: 28154096] 
[2] 
Benjamin, E.J.; Blaha, M.J.; Chiuve, S.E.; Cushman, M.; Das, S.R.; Deo, R.; de Ferranti, S.D.; Floyd, J.; Fornage, M.; Gillespie, C.; Isasi, C.R.; Jiménez, M.C.; Jordan, L.C.; Judd, S.E.; Lackland, D.; Lichtman, J.H.; Lisabeth, L.; Liu, S.; Longenecker, C.T.; Mackey, R.H.; Matsushita, K.; Mozaffarian, D.; Mussolino, M.E.; Nasir, K.; Neumar, R.W.; Palaniappan, L.; Pandey, D.K.; Thiagarajan, R.R.; Reeves, M.J.; Ritchey, M.; Rodriguez, C.J.; Roth, G.A.; Rosamond, W.D.; Sasson, C.; Towfighi, A.; Tsao, C.W.; Turner, M.B.; Virani, S.S.; Voeks, J.H.; Willey, J.Z.; Wilkins, J.T.; Wu, J.H.; Alger, H.M.; Wong, S.S.; Muntner, P. American Heart Association Statistics Committee and Stroke Statistics Subcommittee Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation,  2017, 135(10), e146-e603.
[http://dx.doi.org/10.1161/CIR.0000000000000485] [PMID: 28122885] 
[3] 
Prabhakarpandian, B.; Shen, M-C.; Nichols, J.B.; Mills, I.R.; Sidoryk-Wegrzynowicz, M.; Aschner, M.; Pant, K. SyM-BBB: a microfluidic Blood Brain Barrier model. Lab Chip,  2013, 13(6), 1093-1101.
[http://dx.doi.org/10.1039/c2lc41208j] [PMID: 23344641] 
[4] 
Abdullahi, W.; Tripathi, D.; Ronaldson, P.T. Blood-brain barrier dysfunction in ischemic stroke: targeting tight junctions and transporters for vascular protection. Am. J. Physiol. Cell Physiol.,  2018, 315(3), C343-C356.
[http://dx.doi.org/10.1152/ajpcell.00095.2018] [PMID: 29949404] 
[5] 
Alluri, H.; Wiggins-Dohlvik, K.; Davis, M.L.; Huang, J.H.; Tharakan, B. Blood-brain barrier dysfunction following traumatic brain injury. Metab. Brain Dis.,  2015, 30(5), 1093-1104.
[http://dx.doi.org/10.1007/s11011-015-9651-7] [PMID: 25624154] 
[6] 
Mracsko, E.; Veltkamp, R. Neuroinflammation after intracerebral hemorrhage. Front. Cell. Neurosci.,  2014, 8, 388.
[http://dx.doi.org/10.3389/fncel.2014.00388] [PMID: 25477782] 
[7] 
Turner, R.J.; Sharp, F.R. Implications of MMP9 for Blood Brain Barrier Disruption and Hemorrhagic Transformation Following Ischemic Stroke. Front. Cell. Neurosci.,  2016, 10, 56.
[http://dx.doi.org/10.3389/fncel.2016.00056] [PMID: 26973468] 
[8] 
Klatzo, I. Pathophysiological aspects of brain edema. Acta Neuropathol.,  1987, 72(3), 236-239.
[http://dx.doi.org/10.1007/BF00691095] [PMID: 3564903] 
[9] 
Balami, J.S.; Chen, R-L.; Grunwald, I.Q.; Buchan, A.M. Neurological complications of acute ischaemic stroke. Lancet Neurol.,  2011, 10(4), 357-371.
[http://dx.doi.org/10.1016/S1474-4422(10)70313-6] [PMID: 21247806] 
[10] 
Claassen, J.; Carhuapoma, J.R.; Kreiter, K.T.; Du, E.Y.; Connolly, E.S.; Mayer, S.A. Global cerebral edema after subarachnoid hemorrhage: frequency, predictors, and impact on outcome. Stroke,  2002, 33(5), 1225-1232.
[http://dx.doi.org/10.1161/01.STR.0000015624.29071.1F] [PMID: 11988595] 
[11] 
Russin, J.J.; Montagne, A.; D’Amore, F.; He, S.; Shiroishi, M.S.; Rennert, R.C.; Depetris, J.; Zlokovic, B.V.; Mack, W.J. Permeability imaging as a predictor of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. J. Cereb. Blood Flow Metab.,  2018, 38(6), 973-979.
[http://dx.doi.org/10.1177/0271678X18768670] [PMID: 29611451] 
[12] 
Latour, L.L.; Kang, D-W.; Ezzeddine, M.A.; Chalela, J.A.; Warach, S. Early blood-brain barrier disruption in human focal brain ischemia. Ann. Neurol.,  2004, 56(4), 468-477.
[http://dx.doi.org/10.1002/ana.20199] [PMID: 15389899] 
[13] 
Hjort, N.; Wu, O.; Ashkanian, M.; Sølling, C.; Mouridsen, K.; Christensen, S.; Gyldensted, C.; Andersen, G.; Østergaard, L. MRI detection of early blood-brain barrier disruption: parenchymal enhancement predicts focal hemorrhagic transformation after thrombolysis. Stroke,  2008, 39(3), 1025-1028.
[http://dx.doi.org/10.1161/STROKEAHA.107.497719] [PMID: 18258832] 
[14] 
Edgell, R.C.; Vora, N.A. Neuroimaging markers of hemorrhagic risk with stroke reperfusion therapy. Neurology,  2012, 79(13)(Suppl. 1), S100-S104.
[http://dx.doi.org/10.1212/WNL.0b013e3182695848] [PMID: 23008382] 
[15] 
Khatri, R.; McKinney, A.M.; Swenson, B.; Janardhan, V. Blood-brain barrier, reperfusion injury, and hemorrhagic transformation in acute ischemic stroke. Neurology,  2012, 79(13)(Suppl. 1), S52-S57.
[http://dx.doi.org/10.1212/WNL.0b013e3182697e70] [PMID: 23008413] 
[16] 
Shobha, N.; Buchan, A.M.; Hill, M.D. Canadian Alteplase for Stroke Effectiveness Study (CASES). Thrombolysis at 3-4.5 hours after acute ischemic stroke onset--evidence from the Canadian Alteplase for Stroke Effectiveness Study (CASES) registry. Cerebrovasc. Dis.,  2011, 31(3), 223-228.
[http://dx.doi.org/10.1159/000321893] [PMID: 21178345] 
[17] 
Hacke, W.; Furlan, A.J.; Al-Rawi, Y.; Davalos, A.; Fiebach, J.B.; Gruber, F.; Kaste, M.; Lipka, L.J.; Pedraza, S.; Ringleb, P.A.; Rowley, H.A.; Schneider, D.; Schwamm, L.H.; Leal, J.S.; Söhngen, M.; Teal, P.A.; Wilhelm-Ogunbiyi, K.; Wintermark, M.; Warach, S. Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI perfusion-diffusion weighted imaging or perfusion CT (DIAS-2): a prospective, randomised, double-blind, placebo-controlled study. Lancet Neurol.,  2009, 8(2), 141-150.
[http://dx.doi.org/10.1016/S1474-4422(08)70267-9] [PMID: 19097942] 
[18] 
Smith, W.S.; Sung, G.; Starkman, S.; Saver, J.L.; Kidwell, C.S.; Gobin, Y.P.; Lutsep, H.L.; Nesbit, G.M.; Grobelny, T.; Rymer, M.M.; Silverman, I.E.; Higashida, R.T.; Budzik, R.F.; Marks, M.P. MERCI Trial Investigators Safety and efficacy of mechanical embolectomy in acute ischemic stroke: results of the MERCI trial. Stroke,  2005, 36(7), 1432-1438.
[http://dx.doi.org/10.1161/01.STR.0000171066.25248.1d] [PMID: 15961709] 
[19] 
Smith, W.S.; Sung, G.; Saver, J.; Budzik, R.; Duckwiler, G.; Liebeskind, D.S.; Lutsep, H.L.; Rymer, M.M.; Higashida, R.T.; Starkman, S.; Gobin, Y.P.; Frei, D.; Grobelny, T.; Hellinger, F.; Huddle, D.; Kidwell, C.; Koroshetz, W.; Marks, M.; Nesbit, G.; Silverman, I.E. Multi MERCI Investigators Mechanical thrombectomy for acute ischemic stroke: final results of the Multi MERCI trial. Stroke,  2008, 39(4), 1205-1212.
[http://dx.doi.org/10.1161/STROKEAHA.107.497115] [PMID: 18309168] 
[20] 
Chen, H.; Zhu, G.; Liu, N.; Li, Y.; Xia, Y. Applications and development of permeability imaging in ischemic stroke. Exp. Ther. Med.,  2018, 16(3), 2203-2207.
[http://dx.doi.org/10.3892/etm.2018.6454] [PMID: 30186459] 
[21] 
Lucke-Wold, B.P.; Logsdon, A.F.; Manoranjan, B.; Turner, R.C.; McConnell, E.; Vates, G.E.; Huber, J.D.; Rosen, C.L.; Simard, J.M. Aneurysmal subarachnoid hemorrhage and neuroinflammation: A comprehensive review. Int. J. Mol. Sci.,  2016, 17(4), 497.
[http://dx.doi.org/10.3390/ijms17040497] [PMID: 27049383] 
[22] 
Veksler, R.; Shelef, I.; Friedman, A. Blood-brain barrier imaging in human neuropathologies. Arch. Med. Res.,  2014, 45(8), 646-652.
[http://dx.doi.org/10.1016/j.arcmed.2014.11.016] [PMID: 25453223] 
[23] 
Chen, S.; Feng, H.; Sherchan, P.; Klebe, D.; Zhao, G.; Sun, X.; Zhang, J.; Tang, J.; Zhang, J.H. Controversies and evolving new mechanisms in subarachnoid hemorrhage. Prog. Neurobiol.,  2014, 115, 64-91.
[http://dx.doi.org/10.1016/j.pneurobio.2013.09.002] [PMID: 24076160] 
[24] 
Gattringer, T.; Valdes Hernandez, M.; Heye, A.; Armitage, P.A.; Makin, S.; Chappell, F.; Pinter, D.; Doubal, F.; Enzinger, C.; Fazekas, F.; Wardlaw, J.M. Predictors of Lesion Cavitation After Recent Small Subcortical Stroke. Transl. Stroke Res.,  2019, 11(3), 402-411.
[PMID: 31705427] 
[25] 
Pavlovsky, L.; Seiffert, E.; Heinemann, U.; Korn, A.; Golan, H.; Friedman, A. Persistent BBB disruption may underlie alpha interferon-induced seizures. J. Neurol.,  2005, 252(1), 42-46.
[http://dx.doi.org/10.1007/s00415-005-0596-3] [PMID: 15672209] 
[26] 
Tomkins, O.; Shelef, I.; Kaizerman, I.; Eliushin, A.; Afawi, Z.; Misk, A.; Gidon, M.; Cohen, A.; Zumsteg, D.; Friedman, A. Blood-brain barrier disruption in post-traumatic epilepsy. J. Neurol. Neurosurg. Psychiatry,  2008, 79(7), 774-777.
[http://dx.doi.org/10.1136/jnnp.2007.126425] [PMID: 17991703] 
[27] 
Seiffert, E.; Dreier, J.P.; Ivens, S.; Bechmann, I.; Tomkins, O.; Heinemann, U.; Friedman, A. Lasting blood-brain barrier disruption induces epileptic focus in the rat somatosensory cortex. J. Neurosci.,  2004, 24(36), 7829-7836.
[http://dx.doi.org/10.1523/JNEUROSCI.1751-04.2004] [PMID: 15356194] 
[28] 
Tomkins, O.; Friedman, O.; Ivens, S.; Reiffurth, C.; Major, S.; Dreier, J.P.; Heinemann, U.; Friedman, A. Blood-brain barrier disruption results in delayed functional and structural alterations in the rat neocortex. Neurobiol. Dis.,  2007, 25(2), 367-377.
[http://dx.doi.org/10.1016/j.nbd.2006.10.006] [PMID: 17188501] 
[29] 
Lapilover, E.G.; Lippmann, K.; Salar, S.; Maslarova, A.; Dreier, J.P.; Heinemann, U.; Friedman, A. Peri-infarct blood-brain barrier dysfunction facilitates induction of spreading depolarization associated with epileptiform discharges. Neurobiol. Dis.,  2012, 48(3), 495-506.
[http://dx.doi.org/10.1016/j.nbd.2012.06.024] [PMID: 22782081] 
[30] 
David, Y.; Cacheaux, L.P.; Ivens, S.; Lapilover, E.; Heinemann, U.; Kaufer, D.; Friedman, A. Astrocytic dysfunction in epileptogenesis: consequence of altered potassium and glutamate homeostasis? J. Neurosci.,  2009, 29(34), 10588-10599.
[http://dx.doi.org/10.1523/JNEUROSCI.2323-09.2009] [PMID: 19710312] 
[31] 
Friedman, A.; Kaufer, D.; Heinemann, U. Blood-brain barrier breakdown-inducing astrocytic transformation: novel targets for the prevention of epilepsy. Epilepsy Res.,  2009, 85(2-3), 142-149.
[http://dx.doi.org/10.1016/j.eplepsyres.2009.03.005] [PMID: 19362806] 
[32] 
Ivens, S.; Kaufer, D.; Flores, L.P.; Bechmann, I.; Zumsteg, D.; Tomkins, O.; Seiffert, E.; Heinemann, U.; Friedman, A. TGF-beta receptor-mediated albumin uptake into astrocytes is involved in neocortical epileptogenesis. Brain,  2007, 130(Pt 2), 535-547.
[http://dx.doi.org/10.1093/brain/awl317] [PMID: 17121744] 
[33] 
Tomkins, O.; Feintuch, A.; Benifla, M.; Cohen, A.; Friedman, A.; Shelef, I. Blood-brain barrier breakdown following traumatic brain injury: a possible role in posttraumatic epilepsy. Cardiovasc. Psychiatry Neurol.,  2011, 2011765923
[http://dx.doi.org/10.1155/2011/765923]] [PMID: 21436875] 
[34] 
Goulay, R.; Mena Romo, L.; Hol, E.M.; Dijkhuizen, R.M. From Stroke to Dementia: a Comprehensive Review Exposing Tight Interactions Between Stroke and Amyloid-β Formation. Transl. Stroke Res.,  2019, 11(4), 601-614.
[http://dx.doi.org/10.1007/s12975-019-00755-2] [PMID: 31776837] 
[35] 
Xu, L.; Nirwane, A.; Yao, Y. Basement membrane and blood-brain barrier. Stroke Vasc. Neurol.,  2018, 4(2), 78-82.
[http://dx.doi.org/10.1136/svn-2018-000198] [PMID: 31338215] 
[36] 
Raja, R.; Rosenberg, G.A.; Caprihan, A.  MRI measurements of Blood-Brain Barrier function in dementia: A review of recent studies. Neuropharmacology,  2018, 134(Pt B), 259-271.
[http://dx.doi.org/10.1016/j.neuropharm.2017.10.034] [PMID: 29107626] 
[37] 
Wilhelm, I.; Fazakas, C.; Krizbai, I.A. In vitro models of the blood-brain barrier. Acta Neurobiol. Exp. (Warsz.),  2011, 71(1), 113-128.
[PMID: 21499332] 
[38] 
Hawkins, R.A.; O’Kane, R.L.; Simpson, I.A.; Viña, J.R. Structure of the blood-brain barrier and its role in the transport of amino acids. J. Nutr.,  2006, 136(1)(Suppl.), 218S-226S.
[http://dx.doi.org/10.1093/jn/136.1.218S] [PMID: 16365086] 
[39] 
He, Y.; Yao, Y.; Tsirka, S.E.; Cao, Y. Cell-culture models of the blood-brain barrier. Stroke,  2014, 45(8), 2514-2526.
[http://dx.doi.org/10.1161/STROKEAHA.114.005427] [PMID: 24938839] 
[40] 
Zlokovic, B.V. The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron,  2008, 57(2), 178-201.
[http://dx.doi.org/10.1016/j.neuron.2008.01.003] [PMID: 18215617] 
[41] 
Yao, Y.; Chen, Z-L.; Norris, E.H.; Strickland, S. Astrocytic laminin regulates pericyte differentiation and maintains blood brain barrier integrity. Nat. Commun.,  2014, 5, 3413.
[http://dx.doi.org/10.1038/ncomms4413] [PMID: 24583950] 
[42] 
Janzer, R.C.; Raff, M.C. Astrocytes induce blood-brain barrier properties in endothelial cells. Nature,  1987, 325(6101), 253-257.
[http://dx.doi.org/10.1038/325253a0] [PMID: 3543687] 
[43] 
Bazzoni, G.; Dejana, E. Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis. Physiol. Rev.,  2004, 84(3), 869-901.
[http://dx.doi.org/10.1152/physrev.00035.2003] [PMID: 15269339] 
[44] 
Fenstermacher, J.; Gross, P.; Sposito, N.; Acuff, V.; Pettersen, S.; Gruber, K. Structural and functional variations in capillary systems within the brain. Ann. N. Y. Acad. Sci.,  1988, 529, 21-30.
[http://dx.doi.org/10.1111/j.1749-6632.1988.tb51416.x] [PMID: 3395069] 
[45] 
Keep, R.F.; Andjelkovic, A.V.; Xiang, J.; Stamatovic, S.M.; Antonetti, D.A.; Hua, Y.; Xi, G. Brain endothelial cell junctions after cerebral hemorrhage: Changes, mechanisms and therapeutic targets. J. Cereb. Blood Flow Metab.,  2018, 38(8), 1255-1275.
[http://dx.doi.org/10.1177/0271678X18774666] [PMID: 29737222] 
[46] 
Kniesel, U.; Wolburg, H. Tight junctions of the blood-brain barrier. Cell. Mol. Neurobiol.,  2000, 20(1), 57-76.
[http://dx.doi.org/10.1023/A:1006995910836] [PMID: 10690502] 
[47] 
Yang, C.; Hawkins, K.E.; Doré, S.; Candelario-Jalil, E. Neuroinflammatory mechanisms of blood-brain barrier damage in ischemic stroke. Am. J. Physiol. Cell Physiol.,  2019, 316(2), C135-C153.
[http://dx.doi.org/10.1152/ajpcell.00136.2018] [PMID: 30379577] 
[48] 
Srinivasan, B.; Kolli, A.R.; Esch, M.B.; Abaci, H.E.; Shuler, M.L.; Hickman, J.J. TEER measurement techniques for in vitro barrier model systems. J. Lab. Autom.,  2015, 20(2), 107-126.
