Therapeutic Hypothermia and Neuroprotection in Acute Neurological Disease

doi:10.2174/0929867326666190506124836
摘要

在许多研究神经疾病不同模型的实验室中，治疗性低温一直被证明是一种强大的神经保护剂。尽管这种疗法显示出了巨大的希望，但是在临床水平仍然存在挑战，限制了将其常规应用于每种病理状况的能力。为了克服低温疗法中涉及的问题，需要了解这种有吸引力的疗法。我们回顾了有关治疗性低温的方法学问题，介绍了各种急性脑损伤中治疗性降温的当前状态，并回顾了有关低温神经保护的许多潜在分子机制的文献。由于最近的工作表明可以使用药理学方法安全地降低体温，因此该方法对于许多临床应用而言可能是特别有吸引力的选择。由于体温过低会影响大脑病理生理学的多个方面，因此治疗性体温过低在基础研究中也可被视为神经保护模型，可用于确定潜在的治疗靶点。我们讨论如何重新研究
关键词: 低温，药理学诱导的低温，脑卒中，创伤性脑损伤，心脏骤停，缺氧缺血性脑病。
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[1] 
Kurisu, K.; Yenari, M.A. Therapeutic hypothermia for
ischemic stroke; Pathophysiology and future promise. Neuropharmacology, 2018. 134(pt. B), 302-309.
[PMID: 28830757] 
[2] 
Yenari, M.A.; Han, H.S. Neuroprotective mechanisms of hypothermia in brain ischaemia. Nat. Rev. Neurosci.,  2012, 13(4), 267-278.
[http://dx.doi.org/10.1038/nrn3174] [PMID:  22353781] 
[3] 
Bernard, S.A.; Gray, T.W.; Buist, M.D.; Jones, B.M.; Silvester, W.; Gutteridge, G.; Smith, K. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N. Engl. J. Med.,  2002, 346(8), 557-563.
[http://dx.doi.org/10.1056/NEJMoa003289] [PMID:  11856794] 
[4] 
Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N. Engl. J. Med.,  2002, 346(8), 549-556.
[http://dx.doi.org/10.1056/NEJMoa012689] [PMID:  11856793] 
[5] 
Azzopardi, D.V.; Strohm, B.; Edwards, A.D.; Dyet, L.; Halliday, H.L.; Juszczak, E.; Kapellou, O.; Levene, M.; Marlow, N.; Porter, E.; Thoresen, M.; Whitelaw, A.; Brocklehurst, P.; Group, T.S. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N. Engl. J. Med.,  2009, 361(14), 1349-1358.
[http://dx.doi.org/10.1056/NEJMoa0900854] [PMID:  19797281] 
[6] 
Gluckman, P.D.; Wyatt, J.S.; Azzopardi, D.; Ballard, R.; Edwards, A.D.; Ferriero, D.M.; Polin, R.A.; Robertson, C.M.; Thoresen, M.; Whitelaw, A.; Gunn, A.J. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: Multicentre randomised trial. Lancet,  2005, 365(9460), 663-670.
[http://dx.doi.org/10.1016/S0140-6736(05)17946-X] [PMID:  15721471] 
[7] 
Shankaran, S.; Laptook, A.R.; Ehrenkranz, R.A.; Tyson, J.E.; McDonald, S.A.; Donovan, E.F.; Fanaroff, A.A.; Poole, W.K.; Wright, L.L.; Higgins, R.D.; Finer, N.N.; Carlo, W.A.; Duara, S.; Oh, W.; Cotten, C.M.; Stevenson, D.K.; Stoll, B.J.; Lemons, J.A.; Guillet, R.; Jobe, A.H. National Institute of Child Health and Human Development Neonatal Research Network. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N. Engl. J. Med.,  2005, 353(15), 1574-1584.