[http://dx.doi.org/10.1177/2211068214561025] [PMID: 25586998] 
[49] 
Stamatovic, S.M.; Johnson, A.M.; Keep, R.F.; Andjelkovic, A.V. Junctional proteins of the blood-brain barrier: New insights into function and dysfunction. Tissue Barriers,  2016, 4(1)e1154641
[http://dx.doi.org/10.1080/21688370.2016.1154641]] [PMID: 27141427] 
[50] 
Abbott, N.J.; Patabendige, A.A.K.; Dolman, D.E.M.; Yusof, S.R.; Begley, D.J. Structure and function of the blood-brain barrier. Neurobiol. Dis.,  2010, 37(1), 13-25.
[http://dx.doi.org/10.1016/j.nbd.2009.07.030] [PMID: 19664713] 
[51] 
Kim, S-H.; Turnbull, J.; Guimond, S. Extracellular matrix and cell signalling: the dynamic cooperation of integrin, proteoglycan and growth factor receptor. J. Endocrinol.,  2011, 209(2), 139-151.
[http://dx.doi.org/10.1530/JOE-10-0377] [PMID: 21307119] 
[52] 
Baeten, K.M.; Akassoglou, K. Extracellular matrix and matrix receptors in blood-brain barrier formation and stroke. Dev. Neurobiol.,  2011, 71(11), 1018-1039.
[http://dx.doi.org/10.1002/dneu.20954] [PMID: 21780303] 
[53] 
Hynes, R.O. he extracellular matrix: not just pretty fibrils Science (80-. ), 2009, 326, 1216-1219.
[http://dx.doi.org/10.1126/science.1176009] 
[54] 
Talegaonkar, S.; Mishra, P.R. Intranasal delivery : An approach to bypass the blood brain barrier. Indian J. Pharmacol.,  2004, 36, 140-147.
[55] 
Keep, R.F.; Zhou, N.; Xiang, J.; Andjelkovic, A.V.; Hua, Y.; Xi, G. Vascular disruption and blood-brain barrier dysfunction in intracerebral hemorrhage. Fluids Barriers CNS,  2014, 11, 18.
[http://dx.doi.org/10.1186/2045-8118-11-18] [PMID: 25120903] 
[56] 
Abbott, N.J.; Rönnbäck, L.; Hansson, E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat. Rev. Neurosci.,  2006, 7(1), 41-53.
[http://dx.doi.org/10.1038/nrn1824] [PMID: 16371949] 
[57] 
Deeken, J.F.; Löscher, W. The blood-brain barrier and cancer: transporters, treatment, and Trojan horses. Clin. Cancer Res.,  2007, 13(6), 1663-1674.
[http://dx.doi.org/10.1158/1078-0432.CCR-06-2854] [PMID: 17363519] 
[58] 
Altay, O.; Suzuki, H.; Hasegawa, Y.; Caner, B.; Krafft, P.R.; Fujii, M.; Tang, J.; Zhang, J.H. Isoflurane attenuates blood-brain barrier disruption in ipsilateral hemisphere after subarachnoid hemorrhage in mice. Stroke,  2012, 43(9), 2513-2516.
[http://dx.doi.org/10.1161/STROKEAHA.112.661728] [PMID: 22773559] 
[59] 
Chen, Y.; Zhang, Y.; Tang, J.; Liu, F.; Hu, Q.; Luo, C.; Tang, J.; Feng, H.; Zhang, J.H. Norrin protected blood-brain barrier via frizzled-4/β-catenin pathway after subarachnoid hemorrhage in rats. Stroke,  2015, 46(2), 529-536.
[http://dx.doi.org/10.1161/STROKEAHA.114.007265] [PMID: 25550365] 
[60] 
Pang, J.; Wu, Y.; Peng, J.; Yang, P.; Kuai, L.; Qin, X.; Cao, F.; Sun, X.; Chen, L.; Vitek, M.P.; Jiang, Y. Potential implications of Apolipoprotein E in early brain injury after experimental subarachnoid hemorrhage: Involvement in the modulation of blood-brain barrier integrity. Oncotarget,  2016, 7(35), 56030-56044.
[http://dx.doi.org/10.18632/oncotarget.10821] [PMID: 27463015] 
[61] 
Willis, C.L.L.; Camire, R.B.B.; Brule, S.A.A.; Ray, D.E.E. Partial recovery of the damaged rat blood-brain barrier is mediated by adherens junction complexes, extracellular matrix remodeling and macrophage infiltration following focal astrocyte loss. Neuroscience,  2013, 250, 773-785.
[http://dx.doi.org/10.1016/j.neuroscience.2013.06.061] [PMID: 23845748] 
[62] 
Patino, M.G.; Neiders, M.E.; Andreana, S.; Noble, B.; Cohen, R.E. Collagen: an overview. Implant Dent.,  2002, 11(3), 280-285.
[http://dx.doi.org/10.1097/00008505-200207000-00014] [PMID: 12271567] 
[63] 
Hudson, B.G.; Reeders, S.T.; Tryggvason, K. Type IV collagen: structure, gene organization, and role in human diseases. Molecular basis of Goodpasture and Alport syndromes and diffuse leiomyomatosis. J. Biol. Chem.,  1993, 268(35), 26033-26036.
[PMID: 8253711] 
[64] 
Filie, J.D.; Burbelo, P.D.; Kozak, C.A. Genetic mapping of the alpha 1 and alpha 2 (IV) collagen genes to mouse chromosome 8. Mamm. Genome,  1995, 6(7), 487.
[http://dx.doi.org/10.1007/BF00360662] [PMID: 7579895] 
[65] 
Sado, Y.; Kagawa, M.; Naito, I.; Ueki, Y.; Seki, T.; Momota, R.; Oohashi, T.; Ninomiya, Y. Organization and expression of basement membrane collagen IV genes and their roles in human disorders. J. Biochem.,  1998, 123(5), 767-776.
[http://dx.doi.org/10.1093/oxfordjournals.jbchem.a022003] [PMID: 9562604] 
[66] 
Pöschl, E.; Schlötzer-Schrehardt, U.; Brachvogel, B.; Saito, K.; Ninomiya, Y.; Mayer, U. Collagen IV is essential for basement membrane stability but dispensable for initiation of its assembly during early development. Development,  2004, 131(7), 1619-1628.
[http://dx.doi.org/10.1242/dev.01037] [PMID: 14998921] 
[67] 
Favor, J.; Gloeckner, C.J.; Janik, D.; Klempt, M.; Neuhäuser-Klaus, A.; Pretsch, W.; Schmahl, W.; Quintanilla-Fend, L. Type IV procollagen missense mutations associated with defects of the eye, vascular stability, the brain, kidney function and embryonic or postnatal viability in the mouse, Mus musculus: an extension of the Col4a1 allelic series and the identification of the first two Col4a2 mutant alleles. Genetics,  2007, 175(2), 725-736.
[http://dx.doi.org/10.1534/genetics.106.064733] [PMID: 17179069] 
[68] 
Kuo, D.S.; Labelle-Dumais, C.; Mao, M.; Jeanne, M.; Kauffman, W.B.; Allen, J.; Favor, J.; Gould, D.B. Allelic heterogeneity contributes to variability in ocular dysgenesis, myopathy and brain malformations caused by Col4a1 and Col4a2 mutations. Hum. Mol. Genet.,  2014, 23(7), 1709-1722.
[http://dx.doi.org/10.1093/hmg/ddt560] [PMID: 24203695] 
[69] 
Jeanne, M.; Labelle-Dumais, C.; Jorgensen, J.; Kauffman, W.B.; Mancini, G.M.; Favor, J.; Valant, V.; Greenberg, S.M.; Rosand, J.; Gould, D.B. COL4A2 mutations impair COL4A1 and COL4A2 secretion and cause hemorrhagic stroke. Am. J. Hum. Genet.,  2012, 90(1), 91-101.
[http://dx.doi.org/10.1016/j.ajhg.2011.11.022] [PMID: 22209247] 
[70] 
Hamann, G.F.; Liebetrau, M.; Martens, H.; Burggraf, D.; Kloss, C.U.A.; Bültemeier, G.; Wunderlich, N.; Jäger, G.; Pfefferkorn, T. Microvascular basal lamina injury after experimental focal cerebral ischemia and reperfusion in the rat. J. Cereb. Blood Flow Metab.,  2002, 22(5), 526-533.
[http://dx.doi.org/10.1097/00004647-200205000-00004] [PMID: 11973425] 
[71] 
Härtig, W.; Mages, B.; Aleithe, S.; Nitzsche, B.; Altmann, S.; Barthel, H.; Krueger, M.; Michalski, D. Damaged Neocortical Perineuronal Nets Due to Experimental Focal Cerebral Ischemia in Mice, Rats and Sheep. Front. Integr. Nuerosci.,  2017, 11, 15.
[http://dx.doi.org/10.3389/fnint.2017.00015] [PMID: 28860977] 
[72] 
Milner, R.; Hung, S.; Wang, X.; Spatz, M.; del Zoppo, G.J. The rapid decrease in astrocyte-associated dystroglycan expression by focal cerebral ischemia is protease-dependent. J. Cereb. Blood Flow Metab.,  2008, 28(4), 812-823.
[http://dx.doi.org/10.1038/sj.jcbfm.9600585] [PMID: 18030304] 
[73] 
Pankov, R.; Yamada, K.M. Fibronectin at a glance. J. Cell Sci.,  2002, 115(Pt 20), 3861-3863.
[http://dx.doi.org/10.1242/jcs.00059] [PMID: 12244123] 
[74] 
To, W.S.; Midwood, K.S. Plasma and cellular fibronectin: distinct and independent functions during tissue repair. Fibrogenesis Tissue Repair,  2011, 4, 21.
[http://dx.doi.org/10.1186/1755-1536-4-21] [PMID: 21923916] 
[75] 
Hsiao, C-T.; Cheng, H-W.; Huang, C-M.; Li, H-R.; Ou, M-H.; Huang, J-R.; Khoo, K-H.; Yu, H.W.; Chen, Y-Q.; Wang, Y-K.; Chiou, A.; Kuo, J-C. Fibronectin in cell adhesion and migration via N-glycosylation. Oncotarget,  2017, 8(41), 70653-70668.
[http://dx.doi.org/10.18632/oncotarget.19969] [PMID: 29050309] 
[76] 
Wang, J.; Milner, R. Fibronectin promotes brain capillary endothelial cell survival and proliferation through alpha5beta1 and alphavbeta3 integrins via MAP kinase signalling. J. Neurochem.,  2006, 96(1), 148-159.
[http://dx.doi.org/10.1111/j.1471-4159.2005.03521.x] [PMID: 16269008] 
[77] 
George, E.L.; Georges-Labouesse, E.N.; Patel-King, R.S.; Rayburn, H.; Hynes, R.O. Defects in mesoderm, neural tube and vascular development in mouse embryos lacking fibronectin. Development,  1993, 119(4), 1079-1091.
[PMID: 8306876] 
[78] 
Milner, R.; Campbell, I.L. Developmental regulation of β1 integrins during angiogenesis in the central nervous system. Mol. Cell. Neurosci.,  2002, 20(4), 616-626.
[http://dx.doi.org/10.1006/mcne.2002.1151] [PMID: 12213443] 
[79] 
Sakai, T.; Johnson, K.J.; Murozono, M.; Sakai, K.; Magnuson, M.A.; Wieloch, T.; Cronberg, T.; Isshiki, A.; Erickson, H.P.; Fässler, R. Plasma fibronectin supports neuronal survival and reduces brain injury following transient focal cerebral ischemia but is not essential for skin-wound healing and hemostasis. Nat. Med.,  2001, 7(3), 324-330.
[http://dx.doi.org/10.1038/85471] [PMID: 11231631] 
[80] 
Wang, Y.; Reheman, A.; Spring, C.M.; Kalantari, J.; Marshall, A.H.; Wolberg, A.S.; Gross, P.L.; Weitz, J.I.; Rand, M.L.; Mosher, D.F.; Freedman, J.; Ni, H. Plasma fibronectin supports hemostasis and regulates thrombosis. J. Clin. Invest.,  2014, 124(10), 4281-4293.
[http://dx.doi.org/10.1172/JCI74630] [PMID: 25180602] 
[81] 
Colognato, H.; Yurchenco, P.D. Form and function: the laminin family of heterotrimers. Dev. Dyn.,  2000, 218(2), 213-234.
[http://dx.doi.org/10.1002/(SICI)1097-0177(200006)218:2<213:AID-DVDY1>3.0.CO;2-R] [PMID: 10842354] 
[82] 
Hallmann, R.; Horn, N.; Selg, M.; Wendler, O.; Pausch, F.; Sorokin, L.M. Expression and function of laminins in the embryonic and mature vasculature. Physiol. Rev.,  2005, 85(3), 979-1000.
[http://dx.doi.org/10.1152/physrev.00014.2004] [PMID: 15987800] 
[83] 
Li, S.; Edgar, D.; Fässler, R.; Wadsworth, W.; Yurchenco, P.D. The role of laminin in embryonic cell polarization and tissue organization. Dev. Cell,  2003, 4(5), 613-624.
[http://dx.doi.org/10.1016/S1534-5807(03)00128-X] [PMID: 12737798] 
[84] 
Miner, J.H.; Yurchenco, P.D. Laminin functions in tissue morphogenesis. Annu. Rev. Cell Dev. Biol.,  2004, 20, 255-284.
[http://dx.doi.org/10.1146/annurev.cellbio.20.010403.094555] [PMID: 15473841] 
[85] 
Miner, J.H.; Li, C.; Mudd, J.L.; Go, G.; Sutherland, A.E. Compositional and structural requirements for laminin and basement membranes during mouse embryo implantation and gastrulation. Development,  2004, 131(10), 2247-2256.
[http://dx.doi.org/10.1242/dev.01112] [PMID: 15102706] 
[86] 
Sixt, M.; Engelhardt, B.; Pausch, F.; Hallmann, R.; Wendler, O.; Sorokin, L.M. Endothelial cell laminin isoforms, laminins 8 and 10, play decisive roles in T cell recruitment across the blood-brain barrier in experimental autoimmune encephalomyelitis. J. Cell Biol.,  2001, 153(5), 933-946.
[http://dx.doi.org/10.1083/jcb.153.5.933] [PMID: 11381080] 
[87] 
Sorokin, L.M.; Pausch, F.; Frieser, M.; Kröger, S.; Ohage, E.; Deutzmann, R. Developmental regulation of the laminin alpha5 chain suggests a role in epithelial and endothelial cell maturation. Dev. Biol.,  1997, 189(2), 285-300.
[http://dx.doi.org/10.1006/dbio.1997.8668] [PMID: 9299121] 
[88] 
Jucker, M.; Tian, M.; Norton, D.D.; Sherman, C.; Kusiak, J.W. Laminin alpha 2 is a component of brain capillary basement membrane: reduced expression in dystrophic dy mice. Neuroscience,  1996, 71(4), 1153-1161.
[http://dx.doi.org/10.1016/0306-4522(95)00496-3] [PMID: 8684619] 
[89] 
Sorokin, L.; Girg, W.; Göpfert, T.; Hallmann, R.; Deutzmann, R. Expression of novel 400-kDa laminin chains by mouse and bovine endothelial cells. Eur. J. Biochem.,  1994, 223(2), 603-610.
[http://dx.doi.org/10.1111/j.1432-1033.1994.tb19031.x] [PMID: 8055931] 
[90] 
Tilling, T.; Engelbertz, C.; Decker, S.; Korte, D.; Hüwel, S.; Galla, H-J.J. Expression and adhesive properties of basement membrane proteins in cerebral capillary endothelial cell cultures. Cell Tissue Res.,  2002, 310(1), 19-29.
[http://dx.doi.org/10.1007/s00441-002-0604-1] [PMID: 12242480] 
[91] 
Tilling, T.; Korte, D.; Hoheisel, D.; Galla, H.J. Basement membrane proteins influence brain capillary endothelial barrier function in vitro. J. Neurochem.,  1998, 71(3), 1151-1157.
[http://dx.doi.org/10.1046/j.1471-4159.1998.71031151.x] [PMID: 9721740] 
[92] 
Smyth, N.; Vatansever, H.S.; Murray, P.; Meyer, M.; Frie, C.; Paulsson, M.; Edgar, D. Absence of basement membranes after targeting the LAMC1 gene results in embryonic lethality due to failure of endoderm differentiation. J. Cell Biol.,  1999, 144(1), 151-160.
[http://dx.doi.org/10.1083/jcb.144.1.151] [PMID: 9885251] 
[93] 
Chen, Z-L.L.; Yao, Y.; Norris, E.H.; Kruyer, A.; Jno-Charles, O.; Akhmerov, A.; Strickland, S. Ablation of astrocytic laminin impairs vascular smooth muscle cell function and leads to hemorrhagic stroke. J. Cell Biol.,  2013, 202(2), 381-395.
[http://dx.doi.org/10.1083/jcb.201212032] [PMID: 23857767] 
[94] 
Thyboll, J.; Kortesmaa, J.; Cao, R.; Soininen, R.; Wang, L.; Iivanainen, A.; Sorokin, L.; Risling, M.; Cao, Y.; Tryggvason, K. Deletion of the laminin alpha4 chain leads to impaired microvessel maturation. Mol. Cell. Biol.,  2002, 22(4), 1194-1202.
[http://dx.doi.org/10.1128/MCB.22.4.1194-1202.2002] [PMID: 11809810] 
[95] 
Halfter, W.; Dong, S.; Yip, Y-P.; Willem, M.; Mayer, U. A critical function of the pial basement membrane in cortical histogenesis. J. Neurosci.,  2002, 22(14), 6029-6040.
[http://dx.doi.org/10.1523/JNEUROSCI.22-14-06029.2002] [PMID: 12122064] 
[96] 
Knöll, R.; Postel, R.; Wang, J.; Krätzner, R.; Hennecke, G.; Vacaru, A.M.; Vakeel, P.; Schubert, C.; Murthy, K.; Rana, B.K.; Kube, D.; Knöll, G.; Schäfer, K.; Hayashi, T.; Holm, T.; Kimura, A.; Schork, N.; Toliat, M.R.; Nürnberg, P.; Schultheiss, H-P.; Schaper, W.; Schaper, J.; Bos, E.; Den Hertog, J.; van Eeden, F.J.M.; Peters, P.J.; Hasenfuss, G.; Chien, K.R.; Bakkers, J. Laminin-alpha4 and integrin-linked kinase mutations cause human cardiomyopathy via simultaneous defects in cardiomyocytes and endothelial cells. Circulation,  2007, 116(5), 515-525.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.107.689984] [PMID: 17646580] 
[97] 
Miyagoe, Y.; Hanaoka, K.; Nonaka, I.; Hayasaka, M.; Nabeshima, Y.; Arahata, K.; Nabeshima, Y.; Takeda, S. Laminin alpha2 chain-null mutant mice by targeted disruption of the Lama2 gene: a new model of merosin (laminin 2)-deficient congenital muscular dystrophy. FEBS Lett.,  1997, 415(1), 33-39.
[http://dx.doi.org/10.1016/S0014-5793(97)01007-7] [PMID: 9326364] 
[98] 
Miner, J.H.; Cunningham, J.; Sanes, J.R. Roles for laminin in embryogenesis: exencephaly, syndactyly, and placentopathy in mice lacking the laminin alpha5 chain. J. Cell Biol.,  1998, 143(6), 1713-1723.
[http://dx.doi.org/10.1083/jcb.143.6.1713] [PMID: 9852162] 
[99] 
Yousif, L.F.; Di Russo, J.; Sorokin, L. Laminin isoforms in endothelial and perivascular basement membranes. Cell Adhes. Migr.,  2013, 7(1), 101-110.
[http://dx.doi.org/10.4161/cam.22680] [PMID: 23263631] 
[100] 
Edwards, D.N.; Bix, G.J. Roles of blood-brain barrier integrins and extracellular matrix in stroke. Am. J. Physiol. Cell Physiol.,  2019, 316(2), C252-C263.
[http://dx.doi.org/10.1152/ajpcell.00151.2018] [PMID: 30462535] 
[101] 
Jucker, M.; Bialobok, P.; Kleinman, H.K.; Walker, L.C.; Hagg, T.; Ingram, D.K. Laminin-like and laminin-binding protein-like immunoreactive astrocytes in rat hippocampus after transient ischemia. Antibody to laminin-binding protein is a sensitive marker of neural injury and degeneration. Ann. N. Y. Acad. Sci.,  1993, 679, 245-252.
[http://dx.doi.org/10.1111/j.1749-6632.1993.tb18304.x] [PMID: 8512187] 
[102] 
Szabó, A.; Kálmán, M. Disappearance of the post-lesional laminin immunopositivity of brain vessels is parallel with the formation of gliovascular junctions and common basal lamina. A double-labelling immunohistochemical study. Neuropathol. Appl. Neurobiol.,  2004, 30(2), 169-177.
[http://dx.doi.org/10.1046/j.0305-1846.2003.00524.x] [PMID: 15043714] 
[103] 
Li, L.; Liu, F.; Welser-Alves, J.V.; McCullough, L.D.; Milner, R. Upregulation of fibronectin and the α5β1 and αvβ3 integrins on blood vessels within the cerebral ischemic penumbra. Exp. Neurol.,  2012, 233(1), 283-291.
[http://dx.doi.org/10.1016/j.expneurol.2011.10.017] [PMID: 22056225] 
[104] 
Fujioka, T.; Kaneko, N.; Ajioka, I.; Nakaguchi, K.; Omata, T.; Ohba, H.; Fässler, R.; García-Verdugo, J.M.; Sekiguchi, K.; Matsukawa, N.; Sawamoto, K. β1 integrin signaling promotes neuronal migration along vascular scaffolds in the post-stroke brain. EBioMedicine,  2017, 16, 195-203.
[http://dx.doi.org/10.1016/j.ebiom.2017.01.005] [PMID: 28153772] 
[105] 
Gautam, J.; Cao, Y.; Yao, Y. Pericytic Laminin Maintains Blood-Brain Barrier Integrity in an Age-Dependent Manner. Transl. Stroke Res.,  2020, 11(2), 228-242.
[http://dx.doi.org/10.1007/s12975-019-00709-8] [PMID: 31292838] 
[106] 
Gautam, J.; Miner, J.H.; Yao, Y. Loss of Endothelial Laminin α5 Exacerbates Hemorrhagic Brain Injury. Transl. Stroke Res.,  2019, 10(6), 705-718.
[http://dx.doi.org/10.1007/s12975-019-0688-5] [PMID: 30693425] 
[107] 
Pákáski, M.; Kása, P.; Joó, F.; Wolff, J.R. Cerebral endothelial cell-derived laminin promotes the outgrowth of neurites in CNS neuronal cultures. Int. J. Dev. Neurosci.,  1990, 8(2), 193-198.
[http://dx.doi.org/10.1016/0736-5748(90)90010-Y] [PMID: 2327290] 
[108] 
Hatakeyama, M.; Ninomiya, I.; Kanazawa, M. Angiogenesis and neuronal remodeling after ischemic stroke. Neural Regen. Res.,  2020, 15(1), 16-19.
[http://dx.doi.org/10.4103/1673-5374.264442] [PMID: 31535636] 
[109] 
Grimpe, B.; Probst, J.C.; Hager, G. Suppression of nidogen-1 translation by antisense targeting affects the adhesive properties of cultured astrocytes. Glia,  1999, 28(2), 138-149.
[http://dx.doi.org/10.1002/(SICI)1098-1136(199911)28:2<138:AID-GLIA5>3.0.CO;2-8] [PMID: 10533057] 
[110] 
Kang, S.H.; Kramer, J.M. Nidogen is nonessential and not required for normal type IV collagen localization in Caenorhabditis elegans. Mol. Biol. Cell,  2000, 11(11), 3911-3923.
[http://dx.doi.org/10.1091/mbc.11.11.3911] [PMID: 11071916] 
[111] 
Dong, L.; Chen, Y.; Lewis, M.; Hsieh, J-C.; Reing, J.; Chaillet, J.R.; Howell, C.Y.; Melhem, M.; Inoue, S.; Kuszak, J.R.; DeGeest, K.; Chung, A.E. Neurologic defects and selective disruption of basement membranes in mice lacking entactin-1/nidogen-1. Lab. Invest.,  2002, 82(12), 1617-1630.
[http://dx.doi.org/10.1097/01.LAB.0000042240.52093.0F] [PMID: 12480912] 
[112] 
Murshed, M.; Smyth, N.; Miosge, N.; Karolat, J.; Krieg, T.; Paulsson, M.; Nischt, R. The absence of nidogen 1 does not affect murine basement membrane formation. Mol. Cell. Biol.,  2000, 20(18), 7007-7012.
[http://dx.doi.org/10.1128/MCB.20.18.7007-7012.2000] [PMID: 10958695] 
[113] 
Mokkapati, S.; Baranowsky, A.; Mirancea, N.; Smyth, N.; Breitkreutz, D.; Nischt, R. Basement membranes in skin are differently affected by lack of nidogen 1 and 2. J. Invest. Dermatol.,  2008, 128(9), 2259-2267.
[http://dx.doi.org/10.1038/jid.2008.65] [PMID: 18356808] 
[114] 
Böse, K.; Nischt, R.; Page, A.; Bader, B.L.; Paulsson, M.; Smyth, N. Loss of nidogen-1 and -2 results in syndactyly and changes in limb development. J. Biol. Chem.,  2006, 281(51), 39620-39629.
[http://dx.doi.org/10.1074/jbc.M607886200] [PMID: 17023412] 
[115] 
Bader, B.L.; Smyth, N.; Nedbal, S.; Miosge, N.; Baranowsky, A.; Mokkapati, S.; Murshed, M.; Nischt, R. Compound genetic ablation of nidogen 1 and 2 causes basement membrane defects and perinatal lethality in mice. Mol. Cell. Biol.,  2005, 25(15), 6846-6856.
[http://dx.doi.org/10.1128/MCB.25.15.6846-6856.2005] [PMID: 16024816] 
[116] 
Schymeinsky, J.; Nedbal, S.; Miosge, N.; Pöschl, E.; Rao, C.; Beier, D.R.; Skarnes, W.C.; Timpl, R.; Bader, B.L. Gene structure and functional analysis of the mouse nidogen-2 gene: nidogen-2 is not essential for basement membrane formation in mice. Mol. Cell. Biol.,  2002, 22(19), 6820-6830.
[http://dx.doi.org/10.1128/MCB.22.19.6820-6830.2002] [PMID: 12215539] 
[117] 
Miosge, N.; Sasaki, T.; Timpl, R. Evidence of nidogen-2 compensation for nidogen-1 deficiency in transgenic mice. Matrix Biol.,  2002, 21(7), 611-621.
[http://dx.doi.org/10.1016/S0945-053X(02)00070-7] [PMID: 12475645] 
[118] 
Agrawal, S.; Anderson, P.; Durbeej, M.; van Rooijen, N.; Ivars, F.; Opdenakker, G.; Sorokin, L.M. Dystroglycan is selectively cleaved at the parenchymal basement membrane at sites of leukocyte extravasation in experimental autoimmune encephalomyelitis. J. Exp. Med.,  2006, 203(4), 1007-1019.
[http://dx.doi.org/10.1084/jem.20051342] [PMID: 16585265] 
[119] 
Knox, S.M.; Whitelock, J.M. Perlecan: how does one molecule do so many things? Cell. Mol. Life Sci.,  2006, 63(21), 2435-2445.
[http://dx.doi.org/10.1007/s00018-006-6162-z] [PMID: 16952056] 
[120] 
Whitelock, J.M.; Melrose, J.; Iozzo, R.V. Diverse cell signaling events modulated by perlecan. Biochemistry,  2008, 47(43), 11174-11183.
[http://dx.doi.org/10.1021/bi8013938] [PMID: 18826258] 
[121] 
Costell, M.; Sasaki, T.; Mann, K.; Yamada, Y.; Timpl, R. Structural characterization of recombinant domain II of the basement membrane proteoglycan perlecan. FEBS Lett.,  1996, 396(2-3), 127-131.
[http://dx.doi.org/10.1016/0014-5793(96)01082-4] [PMID: 8914972] 
[122] 
Dolan, M.; Horchar, T.; Rigatti, B.; Hassell, J.R. Identification of sites in domain I of perlecan that regulate heparan sulfate synthesis. J. Biol. Chem.,  1997, 272(7), 4316-4322.
[http://dx.doi.org/10.1074/jbc.272.7.4316] [PMID: 9020150] 
[123] 
Hopf, M.; Göhring, W.; Mann, K.; Timpl, R. Mapping of binding sites for nidogens, fibulin-2, fibronectin and heparin to different IG modules of perlecan. J. Mol. Biol.,  2001, 311(3), 529-541.
[http://dx.doi.org/10.1006/jmbi.2001.4878] [PMID: 11493006] 
[124] 
Handler, M.; Yurchenco, P.D.; Iozzo, R.V. Developmental expression of perlecan during murine embryogenesis. Dev. Dyn.,  1997, 210(2), 130-145.
[http://dx.doi.org/10.1002/(SICI)1097-0177(199710)210:2<130:AID-AJA6>3.0.CO;2-H] [PMID: 9337134] 
[125] 
Costell, M.; Gustafsson, E.; Aszódi, A.; Mörgelin, M.; Bloch, W.; Hunziker, E.; Addicks, K.; Timpl, R.; Fässler, R. Perlecan maintains the integrity of cartilage and some basement membranes. J. Cell Biol.,  1999, 147(5), 1109-1122.
[http://dx.doi.org/10.1083/jcb.147.5.1109] [PMID: 10579729] 
[126] 
Ford-Perriss, M.; Turner, K.; Guimond, S.; Apedaile, A.; Haubeck, H-D.; Turnbull, J.; Murphy, M. Localisation of specific heparan sulfate proteoglycans during the proliferative phase of brain development. Dev. Dyn.,  2003, 227(2), 170-184.
[http://dx.doi.org/10.1002/dvdy.10298] [PMID: 12761845] 
[127] 
Clarke, D.N.; Al Ahmad, A.; Lee, B.; Parham, C.; Auckland, L.; Fertala, A.; Kahle, M.; Shaw, C.S.; Roberts, J.; Bix, G.J. Perlecan Domain V induces VEGf secretion in brain endothelial cells through integrin α5β1 and ERK-dependent signaling pathways. PLoS One,  2012, 7(9)e45257
[http://dx.doi.org/10.1371/journal.pone.0045257]] [PMID: 23028886] 
[128] 
Li, L.; Welser, J.V.; Milner, R. Absence of the alpha v beta 3 integrin dictates the time-course of angiogenesis in the hypoxic central nervous system: accelerated endothelial proliferation correlates with compensatory increases in alpha 5 beta 1 integrin expression. J. Cereb. Blood Flow Metab.,  2010, 30(5), 1031-1043.
[http://dx.doi.org/10.1038/jcbfm.2009.276] [PMID: 20087368] 
[129] 
Trout, A.L.; Kahle, M.P.; Roberts, J.M.; Marcelo, A.; de Hoog, L.; Boychuk, J.A.; Grupke, S.L.; Berretta, A.; Gowing, E.K.; Boychuk, C.R.; Gorman, A.A.; Edwards, D.N.; Rutkai, I.; Biose, I.J.; Ishibashi-Ueda, H.; Ihara, M.; Smith, B.N.; Clarkson, A.N.; Bix, G.J. Perlecan Domain-V Enhances Neurogenic Brain Repair After Stroke in Mice. Transl. Stroke Res., 2020. Epub ahead of print
[http://dx.doi.org/10.1007/s12975-020-00800-5] [PMID: 32253702] 
[130] 
Lee, B.; Clarke, D.; Al Ahmad, A.; Kahle, M.; Parham, C.; Auckland, L.; Shaw, C.; Fidanboylu, M.; Orr, A.W.; Ogunshola, O.; Fertala, A.; Thomas, S.A.; Bix, G.J. Perlecan domain V is neuroprotective and proangiogenic following ischemic stroke in rodents. J. Clin. Invest.,  2011, 121(8), 3005-3023.
[http://dx.doi.org/10.1172/JCI46358] [PMID: 21747167] 
[131] 
Roberts, J.; Kahle, M.P.; Bix, G.J. Perlecan and the blood-brain barrier: beneficial proteolysis? Front. Pharmacol.,  2012, 3, 155.
[http://dx.doi.org/10.3389/fphar.2012.00155] [PMID: 22936915] 
[132] 
Al-Ahmad, A.J.; Lee, B.; Saini, M.; Bix, G.J. Perlecan domain V modulates astrogliosis in vitro and after focal cerebral ischemia through multiple receptors and increased nerve growth factor release. Glia,  2011, 59(12), 1822-1840.
[http://dx.doi.org/10.1002/glia.21227] [PMID: 21850672] 
[133] 
Baumann, E.; Preston, E.; Slinn, J.; Stanimirovic, D. Post-ischemic hypothermia attenuates loss of the vascular basement membrane proteins, agrin and SPARC, and the blood-brain barrier disruption after global cerebral ischemia. Brain Res.,  2009, 1269, 185-197.
[http://dx.doi.org/10.1016/j.brainres.2009.02.062] [PMID: 19285050] 
[134] 
Steiner, E.; Enzmann, G.U.; Lyck, R.; Lin, S.; Rüegg, M.A.; Kröger, S.; Engelhardt, B. The heparan sulfate proteoglycan agrin contributes to barrier properties of mouse brain endothelial cells by stabilizing adherens junctions. Cell Tissue Res.,  2014, 358(2), 465-479.
[http://dx.doi.org/10.1007/s00441-014-1969-7] [PMID: 25107608] 
[135] 
Gautam, M.; Noakes, P.G.; Moscoso, L.; Rupp, F.; Scheller, R.H.; Merlie, J.P.; Sanes, J.R. Defective neuromuscular synaptogenesis in agrin-deficient mutant mice. Cell,  1996, 85(4), 525-535.
[http://dx.doi.org/10.1016/S0092-8674(00)81253-2] [PMID: 8653788] 
[136] 
Barber, A.J.; Lieth, E. Agrin accumulates in the brain microvascular basal lamina during development of the blood-brain barrier. Dev. Dyn.,  1997, 208(1), 62-74.
[http://dx.doi.org/10.1002/(SICI)1097-0177(199701)208:1<62:AID-AJA6>3.0.CO;2-#] [PMID: 8989521] 
[137] 
Gesemann, M.; Brancaccio, A.; Schumacher, B.; Ruegg, M.A. Agrin is a high-affinity binding protein of dystroglycan in non-muscle tissue. J. Biol. Chem.,  1998, 273(1), 600-605.
[http://dx.doi.org/10.1074/jbc.273.1.600] [PMID: 9417121] 
[138] 
Rascher, G.; Fischmann, A.; Kröger, S.; Duffner, F.; Grote, E-H.; Wolburg, H. Extracellular matrix and the blood-brain barrier in glioblastoma multiforme: spatial segregation of tenascin and agrin. Acta Neuropathol.,  2002, 104(1), 85-91.
[http://dx.doi.org/10.1007/s00401-002-0524-x] [PMID: 12070669] 
[139] 
Noell, S.; Fallier-Becker, P.; Deutsch, U.; Mack, A.F.; Wolburg, H. Agrin defines polarized distribution of orthogonal arrays of particles in astrocytes. Cell Tissue Res.,  2009, 337(2), 185-195.
[http://dx.doi.org/10.1007/s00441-009-0812-z] [PMID: 19449033] 
[140] 
del Zoppo, G.J. Aging and the neurovascular unit. Ann. N. Y. Acad. Sci.,  2012, 1268, 127-133.
[http://dx.doi.org/10.1111/j.1749-6632.2012.06686.x] [PMID: 22994231] 
[141] 
Mäe, M.; Armulik, A.; Betsholtz, C. Getting to know the cast - cellular interactions and signaling at the neurovascular unit. Curr. Pharm. Des.,  2011, 17(26), 2750-2754.
[http://dx.doi.org/10.2174/138161211797440113] [PMID: 21827409] 
[142] 
Ronaldson, P.T.; Davis, T.P. Blood-brain barrier integrity and glial support: mechanisms that can be targeted for novel therapeutic approaches in stroke. Curr. Pharm. Des.,  2012, 18(25), 3624-3644.
[http://dx.doi.org/10.2174/138161212802002625] [PMID: 22574987] 
[143] 
Stanimirovic, D.B.; Friedman, A. Pathophysiology of the neurovascular unit: disease cause or consequence? J. Cereb. Blood Flow Metab.,  2012, 32(7), 1207-1221.