[http://dx.doi.org/10.1056/NEJMcps050929] [PMID:  16221780] 
[8] 
van der Worp, H.B.; Macleod, M.R.; Bath, P.M.; Demotes, J.; Durand-Zaleski, I.; Gebhardt, B.; Gluud, C.; Kollmar, R.; Krieger, D.W.; Lees, K.R.; Molina, C.; Montaner, J.; Roine, R.O.; Petersson, J.; Staykov, D.; Szabo, I.; Wardlaw, J.M.; Schwab, S. EuroHYP-1 investigators. EuroHYP-1: European multicenter, randomized, phase III clinical trial of therapeutic hypothermia plus best medical treatment vs. best medical treatment alone for acute ischemic stroke. Int. J. Stroke,  2014, 9(5), 642-645.
[http://dx.doi.org/10.1111/ijs.12294] [PMID:  24828363] 
[9] 
Lyden, P.; Hemmen, T.; Grotta, J.; Rapp, K.; Ernstrom, K.; Rzesiewicz, T.; Parker, S.; Concha, M.; Hussain, S.; Agarwal, S.; Meyer, B.; Jurf, J.; Altafullah, I.; Raman, R. Collaborators. Results of the ICTUS 2 trial (intravascular cooling in the treatment of stroke 2). Stroke,  2016, 47(12), 2888-2895.
[http://dx.doi.org/10.1161/STROKEAHA.116.014200] [PMID:  27834742] 
[10] 
Chiu, A.W.; Hinson, H.E. Future directions for hypothermia following severe traumatic brian injury. Semin. Respir. Crit. Care Med.,  2017, 38(6), 768-774.
[http://dx.doi.org/10.1055/s-0037-1607989] [PMID:  29262434] 
[11] 
Watson, H.I.; Shepherd, A.A.; Rhodes, J.K.J.; Andrews, P.J.D. Revisited: A systematic review of therapeutic hypothermia for adult patients following traumatic brain injury. Crit. Care Med.,  2018, 46(6), 972-979.
[http://dx.doi.org/10.1097/CCM.0000000000003125] [PMID:  29601315] 
[12] 
Meinert, E.; Bell, M.J.; Buttram, S.; Kochanek, P.M.; Balasubramani, G.K.; Wisniewski, S.R.; Adelson, P.D. Pediatric Traumatic Brain Injury Consortium. Hypothermia Investigators. Hypothermia I: Initiating nutritional support before 72 hours is associated with favorable outcome after severe traumatic brain injury in children: A secondary analysis of a randomized, controlled trial of therapeutic hypothermia. Pediatr. Crit. Care Med.,  2018, 19(4), 345-352.
[http://dx.doi.org/10.1097/PCC.0000000000001471] [PMID:  29370008] 
[13] 
Davies, A.R. Hypothermia improves outcome from traumatic brain injury. Crit. Care Resusc.,  2005, 7(3), 238-243.
[PMID:  16545052] 
[14] 
Hong, J.M.; Lee, J.S.; Song, H.J.; Jeong, H.S.; Choi, H.A.; Lee, K. Therapeutic hypothermia after recanalization in patients with acute ischemic stroke. Stroke,  2014, 45(1), 134-140.
[http://dx.doi.org/10.1161/STROKEAHA.113.003143] [PMID:  24203846] 
[15] 
Hwang, Y.H.; Jeon, J.S.; Kim, Y.W.; Kang, D.H.; Kim, Y.S.; Liebeskind, D.S. Impact of immediate post-reperfusion cooling on outcome in patients with acute stroke and substantial ischemic changes. J. Neurointerv. Surg.,  2017, 9(1), 21-25.
[http://dx.doi.org/10.1136/neurintsurg-2015-012233] [PMID:  26940314] 
[16] 
van der Worp, H.B.; Macleod, M.R.; Kollmar, R. European Stroke Research Network for Hypothermia (EuroHYP). Therapeutic hypothermia for acute ischemic stroke: ready to start large randomized trials? J. Cereb. Blood Flow Metab.,  2010, 30(6), 1079-1093.