[http://dx.doi.org/10.1038/jcbfm.2012.25] [PMID: 22395208] 
[144] 
Zonta, M.; Angulo, M.C.; Gobbo, S.; Rosengarten, B.; Hossmann, K-A.; Pozzan, T.; Carmignoto, G. Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation. Nat. Neurosci.,  2003, 6(1), 43-50.
[http://dx.doi.org/10.1038/nn980] [PMID: 12469126] 
[145] 
Armulik, A.; Genové, G.; Betsholtz, C. Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev. Cell,  2011, 21(2), 193-215.
[http://dx.doi.org/10.1016/j.devcel.2011.07.001] [PMID: 21839917] 
[146] 
Armulik, A.; Genové, G.; Mäe, M.; Nisancioglu, M.H.; Wallgard, E.; Niaudet, C.; He, L.; Norlin, J.; Lindblom, P.; Strittmatter, K.; Johansson, B.R.; Betsholtz, C. Pericytes regulate the blood-brain barrier. Nature,  2010, 468(7323), 557-561.
[http://dx.doi.org/10.1038/nature09522] [PMID: 20944627] 
[147] 
Bergers, G.; Song, S. The role of pericytes in blood-vessel formation and maintenance. Neuro-oncol.,  2005, 7(4), 452-464.
[http://dx.doi.org/10.1215/S1152851705000232] [PMID: 16212810] 
[148] 
Winkler, E.A.; Bell, R.D.; Zlokovic, B.V. Central nervous system pericytes in health and disease. Nat. Neurosci.,  2011, 14(11), 1398-1405.
[http://dx.doi.org/10.1038/nn.2946] [PMID: 22030551] 
[149] 
Alvarez, J.I.; Katayama, T.; Prat, A. Glial influence on the blood brain barrier. Glia,  2013, 61(12), 1939-1958.
[http://dx.doi.org/10.1002/glia.22575] [PMID: 24123158] 
[150] 
Hamby, M.E.; Sofroniew, M.V. Reactive astrocytes as therapeutic targets for CNS disorders. Neurotherapeutics,  2010, 7(4), 494-506.
[http://dx.doi.org/10.1016/j.nurt.2010.07.003] [PMID: 20880511] 
[151] 
Maragakis, N.J.; Rothstein, J.D. Mechanisms of Disease: astrocytes in neurodegenerative disease. Nat. Clin. Pract. Neurol.,  2006, 2(12), 679-689.
[http://dx.doi.org/10.1038/ncpneuro0355] [PMID: 17117171] 
[152] 
Wong, A.D.; Ye, M.; Levy, A.F.; Rothstein, J.D.; Bergles, D.E.; Searson, P.C. The blood-brain barrier: an engineering perspective. Front. Neuroeng.,  2013, 6, 7.
[http://dx.doi.org/10.3389/fneng.2013.00007] [PMID: 24009582] 
[153] 
Daneman, R.; Zhou, L.; Kebede, A.A.; Barres, B.A. Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature,  2010, 468(7323), 562-566.
[http://dx.doi.org/10.1038/nature09513] [PMID: 20944625] 
[154] 
Bai, Y.; Zhu, X.; Chao, J.; Zhang, Y.; Qian, C.; Li, P.; Liu, D.; Han, B.; Zhao, L.; Zhang, J.; Buch, S.; Teng, G.; Hu, G.; Yao, H. Pericytes contribute to the disruption of the cerebral endothelial barrier via increasing VEGF expression: implications for stroke. PLoS One,  2015, 10(4)e0124362
[http://dx.doi.org/10.1371/journal.pone.0124362] [PMID: 25884837] 
[155] 
Bell, R.D.; Winkler, E.A.; Sagare, A.P.; Singh, I.; LaRue, B.; Deane, R.; Zlokovic, B.V. Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging. Neuron,  2010, 68(3), 409-427.
[http://dx.doi.org/10.1016/j.neuron.2010.09.043] [PMID: 21040844] 
[156] 
Duz, B.; Oztas, E.; Erginay, T.; Erdogan, E.; Gonul, E. The effect of moderate hypothermia in acute ischemic stroke on pericyte migration: an ultrastructural study. Cryobiology,  2007, 55(3), 279-284.
[http://dx.doi.org/10.1016/j.cryobiol.2007.08.009] [PMID: 17923122] 
[157] 
Fukuda, S.; Fini, C.A.; Mabuchi, T.; Koziol, J.A.; Eggleston, L.L., Jr; del Zoppo, G.J. Focal cerebral ischemia induces active proteases that degrade microvascular matrix. Stroke,  2004, 35(4), 998-1004.
[http://dx.doi.org/10.1161/01.STR.0000119383.76447.05] [PMID: 15001799] 
[158] 
Gonul, E.; Duz, B.; Kahraman, S.; Kayali, H.; Kubar, A.; Timurkaynak, E. Early pericyte response to brain hypoxia in cats: an ultrastructural study. Microvasc. Res.,  2002, 64(1), 116-119.
[http://dx.doi.org/10.1006/mvre.2002.2413] [PMID: 12074637] 
[159] 
Yamagishi, S.; Yonekura, H.; Yamamoto, Y.; Fujimori, H.; Sakurai, S.; Tanaka, N.; Yamamoto, H. Vascular endothelial growth factor acts as a pericyte mitogen under hypoxic conditions. Lab. Invest.,  1999, 79(4), 501-509.
[PMID: 10212003] 
[160] 
Yang, S.; Jin, H.; Zhu, Y.; Wan, Y.; Opoku, E.N.; Zhu, L.; Hu, B. Diverse Functions and Mechanisms of Pericytes in Ischemic Stroke. Curr. Neuropharmacol.,  2017, 15(6), 892-905.
[http://dx.doi.org/10.2174/1570159X15666170112170226] [PMID: 28088914] 
[161] 
Villaseñor, R.; Kuennecke, B.; Ozmen, L.; Ammann, M.; Kugler, C.; Grüninger, F.; Loetscher, H.; Freskgård, P-O.; Collin, L. Region-specific permeability of the blood-brain barrier upon pericyte loss. J. Cereb. Blood Flow Metab.,  2017, 37(12), 3683-3694.
[http://dx.doi.org/10.1177/0271678X17697340] [PMID: 28273726] 
[162] 
Liu, L.; Fujimoto, M.; Kawakita, F.; Nakano, F.; Imanaka-Yoshida, K.; Yoshida, T.; Suzuki, H. Anti-Vascular Endothelial Growth Factor Treatment Suppresses Early Brain Injury After Subarachnoid Hemorrhage in Mice. Mol. Neurobiol.,  2016, 53(7), 4529-4538.
[http://dx.doi.org/10.1007/s12035-015-9386-9] [PMID: 26289408] 
[163] 
Argaw, A.T.; Asp, L.; Zhang, J.; Navrazhina, K.; Pham, T.; Mariani, J.N.; Mahase, S.; Dutta, D.J.; Seto, J.; Kramer, E.G.; Ferrara, N.; Sofroniew, M.V.; John, G.R. Astrocyte-derived VEGF-A drives blood-brain barrier disruption in CNS inflammatory disease. J. Clin. Invest.,  2012, 122(7), 2454-2468.
[http://dx.doi.org/10.1172/JCI60842] [PMID: 22653056] 
[164] 
Lee, S-C.; Lee, K-Y.; Kim, Y-J.; Kim, S.H.; Koh, S-H.; Lee, Y.J. Serum VEGF levels in acute ischaemic strokes are correlated with long-term prognosis. Eur. J. Neurol.,  2010, 17(1), 45-51.
[http://dx.doi.org/10.1111/j.1468-1331.2009.02731.x] [PMID: 19566899] 
[165] 
Sobrino, T.; Arias, S.; Rodríguez-González, R.; Brea, D.; Silva, Y.; de la Ossa, N.P.; Agulla, J.; Blanco, M.; Pumar, J.M.; Serena, J.; Dávalos, A.; Castillo, J. High serum levels of growth factors are associated with good outcome in intracerebral hemorrhage. J. Cereb. Blood Flow Metab.,  2009, 29(12), 1968-1974.
[http://dx.doi.org/10.1038/jcbfm.2009.182] [PMID: 19756022] 
[166] 
Yu, S.; Yao, S.; Wen, Y.; Wang, Y.; Wang, H.; Xu, Q. Angiogenic microspheres promote neural regeneration and motor function recovery after spinal cord injury in rats. Sci. Rep.,  2016, 6, 33428.
[http://dx.doi.org/10.1038/srep33428] [PMID: 27641997] 
[167] 
Hayashi, Y.; Nomura, M.; Yamagishi, S.; Harada, S.; Yamashita, J.; Yamamoto, H. Induction of various blood-brain barrier properties in non-neural endothelial cells by close apposition to co-cultured astrocytes. Glia,  1997, 19(1), 13-26.
[http://dx.doi.org/10.1002/(SICI)1098-1136(199701)19:1<13:AID-GLIA2>3.0.CO;2-B] [PMID: 8989564] 
[168] 
Sobue, K.; Yamamoto, N.; Yoneda, K.; Hodgson, M.E.; Yamashiro, K.; Tsuruoka, N.; Tsuda, T.; Katsuya, H.; Miura, Y.; Asai, K.; Kato, T. Induction of blood-brain barrier properties in immortalized bovine brain endothelial cells by astrocytic factors. Neurosci. Res.,  1999, 35(2), 155-164.
[http://dx.doi.org/10.1016/S0168-0102(99)00079-6] [PMID: 10616919] 
[169] 
Ahsan, M.S.; Yamazaki, M.; Maruyama, S.; Kobayashi, T.; Ida-Yonemochi, H.; Hasegawa, M.; Henry Ademola, A.; Cheng, J.; Saku, T. Differential expression of perlecan receptors, α-dystroglycan and integrin β1, before and after invasion of oral squamous cell carcinoma. J. Oral Pathol. Med.,  2011, 40(7), 552-559.
[http://dx.doi.org/10.1111/j.1600-0714.2010.00990.x] [PMID: 21198869] 
[170] 
Li, W.; Pan, R.; Qi, Z.; Liu, K.J. Current progress in searching for clinically useful biomarkers of blood-brain barrier damage following cerebral ischemia. Brain Circ.,  2018, 4(4), 145-152.
[http://dx.doi.org/10.4103/bc.bc_11_18] [PMID: 30693340] 
[171] 
Sofroniew, M.V.; Vinters, H.V. Astrocytes: biology and pathology. Acta Neuropathol.,  2010, 119(1), 7-35.
[http://dx.doi.org/10.1007/s00401-009-0619-8] [PMID: 20012068] 
[172] 
Montgomery, D.L. Astrocytes: form, functions, and roles in disease. Vet. Pathol.,  1994, 31(2), 145-167.
[http://dx.doi.org/10.1177/030098589403100201] [PMID: 8203078] 
[173] 
Willis, C.L.; Nolan, C.C.; Reith, S.N.; Lister, T.; Prior, M.J.W.; Guerin, C.J.; Mavroudis, G.; Ray, D.E. Focal astrocyte loss is followed by microvascular damage, with subsequent repair of the blood-brain barrier in the apparent absence of direct astrocytic contact. Glia,  2004, 45(4), 325-337.
[http://dx.doi.org/10.1002/glia.10333] [PMID: 14966864] 
[174] 
Nawashiro, H.; Brenner, M.; Fukui, S.; Shima, K.; Hallenbeck, J.M. High susceptibility to cerebral ischemia in GFAP-null mice. J. Cereb. Blood Flow Metab.,  2000, 20(7), 1040-1044.
[http://dx.doi.org/10.1097/00004647-200007000-00003] [PMID: 10908037] 
[175] 
Argaw, A.T.; Gurfein, B.T.; Zhang, Y.; Zameer, A.; John, G.R. VEGF-mediated disruption of endothelial CLN-5 promotes blood-brain barrier breakdown. Proc. Natl. Acad. Sci. USA,  2009, 106(6), 1977-1982.
[http://dx.doi.org/10.1073/pnas.0808698106] [PMID: 19174516] 
[176] 
Argaw, A.T.; Zhang, Y.; Snyder, B.J.; Zhao, M-L.; Kopp, N.; Lee, S.C.; Raine, C.S.; Brosnan, C.F.; John, G.R. IL-1β regulates blood-brain barrier permeability via reactivation of the hypoxia-angiogenesis program. J. Immunol.,  2006, 177(8), 5574-5584.
[http://dx.doi.org/10.4049/jimmunol.177.8.5574] [PMID: 17015745] 
[177] 
Dobrogowska, D.H.; Lossinsky, A.S.; Tarnawski, M.; Vorbrodt, A.W. Increased blood-brain barrier permeability and endothelial abnormalities induced by vascular endothelial growth factor. J. Neurocytol.,  1998, 27(3), 163-173.
[http://dx.doi.org/10.1023/A:1006907608230] [PMID: 10640176] 
[178] 
Proescholdt, M.A.; Jacobson, S.; Tresser, N.; Oldfield, E.H.; Merrill, M.J. Vascular endothelial growth factor is expressed in multiple sclerosis plaques and can induce inflammatory lesions in experimental allergic encephalomyelitis rats. J. Neuropathol. Exp. Neurol.,  2002, 61(10), 914-925.
[http://dx.doi.org/10.1093/jnen/61.10.914] [PMID: 12387457] 
[179] 
Powell, D.W. Barrier function of epithelia. Am. J. Physiol.,  1981, 241(4), G275-G288.
[PMID: 7032321] 
[180] 
Crone, C.; Christensen, O. Electrical resistance of a capillary endothelium. J. Gen. Physiol.,  1981, 77(4), 349-371.
[http://dx.doi.org/10.1085/jgp.77.4.349] [PMID: 7241087] 
[181] 
Deli, M.A.; Abrahám, C.S.; Kataoka, Y.; Niwa, M. Permeability studies on in vitro blood-brain barrier models: physiology, pathology, and pharmacology. Cell. Mol. Neurobiol.,  2005, 25(1), 59-127.
[http://dx.doi.org/10.1007/s10571-004-1377-8] [PMID: 15962509] 
[182] 
Daniels, B.P.; Cruz-Orengo, L.; Pasieka, T.J.; Couraud, P-O.; Romero, I.A.; Weksler, B.; Cooper, J.A.; Doering, T.L.; Klein, R.S. Immortalized human cerebral microvascular endothelial cells maintain the properties of primary cells in an in vitro model of immune migration across the blood brain barrier. J. Neurosci. Methods,  2013, 212(1), 173-179.
[http://dx.doi.org/10.1016/j.jneumeth.2012.10.001] [PMID: 23068604] 
[183] 
Neuhaus, J.; Risau, W.; Wolburg, H. Induction of blood-brain barrier characteristics in bovine brain endothelial cells by rat astroglial cells in transfilter coculture. Ann. N. Y. Acad. Sci.,  1991, 633, 578-580.
[http://dx.doi.org/10.1111/j.1749-6632.1991.tb15667.x] [PMID: 1789585] 
[184] 
Tao-Cheng, J.H.; Nagy, Z.; Brightman, M.W. Tight junctions of brain endothelium in vitro are enhanced by astroglia. J. Neurosci.,  1987, 7(10), 3293-3299.
[http://dx.doi.org/10.1523/JNEUROSCI.07-10-03293.1987] [PMID: 3668629] 
[185] 
Lippmann, E.S.; Azarin, S.M.; Kay, J.E.; Nessler, R.A.; Wilson, H.K.; Al-Ahmad, A.; Palecek, S.P.; Shusta, E.V. Derivation of blood-brain barrier endothelial cells from human pluripotent stem cells. Nat. Biotechnol.,  2012, 30(8), 783-791.
[http://dx.doi.org/10.1038/nbt.2247] [PMID: 22729031] 
[186] 
Chen, S.; Einspanier, R.; Schoen, J. Transepithelial electrical resistance (TEER): a functional parameter to monitor the quality of oviduct epithelial cells cultured on filter supports. Histochem. Cell Biol.,  2015, 144(5), 509-515.
[http://dx.doi.org/10.1007/s00418-015-1351-1] [PMID: 26223877] 
[187] 
Watson, P.M.D.; Paterson, J.C.; Thom, G.; Ginman, U.; Lundquist, S.; Webster, C.I. Modelling the endothelial blood-CNS barriers: a method for the production of robust in vitro models of the rat blood-brain barrier and blood-spinal cord barrier. BMC Neurosci.,  2013, 14, 59.
[http://dx.doi.org/10.1186/1471-2202-14-59] [PMID: 23773766] 
[188] 
Anderson, J.M. Molecular structure of tight junctions and their role in epithelial transport. News Physiol. Sci.,  2001, 16, 126-130.
[http://dx.doi.org/10.1152/physiologyonline.2001.16.3.126] [PMID: 11443232] 
[189] 
Lo, C.M.; Keese, C.R.; Giaever, I. Cell-substrate contact: another factor may influence transepithelial electrical resistance of cell layers cultured on permeable filters. Exp. Cell Res.,  1999, 250(2), 576-580.
[http://dx.doi.org/10.1006/excr.1999.4538] [PMID: 10413610] 
[190] 
Bergmann, S.; Lawler, S.E.; Qu, Y.; Fadzen, C.M.; Wolfe, J.M.; Regan, M.S.; Pentelute, B.L.; Agar, N.Y.R.; Cho, C-F. Blood-brain-barrier organoids for investigating the permeability of CNS therapeutics. Nat. Protoc.,  2018, 13(12), 2827-2843.
[http://dx.doi.org/10.1038/s41596-018-0066-x] [PMID: 30382243] 
[191] 
Nagaraja, T.N.; Keenan, K.A.; Fenstermacher, J.D.; Knight, R.A. Acute leakage patterns of fluorescent plasma flow markers after transient focal cerebral ischemia suggest large openings in blood-brain barrier. Microcirculation,  2008, 15(1), 1-14.
[http://dx.doi.org/10.1080/10739680701409811] [PMID: 17934962] 
[192] 
Kassner, A.; Merali, Z. Assessment of Blood-Brain Barrier Disruption in Stroke. Stroke,  2015, 46(11), 3310-3315.
[http://dx.doi.org/10.1161/STROKEAHA.115.008861] [PMID: 26463696] 
[193] 
Jin, A.Y.; Tuor, U.I.; Rushforth, D.; Kaur, J.; Muller, R.N.; Petterson, J.L.; Boutry, S.; Barber, P.A. Reduced blood brain barrier breakdown in P-selectin deficient mice following transient ischemic stroke: a future therapeutic target for treatment of stroke. BMC Neurosci.,  2010, 11, 12.
[http://dx.doi.org/10.1186/1471-2202-11-12] [PMID: 20122276] 
[194] 
Sladojevic, N.; Stamatovic, S.M.; Keep, R.F.; Grailer, J.J.; Sarma, J.V.; Ward, P.A.; Andjelkovic, A.V. Inhibition of junctional adhesion molecule-A/LFA interaction attenuates leukocyte trafficking and inflammation in brain ischemia/reperfusion injury. Neurobiol. Dis.,  2014, 67, 57-70.
[http://dx.doi.org/10.1016/j.nbd.2014.03.010] [PMID: 24657919] 
[195] 
Tso, M.K.; Macdonald, R.L. Subarachnoid hemorrhage: a review of experimental studies on the microcirculation and the neurovascular unit. Transl. Stroke Res.,  2014, 5(2), 174-189.
[http://dx.doi.org/10.1007/s12975-014-0323-4] [PMID: 24510780] 
[196] 
Zhou, Y.; Wang, Y.; Wang, J.; Anne Stetler, R.; Yang, Q-W. Inflammation in intracerebral hemorrhage: from mechanisms to clinical translation. Prog. Neurobiol.,  2014, 115, 25-44.
[http://dx.doi.org/10.1016/j.pneurobio.2013.11.003] [PMID: 24291544] 
[197] 
Takeshita, Y.; Ransohoff, R.M. Inflammatory cell trafficking across the blood-brain barrier: chemokine regulation and in vitro models. Immunol. Rev.,  2012, 248(1), 228-239.
[http://dx.doi.org/10.1111/j.1600-065X.2012.01127.x] [PMID: 22725965] 
[198] 
Coisne, C.; Engelhardt, B. Tight junctions in brain barriers during central nervous system inflammation Antioxidants redox Signal,  2011, 15, 1285-1303.
[http://dx.doi.org/10.1089/ars.2011.3929] 
[199] 
Miah, M.K.; Chowdhury, E.A.; Bickel, U.; Mehvar, R. Evaluation of [14C] and [13C]Sucrose as Blood-Brain Barrier Permeability Markers. J. Pharm. Sci.,  2017, 106(6), 1659-1669.
[http://dx.doi.org/10.1016/j.xphs.2017.02.011] [PMID: 28238901] 
[200] 
Pfefferkorn, T.; Rosenberg, G.A. Closure of the blood-brain barrier by matrix metalloproteinase inhibition reduces rtPA-mediated mortality in cerebral ischemia with delayed reperfusion. Stroke,  2003, 34(8), 2025-2030.
[http://dx.doi.org/10.1161/01.STR.0000083051.93319.28] [PMID: 12855824] 
[201] 
Tibbling, G.; Link, H.; Ohman, S. Principles of albumin and IgG analyses in neurological disorders. I. Establishment of reference values. Scand. J. Clin. Lab. Invest.,  1977, 37(5), 385-390.
[http://dx.doi.org/10.3109/00365517709091496] [PMID: 337459] 
[202] 
Link, H.; Tibbling, G. Principles of albumin and IgG analyses in neurological disorders. II. Relation of the concentration of the proteins in serum and cerebrospinal fluid. Scand. J. Clin. Lab. Invest.,  1977, 37(5), 391-396.
[http://dx.doi.org/10.3109/00365517709091497] [PMID: 337460] 
[203] 
Reiber, H. Dynamics of brain-derived proteins in cerebrospinal fluid. Clin. Chim. Acta,  2001, 310(2), 173-186.
[http://dx.doi.org/10.1016/S0009-8981(01)00573-3] [PMID: 11498083] 
[204] 
Reiber, H. The discrimination between different blood-CSF barrier dysfunctions and inflammatory reactions of the CNS by a recent evaluation graph for the protein profile of cerebrospinal fluid. J. Neurol.,  1980, 224(2), 89-99.
[http://dx.doi.org/10.1007/BF00313347] [PMID: 6160221] 
[205] 
Blyth, B.J.; Farahvar, A.; He, H.; Nayak, A.; Yang, C.; Shaw, G.; Bazarian, J.J. Elevated serum ubiquitin carboxy-terminal hydrolase L1 is associated with abnormal blood-brain barrier function after traumatic brain injury. J. Neurotrauma,  2011, 28(12), 2453-2462.
[http://dx.doi.org/10.1089/neu.2010.1653] [PMID: 21428722] 
[206] 
Kazmierski, R.; Michalak, S.; Wencel-Warot, A.; Nowinski, W.L. Serum tight-junction proteins predict hemorrhagic transformation in ischemic stroke patients. Neurology,  2012, 79(16), 1677-1685.
[http://dx.doi.org/10.1212/WNL.0b013e31826e9a83] [PMID: 22993287] 
[207] 
Blyth, B.J.; Farhavar, A.; Gee, C.; Hawthorn, B.; He, H.; Nayak, A.; Stöcklein, V.; Bazarian, J.J. Validation of serum markers for blood-brain barrier disruption in traumatic brain injury. J. Neurotrauma,  2009, 26(9), 1497-1507.
[http://dx.doi.org/10.1089/neu.2008.0738] [PMID: 19257803] 
[208] 
Castellanos, M.; Sobrino, T.; Millán, M.; García, M.; Arenillas, J.; Nombela, F.; Brea, D.; Perez de la Ossa, N.; Serena, J.; Vivancos, J.; Castillo, J.; Dávalos, A. Serum cellular fibronectin and matrix metalloproteinase-9 as screening biomarkers for the prediction of parenchymal hematoma after thrombolytic therapy in acute ischemic stroke: a multicenter confirmatory study. Stroke,  2007, 38(6), 1855-1859.
[http://dx.doi.org/10.1161/STROKEAHA.106.481556] [PMID: 17478737] 
[209] 
Castellanos, M.; Leira, R.; Serena, J.; Blanco, M.; Pedraza, S.; Castillo, J.; Dávalos, A. Plasma cellular-fibronectin concentration predicts hemorrhagic transformation after thrombolytic therapy in acute ischemic stroke. Stroke,  2004, 35(7), 1671-1676.
[http://dx.doi.org/10.1161/01.STR.0000131656.47979.39] [PMID: 15166391] 
[210] 
Peeyush Kumar, T.; McBride, D.W.; Dash, P.K.; Matsumura, K.; Rubi, A.; Blackburn, S.L. Endothelial Cell Dysfunction and Injury in Subarachnoid Hemorrhage. Mol. Neurobiol.,  2019, 56(3), 1992-2006.
[http://dx.doi.org/10.1007/s12035-018-1213-7] [PMID: 29982982] 
[211] 
Guo, Z.; Sun, X.; He, Z.; Jiang, Y.; Zhang, X.; Zhang, J.H. Matrix metalloproteinase-9 potentiates early brain injury after subarachnoid hemorrhage. Neurol. Res.,  2010, 32(7), 715-720.
[http://dx.doi.org/10.1179/016164109X12478302362491] [PMID: 19703360] 
[212] 
Chou, S.H-Y.; Feske, S.K.; Simmons, S.L.; Konigsberg, R.G.J.; Orzell, S.C.; Marckmann, A.; Bourget, G.; Bauer, D.J.; De Jager, P.L.; Du, R.; Arai, K.; Lo, E.H.; Ning, M.M. Elevated peripheral neutrophils and matrix metalloproteinase 9 as biomarkers of functional outcome following subarachnoid hemorrhage. Transl. Stroke Res.,  2011, 2(4), 600-607.
[http://dx.doi.org/10.1007/s12975-011-0117-x] [PMID: 22207885] 
[213] 
Steliga, A.; Kowiański, P.; Czuba, E.; Waśkow, M.; Moryś, J.; Lietzau, G. Neurovascular Unit as a Source of Ischemic Stroke Biomarkers-Limitations of Experimental Studies and Perspectives for Clinical Application. Transl. Stroke Res.,  2019, 11(4), 553-579.
[http://dx.doi.org/10.1007/s12975-019-00744-5] [PMID: 31701356] 
[214] 
Ozkul-Wermester, O.; Guegan-Massardier, E.; Triquenot, A.; Borden, A.; Perot, G.; Gérardin, E. Increased blood-brain barrier permeability on perfusion computed tomography predicts hemorrhagic transformation in acute ischemic stroke. Eur. Neurol.,  2014, 72(1-2), 45-53.
[http://dx.doi.org/10.1159/000358297] [PMID: 24853726] 
[215] 
Hom, J.; Dankbaar, J.W.; Soares, B.P.; Schneider, T.; Cheng, S-C.; Bredno, J.; Lau, B.C.; Smith, W.; Dillon, W.P.; Wintermark, M. Blood-brain barrier permeability assessed by perfusion CT predicts symptomatic hemorrhagic transformation and malignant edema in acute ischemic stroke. AJNR Am. J. Neuroradiol.,  2011, 32(1), 41-48.
[http://dx.doi.org/10.3174/ajnr.A2244] [PMID: 20947643] 
[216] 
Lansberg, M.G.; Thijs, V.N.; Bammer, R.; Kemp, S.; Wijman, C.A.C.; Marks, M.P.; Albers, G.W. DEFUSE Investigators Risk factors of symptomatic intracerebral hemorrhage after tPA therapy for acute stroke. Stroke,  2007, 38(8), 2275-2278.
[http://dx.doi.org/10.1161/STROKEAHA.106.480475] [PMID: 17569874] 
[217] 
Rebeles, F.; Fink, J.; Anzai, Y.; Maravilla, K.R. Blood-brain barrier imaging and therapeutic potentials. Top. Magn. Reson. Imaging,  2006, 17(2), 107-116.
[http://dx.doi.org/10.1097/RMR.0b013e31802f5df9] [PMID: 17198226] 
[218] 
Nagaraja, T.N.; Knight, R.A.; Ewing, J.R.; Karki, K.; Nagesh, V.; Fenstermacher, J.D. Multiparametric magnetic resonance imaging and repeated measurements of blood-brain barrier permeability to contrast agents. Methods Mol. Biol.,  2011, 686, 193-212.
[http://dx.doi.org/10.1007/978-1-60761-938-3_8] [PMID: 21082372] 
[219] 
Heye, A.K.; Culling, R.D. Valdés Hernández, Mdel.C.; Thrippleton, M.J.; Wardlaw, J.M. Assessment of blood-brain barrier disruption using dynamic contrast-enhanced MRI. A systematic review. Neuroimage Clin.,  2014, 6, 262-274.
[http://dx.doi.org/10.1016/j.nicl.2014.09.002] [PMID: 25379439] 
[220] 
Sourbron, S.P.; Buckley, D.L. Tracer kinetic modelling in MRI: estimating perfusion and capillary permeability. Phys. Med. Biol.,  2012, 57(2), R1-R33.
[http://dx.doi.org/10.1088/0031-9155/57/2/R1] [PMID: 22173205] 
[221] 
Knight, R.A.; Nagaraja, T.N.; Ewing, J.R.; Nagesh, V.; Whitton, P.A.; Bershad, E.; Fagan, S.C.; Fenstermacher, J.D. Quantitation and localization of blood-to-brain influx by magnetic resonance imaging and quantitative autoradiography in a model of transient focal ischemia. Magn. Reson. Med.,  2005, 54(4), 813-821.
[http://dx.doi.org/10.1002/mrm.20629] [PMID: 16142715] 
[222] 
Schellenberg, A.E.; Buist, R.; Yong, V.W.; Del Bigio, M.R.; Peeling, J. Magnetic resonance imaging of blood-spinal cord barrier disruption in mice with experimental autoimmune encephalomyelitis. Magn. Reson. Med.,  2007, 58(2), 298-305.
[http://dx.doi.org/10.1002/mrm.21289] [PMID: 17654586] 
[223] 
Warach, S.; Latour, L.L. Evidence of reperfusion injury, exacerbated by thrombolytic therapy, in human focal brain ischemia using a novel imaging marker of early blood-brain barrier disruption. Stroke,  2004, 35(11)(Suppl. 1), 2659-2661.
[http://dx.doi.org/10.1161/01.STR.0000144051.32131.09] [PMID: 15472105] 
[224] 
Chassidim, Y.; Veksler, R.; Lublinsky, S.; Pell, G.S.; Friedman, A.; Shelef, I. Quantitative imaging assessment of blood-brain barrier permeability in humans. Fluids Barriers CNS,  2013, 10(1), 9.
[http://dx.doi.org/10.1186/2045-8118-10-9] [PMID: 23388348] 
[225] 
Roberts, C.; Issa, B.; Stone, A.; Jackson, A.; Waterton, J.C.; Parker, G.J.M. Comparative study into the robustness of compartmental modeling and model-free analysis in DCE-MRI studies. J. Magn. Reson. Imaging,  2006, 23(4), 554-563.
[http://dx.doi.org/10.1002/jmri.20529] [PMID: 16506143] 
[226] 
Alonzi, R.; Taylor, N.J.; Stirling, J.J.; d’Arcy, J.A.; Collins, D.J.; Saunders, M.I.; Hoskin, P.J.; Padhani, A.R. Reproducibility and correlation between quantitative and semiquantitative dynamic and intrinsic susceptibility-weighted MRI parameters in the benign and malignant human prostate. J. Magn. Reson. Imaging,  2010, 32(1), 155-164.
[http://dx.doi.org/10.1002/jmri.22215] [PMID: 20578023] 
[227] 
Jackson, A.; Jayson, G.C.; Li, K.L.; Zhu, X.P.; Checkley, D.R.; Tessier, J.J.L.; Waterton, J.C. Reproducibility of quantitative dynamic contrast-enhanced MRI in newly presenting glioma. Br. J. Radiol.,  2003, 76(903), 153-162.
[http://dx.doi.org/10.1259/bjr/70653746] [PMID: 12684231] 
[228] 
Thrippleton, M.J.; Backes, W.H.; Sourbron, S.; Ingrisch, M.; van Osch, M.J.P.; Dichgans, M.; Fazekas, F.; Ropele, S.; Frayne, R.; van Oostenbrugge, R.J.; Smith, E.E.; Wardlaw, J.M. Quantifying blood-brain barrier leakage in small vessel disease: Review and consensus recommendations. Alzheimers Dement.,  2019, 15(6), 840-858.
[http://dx.doi.org/10.1016/j.jalz.2019.01.013] [PMID: 31031101] 
[229] 
Lorberboym, M.; Lampl, Y.; Sadeh, M. Correlation of 99mTc-DTPA SPECT of the blood-brain barrier with neurologic outcome after acute stroke. J. Nucl. Med.,  2003, 44(12), 1898-1904.
[PMID: 14660714] 
[230] 
Gilad, R.; Lampl, Y.; Eilam, A.; Boaz, M.; Loyberboim, M. SPECT-DTPA as a tool for evaluating the blood-brain barrier in post-stroke seizures. J. Neurol.,  2012, 259(10), 2041-2044.
[http://dx.doi.org/10.1007/s00415-012-6445-2] [PMID: 22323212] 
[231] 
Olsen, T.S. Post-stroke epilepsy. Curr. Atheroscler. Rep.,  2001, 3(4), 340-344.
[http://dx.doi.org/10.1007/s11883-001-0029-4] [PMID: 11389801] 
[232] 
Barth, A.; Haldemann, A.R.; Reubi, J.C.; Godoy, N.; Rösler, H.; Kinser, J.A.; Seiler, R.W. Noninvasive differentiation of meningiomas from other brain tumours using combined 111Indium-octreotide/99mtechnetium-DTPA brain scintigraphy. Acta Neurochir. (Wien),  1996, 138(10), 1179-1185.
[http://dx.doi.org/10.1007/BF01809748] [PMID: 8955437] 
[233] 
Inoue, Y.; Momose, T.; Machida, K.; Honda, N.; Mamiya, T.; Takahashi, T.; Sasaki, Y. Delayed imaging of Tc-99m-DTPA-HSA SPECT in subacute cerebral infarction. Radiat. Med.,  1993, 11(5), 214-216.
[PMID: 8290699] 
[234] 
Shih, W.J.; Domstad, P.A.; DeLand, F.H. Opportunistic intracranial infection in AIDS detection by technetium-99m DTPA brain scintigraphy. J. Nucl. Med.,  1986, 27(4), 498-501.
[PMID: 3712064] 
[235] 
Keep, R.F.; Xiang, J.; Ennis, S.R.; Andjelkovic, A.; Hua, Y.; Xi, G.; Hoff, J.T. Blood-brain barrier function in intracerebral hemorrhage. Acta Neurochir. Suppl. (Wien),  2008, 105, 73-77.
[http://dx.doi.org/10.1007/978-3-211-09469-3_15] [PMID: 19066086] 
[236] 
Sun, Y.; Feng, X.; Ding, Y.; Li, M.; Yao, J.; Wang, L.; Gao, Z. Phased Treatment Strategies for Cerebral Ischemia Based on Glutamate Receptors. Front. Cell. Neurosci.,  2019, 13, 168.
[http://dx.doi.org/10.3389/fncel.2019.00168] [PMID: 31105534] 
[237] 
Jiang, X.; Andjelkovic, A.V.; Zhu, L.; Yang, T.; Bennett, M.V.L.; Chen, J.; Keep, R.F.; Shi, Y. Blood-brain barrier dysfunction and recovery after ischemic stroke. Prog. Neurobiol.,  2018, 163-164, 144-171.
[http://dx.doi.org/10.1016/j.pneurobio.2017.10.001] [PMID: 28987927] 
[238] 
Lipton, S.A.; Rosenberg, P.A. Excitatory amino acids as a final common pathway for neurologic disorders. N. Engl. J. Med.,  1994, 330(9), 613-622.
[http://dx.doi.org/10.1056/NEJM199403033300907] [PMID: 7905600] 
[239] 
Ankarcrona, M.; Dypbukt, J.M.; Bonfoco, E.; Zhivotovsky, B.; Orrenius, S.; Lipton, S.A.; Nicotera, P. Glutamate-induced neuronal death: a succession of necrosis or apoptosis depending on mitochondrial function. Neuron,  1995, 15(4), 961-973.
[http://dx.doi.org/10.1016/0896-6273(95)90186-8] [PMID: 7576644] 
[240] 
Geraghty, J.R.; Davis, J.L.; Testai, F.D. Neuroinflammation and Microvascular Dysfunction After Experimental Subarachnoid Hemorrhage: Emerging Components of Early Brain Injury Related to Outcome. Neurocrit. Care,  2019, 31(2), 373-389.