[http://dx.doi.org/10.1038/jcbfm.2010.44] [PMID:  20354545] 
[17] 
Krieger, D.W.; Yenari, M.A. Therapeutic hypothermia for acute ischemic stroke: what do laboratory studies teach us? Stroke,  2004, 35(6), 1482-1489.
[http://dx.doi.org/10.1161/01.STR.0000126118.44249.5c] [PMID:  15073396] 
[18] 
Wu, T.C.; Grotta, J.C. Hypothermia for acute ischaemic stroke. Lancet Neurol.,  2013, 12(3), 275-284.
[http://dx.doi.org/10.1016/S1474-4422(13)70013-9] [PMID:  23415567] 
[19] 
Lyden, P.D.; Krieger, D.; Yenari, M.; Dietrich, W.D. Therapeutic hypothermia for acute stroke. Int. J. Stroke,  2006, 1(1), 9-19.
[http://dx.doi.org/10.1111/j.1747-4949.2005.00011.x] [PMID:  18706063] 
[20] 
Huh, P.W.; Belayev, L.; Zhao, W.; Koch, S.; Busto, R.; Ginsberg, M.D. Comparative neuroprotective efficacy of prolonged moderate intraischemic and postischemic hypothermia in focal cerebral ischemia. J. Neurosurg.,  2000, 92(1), 91-99.
[http://dx.doi.org/10.3171/jns.2000.92.1.0091] [PMID:  10616087] 
[21] 
Maier, C.M.; Ahern, Kv.; Cheng, M.L.; Lee, J.E.; Yenari, M.A.; Steinberg, G.K. Optimal depth and duration of mild hypothermia in a focal model of transient cerebral ischemia: effects on neurologic outcome, infarct size, apoptosis, and inflammation. Stroke,  1998, 29(10), 2171-2180.
[http://dx.doi.org/10.1161/01.STR.29.10.2171] [PMID:  9756600] 
[22] 
Clark, D.L.; Penner, M.; Orellana-Jordan, I.M.; Colbourne, F. Comparison of 12, 24 and 48 h of systemic hypothermia on outcome after permanent focal ischemia in rat. Exp. Neurol.,  2008, 212(2), 386-392.
[http://dx.doi.org/10.1016/j.expneurol.2008.04.016] [PMID:  18538766] 
[23] 
Lawrence, E.J.; Dentcheva, E.; Curtis, K.M.; Roberts, V.L.; Siman, R.; Neumar, R.W. Neuroprotection with delayed initiation of prolonged hypothermia after in vitro transient global brain ischemia. Resuscitation,  2005, 64(3), 383-388.
[http://dx.doi.org/10.1016/j.resuscitation.2004.07.016] [PMID:  15733770] 
[24] 
Colbourne, F.; Corbett, D. Delayed and prolonged post-ischemic hypothermia is neuroprotective in the gerbil. Brain Res.,  1994, 654(2), 265-272.
[http://dx.doi.org/10.1016/0006-8993(94)90488-X] [PMID:  7987676] 
[25] 
Shackelford, R.T.; Hegedus, S.A. Factors affecting cerebral blood flow--experimental review: sympathectomy, hypothermia, CO2 inhalation and pavarine. Ann. Surg.,  1966, 163(5), 771-777.
[http://dx.doi.org/10.1097/00000658-196605000-00014] [PMID:  5930460] 
[26] 
Hägerdal, M.; Harp, J.; Nilsson, L.; Siesjö, B.K. The effect of induced hypothermia upon oxygen consumption in the rat brain. J. Neurochem.,  1975, 24(2), 311-316.
[http://dx.doi.org/10.1111/j.1471-4159.1975.tb11881.x] [PMID:  1113108] 
[27] 
Lee, J.M.; Zipfel, G.J.; Choi, D.W. The changing landscape of ischaemic brain injury mechanisms. Nature,  1999, 399(6738)(Suppl.), A7-A14.