[http://dx.doi.org/10.1007/s12028-019-00710-x] [PMID: 31012056] 
[241] 
Tang, D.; Kang, R.; Coyne, C.B.; Zeh, H.J.; Lotze, M.T. PAMPs and DAMPs: signal 0s that spur autophagy and immunity. Immunol. Rev.,  2012, 249(1), 158-175.
[http://dx.doi.org/10.1111/j.1600-065X.2012.01146.x] [PMID: 22889221] 
[242] 
Sifat, A.E.; Vaidya, B.; Abbruscato, T.J. Blood-Brain Barrier Protection as a Therapeutic Strategy for Acute Ischemic Stroke. AAPS J.,  2017, 19(4), 957-972.
[http://dx.doi.org/10.1208/s12248-017-0091-7] [PMID: 28484963] 
[243] 
Lee, C.Z.; Xue, Z.; Zhu, Y.; Yang, G-Y.Y.G-Y.; Young, W.L. Matrix metalloproteinase-9 inhibition attenuates vascular endothelial growth factor-induced intracerebral hemorrhage. Stroke,  2007, 38(9), 2563-2568.
[http://dx.doi.org/10.1161/STROKEAHA.106.481515] [PMID: 17673717] 
[244] 
Suzuki, H.; Fujimoto, M.; Kawakita, F.; Liu, L.; Nakatsuka, Y.; Nakano, F.; Nishikawa, H.; Okada, T.; Kanamaru, H.; Imanaka-Yoshida, K.; Yoshida, T.; Shiba, M. Tenascin-C in brain injuries and edema after subarachnoid hemorrhage: Findings from basic and clinical studies. J. Neurosci. Res.,  2020, 98(1), 42-56.
[http://dx.doi.org/10.1002/jnr.24330] [PMID: 30242870] 
[245] 
Kanamaru, H.; Suzuki, H. Potential therapeutic molecular targets for blood-brain barrier disruption after subarachnoid hemorrhage. Neural Regen. Res.,  2019, 14(7), 1138-1143.
[http://dx.doi.org/10.4103/1673-5374.251190] [PMID: 30804237] 
[246] 
Friedrich, V.; Flores, R.; Sehba, F.A. Cell death starts early after subarachnoid hemorrhage. Neurosci. Lett.,  2012, 512(1), 6-11.
[http://dx.doi.org/10.1016/j.neulet.2012.01.036] [PMID: 22306092] 
[247] 
Suzuki, H. What is early brain injury? Transl. Stroke Res.,  2015, 6(1), 1-3.
[http://dx.doi.org/10.1007/s12975-014-0380-8] [PMID: 25502277] 
[248] 
Yang, G.Y.; Betz, A.L. Reperfusion-induced injury to the blood-brain barrier after middle cerebral artery occlusion in rats. Stroke,  1994, 25(8), 1658-1664.
[http://dx.doi.org/10.1161/01.STR.25.8.1658] [PMID: 8042219] 
[249] 
Li, Y.; Xu, L.; Zeng, K.; Xu, Z.; Suo, D.; Peng, L.; Ren, T.; Sun, Z.; Yang, W.; Jin, X.; Yang, L. Propane-2-sulfonic acid octadec-9-enyl-amide, a novel PPARα/γ dual agonist, protects against ischemia-induced brain damage in mice by inhibiting inflammatory responses. Brain Behav. Immun.,  2017, 66, 289-301.
[http://dx.doi.org/10.1016/j.bbi.2017.07.015] [PMID: 28736035] 
[250] 
Krafft, P.R.; Caner, B.; Klebe, D.; Rolland, W.B.; Tang, J.; Zhang, J.H. PHA-543613 preserves blood-brain barrier integrity after intracerebral hemorrhage in mice. Stroke,  2013, 44(6), 1743-1747.
[http://dx.doi.org/10.1161/STROKEAHA.111.000427] [PMID: 23613493] 
[251] 
Li, Z.; Chen, X.; Zhang, X.; Ren, X.; Chen, X.; Cao, J.; Zang, W.; Liu, X.; Guo, F. Small Interfering RNA Targeting Dickkopf-1 Contributes to Neuroprotection After Intracerebral Hemorrhage in Rats. J. Mol. Neurosci.,  2017, 61(2), 279-288.
[http://dx.doi.org/10.1007/s12031-017-0883-3] [PMID: 28097491] 
[252] 
Sun, H.; Tang, Y.; Guan, X.; Li, L.; Wang, D. Effects of selective hypothermia on blood-brain barrier integrity and tight junction protein expression levels after intracerebral hemorrhage in rats. Biol. Chem.,  2013, 394(10), 1317-1324.
[http://dx.doi.org/10.1515/hsz-2013-0142] [PMID: 23828426] 
[253] 
Wang, T.; Chen, X.; Wang, Z.; Zhang, M.; Meng, H.; Gao, Y.; Luo, B.; Tao, L.; Chen, Y. Poloxamer-188 can attenuate blood-brain barrier damage to exert neuroprotective effect in mice intracerebral hemorrhage model. J. Mol. Neurosci.,  2015, 55(1), 240-250.
[http://dx.doi.org/10.1007/s12031-014-0313-8] [PMID: 24770901] 
[254] 
Wanyong, Y.; Zefeng, T.; Xiufeng, X.; Dawei, D.; Xiaoyan, L.; Ying, Z.; Yaogao, F. Tempol alleviates intracerebral hemorrhage-induced brain injury possibly by attenuating nitrative stress. Neuroreport,  2015, 26(14), 842-849.
[http://dx.doi.org/10.1097/WNR.0000000000000434] [PMID: 26237245] 
[255] 
Xie, R-X.; Li, D-W.; Liu, X-C.; Yang, M-F.; Fang, J.; Sun, B-L.; Zhang, Z-Y.; Yang, X-Y. Carnosine Attenuates Brain Oxidative Stress and Apoptosis After Intracerebral Hemorrhage in Rats. Neurochem. Res.,  2017, 42(2), 541-551.
[http://dx.doi.org/10.1007/s11064-016-2104-9] [PMID: 27868153] 
[256] 
Yang, Y.; Zhang, Y.; Wang, Z.; Wang, S.; Gao, M.; Xu, R.; Liang, C.; Zhang, H. Attenuation of Acute Phase Injury in Rat Intracranial Hemorrhage by Cerebrolysin that Inhibits Brain Edema and Inflammatory Response. Neurochem. Res.,  2016, 41(4), 748-757.
[http://dx.doi.org/10.1007/s11064-015-1745-4] [PMID: 26498936] 
[257] 
Sun, Y.; Dai, M.; Wang, Y.; Wang, W.; Sun, Q.; Yang, G-Y.; Bian, L. Neuroprotection and sensorimotor functional improvement by curcumin after intracerebral hemorrhage in mice. J. Neurotrauma,  2011, 28(12), 2513-2521.
[http://dx.doi.org/10.1089/neu.2011.1958] [PMID: 21770745] 
[258] 
Nadeau, C.A.; Dietrich, K.; Wilkinson, C.M.; Crawford, A.M.; George, G.N.; Nichol, H.K.; Colbourne, F. Prolonged Blood-Brain Barrier Injury Occurs After Experimental Intracerebral Hemorrhage and Is Not Acutely Associated with Additional Bleeding. Transl. Stroke Res.,  2019, 10(3), 287-297.
[http://dx.doi.org/10.1007/s12975-018-0636-9] [PMID: 29949086] 
[259] 
Keep, R.F.; Hua, Y.; Xi, G. Intracerebral haemorrhage: mechanisms of injury and therapeutic targets. Lancet Neurol.,  2012, 11(8), 720-731.
[http://dx.doi.org/10.1016/S1474-4422(12)70104-7] [PMID: 22698888] 
[260] 
Fumoto, T.; Naraoka, M.; Katagai, T.; Li, Y.; Shimamura, N.; Ohkuma, H. The Role of Oxidative Stress in Microvascular Disturbances after Experimental Subarachnoid Hemorrhage. Transl. Stroke Res.,  2019, 10(6), 684-694.
[http://dx.doi.org/10.1007/s12975-018-0685-0] [PMID: 30628008] 
[261] 
Li, Z.; Liang, G.; Ma, T.; Li, J.; Wang, P.; Liu, L.; Yu, B.; Liu, Y.; Xue, Y. Blood-brain barrier permeability change and regulation mechanism after subarachnoid hemorrhage. Metab. Brain Dis.,  2015, 30(2), 597-603.
[http://dx.doi.org/10.1007/s11011-014-9609-1] [PMID: 25270004] 
[262] 
Suzuki, H. Inflammation: a Good Research Target to Improve Outcomes of Poor-Grade Subarachnoid Hemorrhage. Transl. Stroke Res.,  2019, 10(6), 597-600.
[http://dx.doi.org/10.1007/s12975-019-00713-y] [PMID: 31214920] 
[263] 
Xi, G.; Keep, R.F.; Hoff, J.T. Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol.,  2006, 5(1), 53-63.
[http://dx.doi.org/10.1016/S1474-4422(05)70283-0] [PMID: 16361023] 
[264] 
Aronowski, J.; Zhao, X. Molecular pathophysiology of cerebral hemorrhage: secondary brain injury. Stroke,  2011, 42(6), 1781-1786.
[http://dx.doi.org/10.1161/STROKEAHA.110.596718] [PMID: 21527759] 
[265] 
Taylor, R.A.; Sansing, L.H. Microglial responses after ischemic stroke and intracerebral hemorrhage. Clin. Dev. Immunol.,  2013, 2013746068
[http://dx.doi.org/10.1155/2013/746068] [PMID: 24223607] 
[266] 
Wang, J.; Doré, S. Inflammation after intracerebral hemorrhage. J. Cereb. Blood Flow Metab.,  2007, 27(5), 894-908.
[http://dx.doi.org/10.1038/sj.jcbfm.9600403] [PMID: 17033693] 
[267] 
Venkatesan, C.; Chrzaszcz, M.; Choi, N.; Wainwright, M.S. Chronic upregulation of activated microglia immunoreactive for galectin-3/Mac-2 and nerve growth factor following diffuse axonal injury. J. Neuroinflammation,  2010, 7, 32.
[http://dx.doi.org/10.1186/1742-2094-7-32] [PMID: 20507613] 
[268] 
Loane, D.J.; Byrnes, K.R. Role of microglia in neurotrauma. Neurotherapeutics,  2010, 7(4), 366-377.
[http://dx.doi.org/10.1016/j.nurt.2010.07.002] [PMID: 20880501] 
[269] 
Wan, S.; Cheng, Y.; Jin, H.; Guo, D.; Hua, Y.; Keep, R.F.; Xi, G. Microglia Activation and Polarization After Intracerebral Hemorrhage in Mice: the Role of Protease-Activated Receptor-1. Transl. Stroke Res.,  2016, 7(6), 478-487.
[http://dx.doi.org/10.1007/s12975-016-0472-8] [PMID: 27206851] 
[270] 
Zhao, H.; Garton, T.; Keep, R.F.; Hua, Y.; Xi, G. Microglia/Macrophage Polarization After Experimental Intracerebral Hemorrhage. Transl. Stroke Res.,  2015, 6(6), 407-409.
[http://dx.doi.org/10.1007/s12975-015-0428-4] [PMID: 26446073] 
[271] 
Zheng, Z.V.; Lyu, H.; Lam, S.Y.E.; Lam, P.K.; Poon, W.S.; Wong, G.K.C. The dynamics of microglial polarization reveal the resident neuroinflammatory responses after subarachnoid hemorrhage. Transl. Stroke Res.,  2019, 11(3), 433-449.
[PMID: 31628642] 
[272] 
Xue, M.; Del Bigio, M.R. Intracerebral injection of autologous whole blood in rats: time course of inflammation and cell death. Neurosci. Lett.,  2000, 283(3), 230-232.
[http://dx.doi.org/10.1016/S0304-3940(00)00971-X] [PMID: 10754230] 
[273] 
Schaefer, L. Complexity of danger: the diverse nature of damage-associated molecular patterns. J. Biol. Chem.,  2014, 289(51), 35237-35245.
[http://dx.doi.org/10.1074/jbc.R114.619304] [PMID: 25391648] 
[274] 
Chaudhry, S.R.; Hafez, A.; Rezai Jahromi, B.; Kinfe, T.M.; Lamprecht, A.; Niemelä, M.; Muhammad, S. Role of damage associated molecular pattern molecules (DAMPs) in aneurysmal subarachnoid hemorrhage (aSAH). Int. J. Mol. Sci.,  2018, 19(7), 19.
[http://dx.doi.org/10.3390/ijms19072035] [PMID: 30011792] 
[275] 
Okada, T.; Suzuki, H. Toll-like receptor 4 as a possible therapeutic target for delayed brain injuries after aneurysmal subarachnoid hemorrhage. Neural Regen. Res.,  2017, 12(2), 193-196.
[http://dx.doi.org/10.4103/1673-5374.200795] [PMID: 28400792] 
[276] 
Chen, G.; Zhang, S.; Shi, J.; Ai, J.; Hang, C. Effects of recombinant human erythropoietin (rhEPO) on JAK2/STAT3 pathway and endothelial apoptosis in the rabbit basilar artery after subarachnoid hemorrhage. Cytokine,  2009, 45(3), 162-168.
[http://dx.doi.org/10.1016/j.cyto.2008.11.015] [PMID: 19144539] 
[277] 
Zille, M.; Ikhsan, M.; Jiang, Y.; Lampe, J.; Wenzel, J.; Schwaninger, M. The impact of endothelial cell death in the brain and its role after stroke: A systematic review. Cell Stress,  2019, 3(11), 330-347.
[http://dx.doi.org/10.15698/cst2019.11.203] [PMID: 31799500] 
[278] 
Greenwood, J.; Heasman, S.J.; Alvarez, J.I.; Prat, A.; Lyck, R.; Engelhardt, B. Review: leucocyte-endothelial cell crosstalk at the blood-brain barrier: a prerequisite for successful immune cell entry to the brain. Neuropathol. Appl. Neurobiol.,  2011, 37(1), 24-39.
[http://dx.doi.org/10.1111/j.1365-2990.2010.01140.x] [PMID: 20946472] 
[279] 
Engelhardt, B. Immune cell entry into the central nervous system: involvement of adhesion molecules and chemokines. J. Neurol. Sci.,  2008, 274(1-2), 23-26.
[http://dx.doi.org/10.1016/j.jns.2008.05.019] [PMID: 18573502] 
[280] 
Moxon-Emre, I.; Schlichter, L.C. Neutrophil depletion reduces blood-brain barrier breakdown, axon injury, and inflammation after intracerebral hemorrhage. J. Neuropathol. Exp. Neurol.,  2011, 70(3), 218-235.
[http://dx.doi.org/10.1097/NEN.0b013e31820d94a5] [PMID: 21293296] 
[281] 
Wasserman, J.K.; Schlichter, L.C. Minocycline protects the blood-brain barrier and reduces edema following intracerebral hemorrhage in the rat. Exp. Neurol.,  2007, 207(2), 227-237.
[http://dx.doi.org/10.1016/j.expneurol.2007.06.025] [PMID: 17698063] 
[282] 
Okada, T.; Kawakita, F.; Nishikawa, H.; Nakano, F.; Liu, L.; Suzuki, H. Selective Toll-Like Receptor 4 Antagonists Prevent Acute Blood-Brain Barrier Disruption After Subarachnoid Hemorrhage in Mice. Mol. Neurobiol.,  2019, 56(2), 976-985.
[http://dx.doi.org/10.1007/s12035-018-1145-2] [PMID: 29855971] 
[283] 
Wang, L.; Zhang, X.; Liu, L.; Cui, L.; Yang, R.; Li, M.; Du, W. Tanshinone II A down-regulates HMGB1, RAGE, TLR4, NF-kappaB expression, ameliorates BBB permeability and endothelial cell function, and protects rat brains against focal ischemia. Brain Res.,  2010, 1321, 143-151.
[http://dx.doi.org/10.1016/j.brainres.2009.12.046] [PMID: 20043889] 
[284] 
Chen, G.; Shaw, M.H.; Kim, Y-G.; Nuñez, G. NOD-like receptors: role in innate immunity and inflammatory disease. Annu. Rev. Pathol.,  2009, 4, 365-398.
[http://dx.doi.org/10.1146/annurev.pathol.4.110807.092239] [PMID: 18928408] 
[285] 
Schroder, K.; Tschopp, J. The inflammasomes. Cell,  2010, 140(6), 821-832.
[http://dx.doi.org/10.1016/j.cell.2010.01.040] [PMID: 20303873] 
[286] 
Abderrazak, A.; Syrovets, T.; Couchie, D.; El Hadri, K.; Friguet, B.; Simmet, T.; Rouis, M. NLRP3 inflammasome: from a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases. Redox Biol.,  2015, 4, 296-307.
[http://dx.doi.org/10.1016/j.redox.2015.01.008] [PMID: 25625584] 
[287] 
Okada, T.; Suzuki, H. Mechanisms of neuroinflammation and inflammatory mediators involved in brain injury following subarachnoid hemorrhage. Histol. Histopathol.,  2020, 18208.
[PMID: 32026458] 
[288] 
Di Virgilio, F.; Dal Ben, D.; Sarti, A.C.; Giuliani, A.L.; Falzoni, S. The P2X7 Receptor in Infection and Inflammation. Immunity,  2017, 47(1), 15-31.
[http://dx.doi.org/10.1016/j.immuni.2017.06.020] [PMID: 28723547] 
[289] 
Monif, M.; Reid, C.A.; Powell, K.L.; Smart, M.L.; Williams, D.A. The P2X7 receptor drives microglial activation and proliferation: a trophic role for P2X7R pore. J. Neurosci.,  2009, 29(12), 3781-3791.
[http://dx.doi.org/10.1523/JNEUROSCI.5512-08.2009] [PMID: 19321774] 
[290] 
Tang, Y.; Illes, P. Regulation of adult neural progenitor cell functions by purinergic signaling. Glia,  2017, 65(2), 213-230.
[http://dx.doi.org/10.1002/glia.23056] [PMID: 27629990] 
[291] 
Mariathasan, S.; Weiss, D.S.; Newton, K.; McBride, J.; O’Rourke, K.; Roose-Girma, M.; Lee, W.P.; Weinrauch, Y.; Monack, D.M.; Dixit, V.M. Cryopyrin activates the inflammasome in response to toxins and ATP. Nature,  2006, 440(7081), 228-232.