[http://dx.doi.org/10.1038/399a007] [PMID:  10392575] 
[28] 
Colbourne, F.; Li, H.; Buchan, A.M. Indefatigable CA1 sector neuroprotection with mild hypothermia induced 6 hours after severe forebrain ischemia in rats. J. Cereb. Blood Flow Metab.,  1999, 19(7), 742-749.
[http://dx.doi.org/10.1097/00004647-199907000-00003] [PMID:  10413028] 
[29] 
Liu, K.; Khan, H.; Geng, X.; Zhang, J.; Ding, Y. Pharmacological hypothermia: a potential for future stroke therapy? Neurol. Res.,  2016, 38(6), 478-490.
[http://dx.doi.org/10.1080/01616412.2016.1187826] [PMID:  27320243] 
[30] 
Rawls, S.M.; Cabassa, J.; Geller, E.B.; Adler, M.W. CB1 receptors in the preoptic anterior hypothalamus regulate WIN 55212-2 [(4,5-dihydro-2-methyl-4(4-morpholinylmethyl)-1-(1-naphthalenyl-carbonyl)-6H-pyrrolo[3,2,1ij]quinolin-6-one]-induced hypothermia. J. Pharmacol. Exp. Ther.,  2002, 301(3), 963-968.
[http://dx.doi.org/10.1124/jpet.301.3.963] [PMID:  12023525] 
[31] 
Gerdeman, G.; Lovinger, D.M. CB1 cannabinoid receptor inhibits synaptic release of glutamate in rat dorsolateral striatum. J. Neurophysiol.,  2001, 85(1), 468-471.
[http://dx.doi.org/10.1152/jn.2001.85.1.468] [PMID:  11152748] 
[32] 
Fernández-López, D.; Faustino, J.; Derugin, N.; Wendland, M.; Lizasoain, I.; Moro, M.A.; Vexler, Z.S. Reduced infarct size and accumulation of microglia in rats treated with WIN 55,212-2 after neonatal stroke. Neuroscience,  2012, 207, 307-315.
[http://dx.doi.org/10.1016/j.neuroscience.2012.01.008] [PMID:  22285309] 
[33] 
Chi, O.Z.; Barsoum, S.; Grayson, J.; Hunter, C.; Liu, X.; Weiss, H.R. Effects of cannabinoid receptor agonist WIN 55,212-2 on blood-brain barrier disruption in focal cerebral ischemia in rats. Pharmacology,  2012, 89(5-6), 333-338.
[http://dx.doi.org/10.1159/000338755] [PMID:  22678129] 
[34] 
Bonfils, P.K.; Reith, J.; Hasseldam, H.; Johansen, F.F. Estimation of the hypothermic component in neuroprotection provided by cannabinoids following cerebral ischemia. Neurochem. Int.,  2006, 49(5), 508-518.
[http://dx.doi.org/10.1016/j.neuint.2006.03.015] [PMID:  16730099] 
[35] 
Leker, R.R.; Gai, N.; Mechoulam, R.; Ovadia, H. Drug-induced hypothermia reduces ischemic damage: effects of the cannabinoid HU-210. Stroke,  2003, 34(8), 2000-2006.
[http://dx.doi.org/10.1161/01.STR.0000079817.68944.1E] [PMID:  12829867] 
[36] 
Murakami, K.; Suzuki, M.; Suzuki, N.; Hamajo, K.; Tsukamoto, T.; Shimojo, M. Cerebroprotective effects of TAK-937, a novel cannabinoid receptor agonist, in permanent and thrombotic focal cerebral ischemia in rats: therapeutic time window, combination with t-PA and efficacy in aged rats. Brain Res.,  2013, 1526, 84-93.