[http://dx.doi.org/10.1038/nature04515] [PMID: 16407890] 
[292] 
Yamasaki, K.; Muto, J.; Taylor, K.R.; Cogen, A.L.; Audish, D.; Bertin, J.; Grant, E.P.; Coyle, A.J.; Misaghi, A.; Hoffman, H.M.; Gallo, R.L. NLRP3/cryopyrin is necessary for interleukin-1beta (IL-1beta) release in response to hyaluronan, an endogenous trigger of inflammation in response to injury. J. Biol. Chem.,  2009, 284(19), 12762-12771.
[http://dx.doi.org/10.1074/jbc.M806084200] [PMID: 19258328] 
[293] 
Chen, S.; Ma, Q.; Krafft, P.R.; Hu, Q.; Rolland, W., II; Sherchan, P.; Zhang, J.; Tang, J.; Zhang, J.H. P2X7R/cryopyrin inflammasome axis inhibition reduces neuroinflammation after SAH. Neurobiol. Dis.,  2013, 58, 296-307.
[http://dx.doi.org/10.1016/j.nbd.2013.06.011] [PMID: 23816751] 
[294] 
Khalafalla, M.G.; Woods, L.T.; Camden, J.M.; Khan, A.A.; Limesand, K.H.; Petris, M.J.; Erb, L.; Weisman, G.A. P2X7 receptor antagonism prevents IL-1β release from salivary epithelial cells and reduces inflammation in a mouse model of autoimmune exocrinopathy. J. Biol. Chem.,  2017, 292(40), 16626-16637.
[http://dx.doi.org/10.1074/jbc.M117.790741] [PMID: 28798231] 
[295] 
Lister, M.F.; Sharkey, J.; Sawatzky, D.A.; Hodgkiss, J.P.; Davidson, D.J.; Rossi, A.G.; Finlayson, K. The role of the purinergic P2X7 receptor in inflammation. J. Inflamm. (Lond.),  2007, 4, 5.
[http://dx.doi.org/10.1186/1476-9255-4-5] [PMID: 17367517] 
[296] 
Yang, Y.; Wang, H.; Kouadir, M.; Song, H.; Shi, F. Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors. Cell Death Dis.,  2019, 10(2), 128.
[http://dx.doi.org/10.1038/s41419-019-1413-8] [PMID: 30755589] 
[297] 
Chen, S.; Ma, Q.; Krafft, P.R.; Chen, Y.; Tang, J.; Zhang, J.; Zhang, J.H. P2X7 receptor antagonism inhibits p38 mitogen-activated protein kinase activation and ameliorates neuronal apoptosis after subarachnoid hemorrhage in rats. Crit. Care Med.,  2013, 41(12), e466-e474.
[http://dx.doi.org/10.1097/CCM.0b013e31829a8246] [PMID: 23963136] 
[298] 
Luo, Y.; Lu, J.; Ruan, W.; Guo, X.; Chen, S. MCC950 attenuated early brain injury by suppressing NLRP3 inflammasome after experimental SAH in rats. Brain Res. Bull.,  2019, 146, 320-326.
[http://dx.doi.org/10.1016/j.brainresbull.2019.01.027] [PMID: 30716395] 
[299] 
Cao, G.; Jiang, N.; Hu, Y.; Zhang, Y.; Wang, G.; Yin, M.; Ma, X.; Zhou, K.; Qi, J.; Yu, B.; Kou, J. Ruscogenin Attenuates Cerebral Ischemia-Induced Blood-Brain Barrier Dysfunction by Suppressing TXNIP/NLRP3 Inflammasome Activation and the MAPK Pathway. Int. J. Mol. Sci.,  2016, 17(9), 1418.
[http://dx.doi.org/10.3390/ijms17091418] [PMID: 27589720] 
[300] 
Ren, H.; Kong, Y.; Liu, Z.; Zang, D.; Yang, X.; Wood, K.; Li, M.; Liu, Q. Selective NLRP3 (Pyrin Domain-Containing Protein 3) Inflammasome Inhibitor Reduces Brain Injury After Intracerebral Hemorrhage. Stroke,  2018, 49(1), 184-192.
[http://dx.doi.org/10.1161/STROKEAHA.117.018904] [PMID: 29212744] 
[301] 
Bianchi, R.; Kastrisianaki, E.; Giambanco, I.; Donato, R. S100B protein stimulates microglia migration via RAGE-dependent up-regulation of chemokine expression and release. J. Biol. Chem.,  2011, 286(9), 7214-7226.
[http://dx.doi.org/10.1074/jbc.M110.169342] [PMID: 21209080] 
[302] 
Lee, E.J.; Park, J.H. Receptor for Advanced Glycation Endproducts (RAGE), Its Ligands, and Soluble RAGE: Potential Biomarkers for Diagnosis and Therapeutic Targets for Human Renal Diseases. Genomics Inform.,  2013, 11(4), 224-229.
[http://dx.doi.org/10.5808/GI.2013.11.4.224] [PMID: 24465234] 
[303] 
Rani, S.G.; Sepuru, K.M.; Yu, C. Interaction of S100A13 with C2 domain of receptor for advanced glycation end products (RAGE). Biochim. Biophys. Acta,  2014, 1844(9), 1718-1728.
[http://dx.doi.org/10.1016/j.bbapap.2014.06.017] [PMID: 24982031] 
[304] 
Rovere-Querini, P.; Capobianco, A.; Scaffidi, P.; Valentinis, B.; Catalanotti, F.; Giazzon, M.; Dumitriu, I.E.; Müller, S.; Iannacone, M.; Traversari, C.; Bianchi, M.E.; Manfredi, A.A. HMGB1 is an endogenous immune adjuvant released by necrotic cells. EMBO Rep.,  2004, 5(8), 825-830.
[http://dx.doi.org/10.1038/sj.embor.7400205] [PMID: 15272298] 
[305] 
Kim, S-W.; Lim, C-M.; Kim, J-B.; Shin, J-H.; Lee, S.; Lee, M.; Lee, J-K. Extracellular HMGB1 released by NMDA treatment confers neuronal apoptosis via RAGE-p38 MAPK/ERK signaling pathway. Neurotox. Res.,  2011, 20(2), 159-169.
[http://dx.doi.org/10.1007/s12640-010-9231-x] [PMID: 21116767] 
[306] 
Sparvero, L.J.; Asafu-Adjei, D.; Kang, R.; Tang, D.; Amin, N. Im, J.; Rutledge, R.; Lin, B.; Amoscato, A.A.; Zeh, H.J.; Lotze, M.T. RAGE (Receptor for Advanced Glycation Endproducts), RAGE ligands, and their role in cancer and inflammation. J. Transl. Med.,  2009, 7, 17.
[http://dx.doi.org/10.1186/1479-5876-7-17] [PMID: 19292913] 
[307] 
Wang, K-C.; Tang, S-C.; Lee, J-E.; Li, Y-I.; Huang, Y-S.; Yang, W-S.; Jeng, J-S.; Arumugam, T.V.; Tu, Y-K. Cerebrospinal fluid high mobility group box 1 is associated with neuronal death in subarachnoid hemorrhage. J. Cereb. Blood Flow Metab.,  2017, 37(2), 435-443.
[http://dx.doi.org/10.1177/0271678X16629484] [PMID: 26823474] 
[308] 
Taylor, R.A.; Chang, C-F.; Goods, B.A.; Hammond, M.D.; Mac Grory, B.; Ai, Y.; Steinschneider, A.F.; Renfroe, S.C.; Askenase, M.H.; McCullough, L.D.; Kasner, S.E.; Mullen, M.T.; Hafler, D.A.; Love, J.C.; Sansing, L.H. TGF-β1 modulates microglial phenotype and promotes recovery after intracerebral hemorrhage. J. Clin. Invest.,  2017, 127(1), 280-292.
[http://dx.doi.org/10.1172/JCI88647] [PMID: 27893460] 
[309] 
Hua, Y.; Wu, J.; Keep, R.F.; Nakamura, T.; Hoff, J.T.; Xi, G. Tumor necrosis factor-alpha increases in the brain after intracerebral hemorrhage and thrombin stimulation. Neurosurgery,  2006, 58(3), 542-550.
[http://dx.doi.org/10.1227/01.NEU.0000197333.55473.AD] [PMID: 16528196] 
[310] 
Shen, Y.; Gu, J.; Liu, Z.; Xu, C.; Qian, S.; Zhang, X.; Zhou, B.; Guan, Q.; Sun, Y.; Wang, Y.; Jin, X. Inhibition of HIF-1α Reduced Blood Brain Barrier Damage by Regulating MMP-2 and VEGF During Acute Cerebral Ischemia. Front. Cell. Neurosci.,  2018, 12, 288.
[http://dx.doi.org/10.3389/fncel.2018.00288] [PMID: 30233326] 
[311] 
Yang, Y.; Rosenberg, G.A. Blood-brain barrier breakdown in acute and chronic cerebrovascular disease. Stroke,  2011, 42(11), 3323-3328.
[http://dx.doi.org/10.1161/STROKEAHA.110.608257] [PMID: 21940972] 
[312] 
Könnecke, H.; Bechmann, I. The role of microglia and matrix metalloproteinases involvement in neuroinflammation and gliomas. Clin. Dev. Immunol.,  2013, 2013914104
[http://dx.doi.org/10.1155/2013/914104] [PMID: 24023566] 
[313] 
Zhao, L-R.; Navalitloha, Y.; Singhal, S.; Mehta, J.; Piao, C-S.; Guo, W-P.; Kessler, J.A.; Groothuis, D.R. Hematopoietic growth factors pass through the blood-brain barrier in intact rats. Exp. Neurol.,  2007, 204(2), 569-573.
[http://dx.doi.org/10.1016/j.expneurol.2006.12.001] [PMID: 17307165] 
[314] 
Xue, M.; Yong, V.W. Matrix metalloproteinases in intracerebral hemorrhage. Neurol. Res.,  2008, 30(8), 775-782.
[http://dx.doi.org/10.1179/174313208X341102] [PMID: 18826803] 
[315] 
Zhang, Z.; Yan, J.; Shi, H. Role of Hypoxia Inducible Factor 1 in Hyperglycemia-Exacerbated Blood-Brain Barrier Disruption in Ischemic Stroke. Neurobiol. Dis.,  2016, 95, 82-92.
[http://dx.doi.org/10.1016/j.nbd.2016.07.012] [PMID: 27425889] 
[316] 
Chen, W.; Jadhav, V.; Tang, J.; Zhang, J.H. HIF-1alpha inhibition ameliorates neonatal brain injury in a rat pup hypoxic-ischemic model. Neurobiol. Dis.,  2008, 31(3), 433-441.
[http://dx.doi.org/10.1016/j.nbd.2008.05.020] [PMID: 18602008] 
[317] 
Yang, Y.; Estrada, E.Y.; Thompson, J.F.; Liu, W.; Rosenberg, G.A. Matrix metalloproteinase-mediated disruption of tight junction proteins in cerebral vessels is reversed by synthetic matrix metalloproteinase inhibitor in focal ischemia in rat. J. Cereb. Blood Flow Metab.,  2007, 27(4), 697-709.
[http://dx.doi.org/10.1038/sj.jcbfm.9600375] [PMID: 16850029] 
[318] 
Yang, Y.; Rosenberg, G.A. MMP-mediated disruption of claudin-5 in the blood-brain barrier of rat brain after cerebral ischemia. Methods Mol. Biol.,  2011, 762, 333-345.
[http://dx.doi.org/10.1007/978-1-61779-185-7_24] [PMID: 21717368] 
[319] 
Zhang, S.; An, Q.; Wang, T.; Gao, S.; Zhou, G. Autophagy- and MMP-2/9-mediated Reduction and Redistribution of ZO-1 Contribute to Hyperglycemia-increased Blood-Brain Barrier Permeability During Early Reperfusion in Stroke. Neuroscience,  2018, 377, 126-137.
[http://dx.doi.org/10.1016/j.neuroscience.2018.02.035] [PMID: 29524637] 
[320] 
Kumari, R.; Willing, L.B.; Patel, S.D.; Baskerville, K.A.; Simpson, I.A. Increased cerebral matrix metalloprotease-9 activity is associated with compromised recovery in the diabetic db/db mouse following a stroke. J. Neurochem.,  2011, 119(5), 1029-1040.
[http://dx.doi.org/10.1111/j.1471-4159.2011.07487.x] [PMID: 21923664] 
[321] 
Lakhan, S.E.; Kirchgessner, A.; Tepper, D.; Leonard, A. Matrix metalloproteinases and blood-brain barrier disruption in acute ischemic stroke. Front. Neurol.,  2013, 4, 32.
[http://dx.doi.org/10.3389/fneur.2013.00032] [PMID: 23565108] 
[322] 
Liu, J.; Jin, X.; Liu, K.J.; Liu, W. Matrix metalloproteinase-2-mediated occludin degradation and caveolin-1-mediated claudin-5 redistribution contribute to blood-brain barrier damage in early ischemic stroke stage. J. Neurosci.,  2012, 32(9), 3044-3057.
[http://dx.doi.org/10.1523/JNEUROSCI.6409-11.2012] [PMID: 22378877] 
[323] 
Lischper, M.; Beuck, S.; Thanabalasundaram, G.; Pieper, C.; Galla, H-J. Metalloproteinase mediated occludin cleavage in the cerebral microcapillary endothelium under pathological conditions. Brain Res.,  2010, 1326, 114-127.
[http://dx.doi.org/10.1016/j.brainres.2010.02.054] [PMID: 20197061] 
[324] 
Li, Y.; Zhong, W.; Jiang, Z.; Tang, X. New progress in the approaches for blood-brain barrier protection in acute ischemic stroke. Brain Res. Bull.,  2019, 144, 46-57.
[http://dx.doi.org/10.1016/j.brainresbull.2018.11.006] [PMID: 30448453] 
[325] 
Wang, J.; Tsirka, S.E. Neuroprotection by inhibition of matrix metalloproteinases in a mouse model of intracerebral haemorrhage. Brain,  2005, 128(Pt 7), 1622-1633.
[http://dx.doi.org/10.1093/brain/awh489] [PMID: 15800021] 
[326] 
Xue, M.; Hollenberg, M.D.; Demchuk, A.; Yong, V.W. Relative importance of proteinase-activated receptor-1 versus matrix metalloproteinases in intracerebral hemorrhage-mediated neurotoxicity in mice. Stroke,  2009, 40(6), 2199-2204.
[http://dx.doi.org/10.1161/STROKEAHA.108.540393] [PMID: 19359644] 
[327] 
Rosenberg, G.A.; Navratil, M. Metalloproteinase inhibition blocks edema in intracerebral hemorrhage in the rat. Neurology,  1997, 48(4), 921-926.
[http://dx.doi.org/10.1212/WNL.48.4.921] [PMID: 9109878] 
[328] 
Wells, J.E.A.; Biernaskie, J.; Szymanska, A.; Larsen, P.H.; Yong, V.W.; Corbett, D. Matrix metalloproteinase (MMP)-12 expression has a negative impact on sensorimotor function following intracerebral haemorrhage in mice. Eur. J. Neurosci.,  2005, 21(1), 187-196.
[http://dx.doi.org/10.1111/j.1460-9568.2004.03829.x] [PMID: 15654856] 
[329] 
Matsukawa, N.; Yasuhara, T.; Hara, K.; Xu, L.; Maki, M.; Yu, G.; Kaneko, Y.; Ojika, K.; Hess, D.C.; Borlongan, C.V. Therapeutic targets and limits of minocycline neuroprotection in experimental ischemic stroke. BMC Neurosci.,  2009, 10, 126.
[http://dx.doi.org/10.1186/1471-2202-10-126] [PMID: 19807907] 
[330] 
Zabad, R.K.; Metz, L.M.; Todoruk, T.R.; Zhang, Y.; Mitchell, J.R.; Yeung, M.; Patry, D.G.; Bell, R.B.; Yong, V.W. The clinical response to minocycline in multiple sclerosis is accompanied by beneficial immune changes: a pilot study. Mult. Scler.,  2007, 13(4), 517-526.
[http://dx.doi.org/10.1177/1352458506070319] [PMID: 17463074] 
[331] 
Grossetete, M.; Rosenberg, G.A. Matrix metalloproteinase inhibition facilitates cell death in intracerebral hemorrhage in mouse. J. Cereb. Blood Flow Metab.,  2008, 28(4), 752-763.
[http://dx.doi.org/10.1038/sj.jcbfm.9600572] [PMID: 17971790] 
[332] 
Florczak-Rzepka, M.; Grond-Ginsbach, C.; Montaner, J.; Steiner, T. Matrix metalloproteinases in human spontaneous intracerebral hemorrhage: an update. Cerebrovasc. Dis.,  2012, 34(4), 249-262.
[http://dx.doi.org/10.1159/000341686] [PMID: 23052179] 
[333] 
Brouns, R.; Wauters, A.; De Surgeloose, D.; Mariën, P.; De Deyn, P.P. Biochemical markers for blood-brain barrier dysfunction in acute ischemic stroke correlate with evolution and outcome. Eur. Neurol.,  2011, 65(1), 23-31.
[http://dx.doi.org/10.1159/000321965] [PMID: 21135557] 
[334] 
Amantea, D.; Nappi, G.; Bernardi, G.; Bagetta, G.; Corasaniti, M.T. Post-ischemic brain damage: pathophysiology and role of inflammatory mediators. FEBS J.,  2009, 276(1), 13-26.
[http://dx.doi.org/10.1111/j.1742-4658.2008.06766.x] [PMID: 19087196] 
[335] 
Lee, J.E.; Yoon, Y.J.; Moseley, M.E.; Yenari, M.A. Reduction in levels of matrix metalloproteinases and increased expression of tissue inhibitor of metalloproteinase-2 in response to mild hypothermia therapy in experimental stroke. J. Neurosurg.,  2005, 103(2), 289-297.
[http://dx.doi.org/10.3171/jns.2005.103.2.0289] [PMID: 16175859] 
[336] 
Park, K-P.; Rosell, A.; Foerch, C.; Xing, C.; Kim, W.J.; Lee, S.; Opdenakker, G.; Furie, K.L.; Lo, E.H. Plasma and brain matrix metalloproteinase-9 after acute focal cerebral ischemia in rats. Stroke,  2009, 40(8), 2836-2842.
[http://dx.doi.org/10.1161/STROKEAHA.109.554824] [PMID: 19556529] 
[337] 
Reuter, B.; Rodemer, C.; Grudzenski, S.; Meairs, S.; Bugert, P.; Hennerici, M.G.; Fatar, M. Effect of simvastatin on MMPs and TIMPs in human brain endothelial cells and experimental stroke. Transl. Stroke Res.,  2015, 6(2), 156-159.
[http://dx.doi.org/10.1007/s12975-014-0381-7] [PMID: 25476155] 
[338] 
Lu, A.; Suofu, Y.; Guan, F.; Broderick, J.P.; Wagner, K.R.; Clark, J.F. Matrix metalloproteinase-2 deletions protect against hemorrhagic transformation after 1 h of cerebral ischemia and 23 h of reperfusion. Neuroscience,  2013, 253, 361-367.
[http://dx.doi.org/10.1016/j.neuroscience.2013.08.068] [PMID: 24035828] 
[339] 
Suofu, Y.; Clark, J.F.; Broderick, J.P.; Kurosawa, Y.; Wagner, K.R.; Lu, A. Matrix metalloproteinase-2 or -9 deletions protect against hemorrhagic transformation during early stage of cerebral ischemia and reperfusion. Neuroscience,  2012, 212, 180-189.
[http://dx.doi.org/10.1016/j.neuroscience.2012.03.036] [PMID: 22521821] 
[340] 
Asahi, M.; Sumii, T.; Fini, M.E.; Itohara, S.; Lo, E.H. Matrix metalloproteinase 2 gene knockout has no effect on acute brain injury after focal ischemia. Neuroreport,  2001, 12(13), 3003-3007.
[http://dx.doi.org/10.1097/00001756-200109170-00050] [PMID: 11588620] 
[341] 
Clark, A.W.; Krekoski, C.A.; Bou, S.S.; Chapman, K.R.; Edwards, D.R. Increased gelatinase A (MMP-2) and gelatinase B (MMP-9) activities in human brain after focal ischemia. Neurosci. Lett.,  1997, 238(1-2), 53-56.
[http://dx.doi.org/10.1016/S0304-3940(97)00859-8] [PMID: 9464653] 
[342] 
Li, N.; Liu, Y.F.; Ma, L.; Worthmann, H.; Wang, Y.L.; Wang, Y.J.; Gao, Y.P.; Raab, P.; Dengler, R.; Weissenborn, K.; Zhao, X.Q. Association of molecular markers with perihematomal edema and clinical outcome in intracerebral hemorrhage. Stroke,  2013, 44(3), 658-663.
[http://dx.doi.org/10.1161/STROKEAHA.112.673590] [PMID: 23391772] 
[343] 
Shi, W.; Wang, Z.; Pu, J.; Wang, R.; Guo, Z.; Liu, C.; Sun, J.; Gao, L.; Zhou, R. Changes of blood-brain barrier permeability following intracerebral hemorrhage and the therapeutic effect of minocycline in rats. Acta Neurochir. Suppl. (Wien),  2011, 110(Pt 2), 61-67.
[http://dx.doi.org/10.1007/978-3-7091-0356-2_12] [PMID: 21125447] 
[344] 
Orihuela, R.; McPherson, C.A.; Harry, G.J. Microglial M1/M2 polarization and metabolic states. Br. J. Pharmacol.,  2016, 173(4), 649-665.
[http://dx.doi.org/10.1111/bph.13139] [PMID: 25800044] 
[345] 
Lobo-Silva, D.; Carriche, G.M.; Castro, A.G.; Roque, S.; Saraiva, M. Balancing the immune response in the brain: IL-10 and its regulation. J. Neuroinflammation,  2016, 13(1), 297.
[http://dx.doi.org/10.1186/s12974-016-0763-8] [PMID: 27881137] 
[346] 
Holtman, I.R.; Skola, D.; Glass, C.K. Transcriptional control of microglia phenotypes in health and disease. J. Clin. Invest.,  2017, 127(9), 3220-3229.
[http://dx.doi.org/10.1172/JCI90604] [PMID: 28758903] 
[347] 
Jiang, C.T.; Wu, W.F.; Deng, Y.H.; Ge, J.W. Modulators of microglia activation and polarization in ischemic stroke.  (Review) Mol. Med. Rep.,  2020, 21(5), 2006-2018 . [Review].
[http://dx.doi.org/10.3892/mmr.2020.11003] [PMID: 32323760] 
[348] 
Fumagalli, S.; Fiordaliso, F.; Perego, C.; Corbelli, A.; Mariani, A.; De Paola, M.; De Simoni, M-G. The phagocytic state of brain myeloid cells after ischemia revealed by superresolution structured illumination microscopy. J. Neuroinflammation,  2019, 16(1), 9.
[http://dx.doi.org/10.1186/s12974-019-1401-z] [PMID: 30651101] 
[349] 
Kanazawa, M.; Ninomiya, I.; Hatakeyama, M.; Takahashi, T.; Shimohata, T. Microglia and Monocytes/Macrophages Polarization Reveal Novel Therapeutic Mechanism against Stroke. Int. J. Mol. Sci.,  2017, 18(10), 2135.
[http://dx.doi.org/10.3390/ijms18102135] [PMID: 29027964] 
[350] 
Zhao, S.C.; Ma, L.S.; Chu, Z.H.; Xu, H.; Wu, W.Q.; Liu, F. Regulation of microglial activation in stroke. Acta Pharmacol. Sin.,  2017, 38(4), 445-458.
[http://dx.doi.org/10.1038/aps.2016.162] [PMID: 28260801] 
[351] 
Zhao, X.; Zhang, Y.; Strong, R.; Grotta, J.C.; Aronowski, J. 15d-Prostaglandin J2 activates peroxisome proliferator-activated receptor-γ, promotes expression of catalase, and reduces inflammation, behavioral dysfunction, and neuronal loss after intracerebral hemorrhage in rats. J. Cereb. Blood Flow Metab.,  2006, 26(6), 811-820.
[http://dx.doi.org/10.1038/sj.jcbfm.9600233] [PMID: 16208315] 
[352] 
Zhao, X.; Grotta, J.; Gonzales, N.; Aronowski, J. Hematoma resolution as a therapeutic target: the role of microglia/macrophages. Stroke,  2009, 40(3)(Suppl.), S92-S94.
[http://dx.doi.org/10.1161/STROKEAHA.108.533158] [PMID: 19064796] 
[353] 
Neher, M.D.; Weckbach, S.; Huber-Lang, M.S.; Stahel, P.F. New insights into the role of peroxisome proliferator-activated receptors in regulating the inflammatory response after tissue injury. PPAR Res.,  2012, 2012728461
[http://dx.doi.org/10.1155/2012/728461]] [PMID: 22481914] 
[354] 
Al Ahmad, A.; Gassmann, M.; Ogunshola, O.O. Maintaining blood-brain barrier integrity: pericytes perform better than astrocytes during prolonged oxygen deprivation. J. Cell. Physiol.,  2009, 218(3), 612-622.
[http://dx.doi.org/10.1002/jcp.21638] [PMID: 19016245] 
[355] 
Hayashi, K.; Nakao, S.; Nakaoke, R.; Nakagawa, S.; Kitagawa, N.; Niwa, M. Effects of hypoxia on endothelial/pericytic co-culture model of the blood-brain barrier. Regul. Pept.,  2004, 123(1-3), 77-83.
[http://dx.doi.org/10.1016/j.regpep.2004.05.023] [PMID: 15518896] 
[356] 
Yemisci, M.; Gursoy-Ozdemir, Y.; Vural, A.; Can, A.; Topalkara, K.; Dalkara, T. Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery. Nat. Med.,  2009, 15(9), 1031-1037.
[http://dx.doi.org/10.1038/nm.2022] [PMID: 19718040] 
[357] 
Nishioku, T.; Dohgu, S.; Takata, F.; Eto, T.; Ishikawa, N.; Kodama, K.B.; Nakagawa, S.; Yamauchi, A.; Kataoka, Y. Detachment of brain pericytes from the basal lamina is involved in disruption of the blood-brain barrier caused by lipopolysaccharide-induced sepsis in mice. Cell. Mol. Neurobiol.,  2009, 29(3), 309-316.
[http://dx.doi.org/10.1007/s10571-008-9322-x] [PMID: 18987969] 
[358] 
Jung, K-H.; Chu, K.; Lee, S-T.; Bahn, J-J.; Jeon, D.; Kim, J-H.; Kim, S.; Won, C-H.; Kim, M.; Lee, S.K.; Roh, J-K. Multipotent PDGFRβ-expressing cells in the circulation of stroke patients. Neurobiol. Dis.,  2011, 41(2), 489-497.
[http://dx.doi.org/10.1016/j.nbd.2010.10.020] [PMID: 21074616] 
[359] 
Hall, C.N.; Reynell, C.; Gesslein, B.; Hamilton, N.B.; Mishra, A.; Sutherland, B.A.; O’Farrell, F.M.; Buchan, A.M.; Lauritzen, M.; Attwell, D.; O’Farrell, F.M.; Buchan, A.M.; Lauritzen, M.; Attwell, D. Capillary pericytes regulate cerebral blood flow in health and disease. Nature,  2014, 508(7494), 55-60.
[http://dx.doi.org/10.1038/nature13165] [PMID: 24670647] 
[360] 
Nahirney, P.C.; Reeson, P.; Brown, C.E. Ultrastructural analysis of blood-brain barrier breakdown in the peri-infarct zone in young adult and aged mice. J. Cereb. Blood Flow Metab.,  2016, 36(2), 413-425.
[http://dx.doi.org/10.1177/0271678X15608396] [PMID: 26661190] 
[361] 
Renner, O.; Tsimpas, A.; Kostin, S.; Valable, S.; Petit, E.; Schaper, W.; Marti, H.H. Time- and cell type-specific induction of platelet-derived growth factor receptor-β during cerebral ischemia. Brain Res. Mol. Brain Res.,  2003, 113(1-2), 44-51.
[http://dx.doi.org/10.1016/S0169-328X(03)00085-8] [PMID: 12750005] 
[362] 
Begum, G.; Song, S.; Wang, S.; Zhao, H.; Bhuiyan, M.I.H.; Li, E.; Nepomuceno, R.; Ye, Q.; Sun, M.; Calderon, M.J.; Stolz, D.B.; St Croix, C.; Watkins, S.C.; Chen, Y.; He, P.; Shull, G.E.; Sun, D. Selective knockout of astrocytic Na+/H+ exchanger isoform 1 reduces astrogliosis, BBB damage, infarction, and improves neurological function after ischemic stroke. Glia,  2018, 66(1), 126-144.
[http://dx.doi.org/10.1002/glia.23232] [PMID: 28925083] 
[363] 
Chiu, C-D.; Yao, N-W.; Guo, J-H.; Shen, C-C.; Lee, H-T.; Chiu, Y-P.; Ji, H-R.; Chen, X.; Chen, C-C.; Chang, C. Inhibition of astrocytic activity alleviates sequela in acute stages of intracerebral hemorrhage. Oncotarget,  2017, 8(55), 94850-94861.
[http://dx.doi.org/10.18632/oncotarget.22022] [PMID: 29212271] 
[364] 
Michinaga, S.; Koyama, Y. Dual Roles of Astrocyte-Derived Factors in Regulation of Blood-Brain Barrier Function after Brain Damage. Int. J. Mol. Sci.,  2019, 20(3), 571.
[http://dx.doi.org/10.3390/ijms20030571] [PMID: 30699952] 
[365] 
Golledge, J.; Clancy, P.; Maguire, J.; Lincz, L.; Koblar, S.; McEvoy, M.; Attia, J.; Levi, C.; Sturm, J.; Almeida, O.P.; Yeap, B.B.; Flicker, L.; Norman, P.E.; Hankey, G.J. Plasma angiopoietin-1 is lower after ischemic stroke and associated with major disability but not stroke incidence. Stroke,  2014, 45(4), 1064-1068.
[http://dx.doi.org/10.1161/STROKEAHA.113.004339] [PMID: 24569814] 
[366] 
Kawakita, F.; Kanamaru, H.; Asada, R.; Suzuki, H. Potential roles of matricellular proteins in stroke. Exp. Neurol.,  2019, 322113057
[http://dx.doi.org/10.1016/j.expneurol.2019.113057]] [PMID: 31499062] 
[367] 
Murphy-Ullrich, J.E.; Sage, E.H. Revisiting the matricellular concept. Matrix Biol.,  2014, 37, 1-14.
[http://dx.doi.org/10.1016/j.matbio.2014.07.005] [PMID: 25064829] 
[368] 
Fujimoto, M.; Shiba, M.; Kawakita, F.; Liu, L.; Shimojo, N.; Imanaka-Yoshida, K.; Yoshida, T.; Suzuki, H. Deficiency of tenascin-C and attenuation of blood-brain barrier disruption following experimental subarachnoid hemorrhage in mice. J. Neurosurg.,  2016, 124(6), 1693-1702.
[http://dx.doi.org/10.3171/2015.4.JNS15484] [PMID: 26473781] 
[369] 
Liu, L.; Kawakita, F.; Fujimoto, M.; Nakano, F.; Imanaka-Yoshida, K.; Yoshida, T.; Suzuki, H. Role of Periostin in Early Brain Injury After Subarachnoid Hemorrhage in Mice. Stroke,  2017, 48(4), 1108-1111.
[http://dx.doi.org/10.1161/STROKEAHA.117.016629] [PMID: 28242775] 
[370] 
Nishikawa, H.; Suzuki, H. Implications of periostin in the development of subarachnoid hemorrhage-induced brain injuries. Neural Regen. Res.,  2017, 12(12), 1982-1984.
[http://dx.doi.org/10.4103/1673-5374.221150] [PMID: 29323034] 
[371] 
Shiba, M.; Suzuki, H. Lessons from tenascin-C knockout mice and potential clinical application to subarachnoid hemorrhage. Neural Regen. Res.,  2019, 14(2), 262-264.
[http://dx.doi.org/10.4103/1673-5374.244789] [PMID: 30531008] 
[372] 
Nishikawa, H.; Suzuki, H. Possible Role of Inflammation and Galectin-3 in Brain Injury after Subarachnoid Hemorrhage. Brain Sci.,  2018, 8(2), 8.
[PMID: 29414883] 
[373] 
Nishikawa, H.; Liu, L.; Nakano, F.; Kawakita, F.; Kanamaru, H.; Nakatsuka, Y.; Okada, T.; Suzuki, H. Modified citrus pectin prevents blood-brain barrier disruption in mouse Subarachnoid hemorrhage by inhibiting Galectin-3. Stroke,  2018, 49(11), 2743-2751.
[http://dx.doi.org/10.1161/STROKEAHA.118.021757] [PMID: 30355205] 
[374] 
Kawakita, F.; Suzuki, H. Periostin in cerebrovascular disease. Neural Regen. Res.,  2020, 15(1), 63-64.
[http://dx.doi.org/10.4103/1673-5374.264456] [PMID: 31535648] 
[375] 
Suzuki, H.; Ayer, R.; Sugawara, T.; Chen, W.; Sozen, T.; Hasegawa, Y.; Kanamaru, K.; Zhang, J.H. Protective effects of recombinant osteopontin on early brain injury after subarachnoid hemorrhage in rats. Crit. Care Med.,  2010, 38(2), 612-618.
[http://dx.doi.org/10.1097/CCM.0b013e3181c027ae] [PMID: 19851092] 
[376] 
Zhang, W.; Zhu, L.; An, C.; Wang, R.; Yang, L.; Yu, W.; Li, P.; Gao, Y. The blood brain barrier in cerebral ischemic injury – Disruption and repair. Brain Hemorrhages,  2020, 1, 34-53.
[http://dx.doi.org/10.1016/j.hest.2019.12.004] 
[377] 
Gliem, M.; Krammes, K.; Liaw, L.; van Rooijen, N.; Hartung, H-P.; Jander, S. Macrophage-derived osteopontin induces reactive astrocyte polarization and promotes re-establishment of the blood brain barrier after ischemic stroke. Glia,  2015, 63(12), 2198-2207.
[http://dx.doi.org/10.1002/glia.22885] [PMID: 26148976] 
[378] 
Yang, Y.; Yang, L.Y.; Orban, L.; Cuylear, D.; Thompson, J.; Simon, B.; Yang, Y. Non-invasive vagus nerve stimulation reduces blood-brain barrier disruption in a rat model of ischemic stroke. Brain Stimul.,  2018, 11(4), 689-698.
[http://dx.doi.org/10.1016/j.brs.2018.01.034] [PMID: 29496430] 
[379] 
Huang, L.; Cao, W.; Deng, Y.; Zhu, G.; Han, Y.; Zeng, H. Hypertonic saline alleviates experimentally induced cerebral oedema through suppression of vascular endothelial growth factor and its receptor VEGFR2 expression in astrocytes. BMC Neurosci.,  2016, 17(1), 64.
[http://dx.doi.org/10.1186/s12868-016-0299-y] [PMID: 27733124] 
[380] 
Cao, C.; Yu, X.; Liao, Z.; Zhu, N.; Huo, H.; Wang, M.; Ji, G.; She, H.; Luo, Z.; Yue, S. Hypertonic saline reduces lipopolysaccharide-induced mouse brain edema through inhibiting aquaporin 4 expression. Crit. Care,  2012, 16(5), R186.
[http://dx.doi.org/10.1186/cc11670] [PMID: 23036239] 
[381] 
Oklinski, M.K.; Skowronski, M.T.; Skowronska, A.; Rützler, M.; Nørgaard, K.; Nieland, J.D.; Kwon, T-H.; Nielsen, S. Aquaporins in the Spinal Cord. Int. J. Mol. Sci.,  2016, 17(12), 2050.
[http://dx.doi.org/10.3390/ijms17122050] [PMID: 27941618] 
[382] 
Bonomini, F.; Rezzani, R. Aquaporin and blood brain barrier. Curr. Neuropharmacol.,  2010, 8(2), 92-96.
[http://dx.doi.org/10.2174/157015910791233132] [PMID: 21119879] 
Rights & Permissions Print Cite
Article Metrics
45
1
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/1570159X18666200528143301	Print ISSN 1570-159X
Publisher Name Bentham Science Publisher	Online ISSN 1875-6190
Current Neuropharmacology

The Stroke-Induced Blood-Brain Barrier Disruption: Current Progress of Inspection Technique, Mechanism, and Therapeutic Target

Abstract Play Pause

Graphical Abstract

Related Journals

Related Books

Related Articles

Abstract