[http://dx.doi.org/10.1016/j.brainres.2013.06.014] [PMID:  23791950] 
[37] 
Caterina, M.J.; Schumacher, M.A.; Tominaga, M.; Rosen, T.A.; Levine, J.D.; Julius, D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature,  1997, 389(6653), 816-824.
[http://dx.doi.org/10.1038/39807] [PMID:  9349813] 
[38] 
Fosgerau, K.; Weber, U.J.; Gotfredsen, J.W.; Jayatissa, M.; Buus, C.; Kristensen, N.B.; Vestergaard, M.; Teschendorf, P.; Schneider, A.; Hansen, P.; Raunsø, J.; Køber, L.; Torp-Pedersen, C.; Videbaek, C. Drug-induced mild therapeutic hypothermia obtained by administration of a transient receptor potential vanilloid type 1 agonist. BMC Cardiovasc. Disord.,  2010, 10, 51.
[http://dx.doi.org/10.1186/1471-2261-10-51] [PMID:  20932337] 
[39] 
Baker, A.K.; Meert, T.F. Functional effects of systemically administered agonists and antagonists of mu, delta, and kappa opioid receptor subtypes on body temperature in mice. J. Pharmacol. Exp. Ther.,  2002, 302(3), 1253-1264.
[http://dx.doi.org/10.1124/jpet.102.037655] [PMID:  12183687] 
[40] 
Torup, L.; Borsdal, J.; Sager, T. Neuroprotective effect of the neurotensin analogue JMV-449 in a mouse model of permanent middle cerebral ischaemia. Neurosci. Lett.,  2003, 351(3), 173-176.
[http://dx.doi.org/10.1016/j.neulet.2003.08.008] [PMID:  14623134] 
[41] 
Katz, L.M.; Wang, Y.; McMahon, B. Richelson, E Neurotensin analog nt69l induces rapid and prolonged hypothermia after hypoxic ischemia. Acad. Emerg. Med.,  2001, 8, 1115-1121.
[http://dx.doi.org/10.1111/j.1553-2712.2001.tb01126.x] 
[42] 
Doyle, K.P.; Suchland, K.L.; Ciesielski, T.M.; Lessov, N.S.; Grandy, D.K.; Scanlan, T.S.; Stenzel-Poore, M.P. Novel thyroxine derivatives, thyronamine and 3-iodothyronamine, induce transient hypothermia and marked neuroprotection against stroke injury. Stroke,  2007, 38(9), 2569-2576.
[http://dx.doi.org/10.1161/STROKEAHA.106.480277] [PMID:  17690312] 
[43] 
Johansen, F.F.; Hasseldam, H.; Rasmussen, R.S.; Bisgaard, A.S.; Bonfils, P.K.; Poulsen, S.S.; Hansen-Schwartz, J. Drug-induced hypothermia as beneficial treatment before and after cerebral ischemia. Pathobiology,  2014, 81, 42-52.
[http://dx.doi.org/10.1159/000352026] 
[44] 
O’Neill, M.J.; Hicks, C.A.; Ward, M.A.; Cardwell, G.P.; Reymann, J.M.; Allain, H.; Bentué-Ferrer, D. Dopamine D2 receptor agonists protect against ischaemia-induced hippocampal neurodegeneration in global cerebral ischaemia. Eur. J. Pharmacol.,  1998, 352(1), 37-46.
[http://dx.doi.org/10.1016/S0014-2999(98)00333-1] [PMID:  9718265] 
[45] 
David, H.N.; Haelewyn, B.; Chazalviel, L.; Lecocq, M.; Degoulet, M.; Risso, J.J.; Abraini, J.H. Post-ischemic helium provides neuroprotection in rats subjected to middle cerebral artery occlusion-induced ischemia by producing hypothermia. J. Cereb. Blood Flow Metab.,  2009, 29(6), 1159-1165.
[http://dx.doi.org/10.1038/jcbfm.2009.40] [PMID:  19384333] 
[46] 
Sheng, S.P.; Lei, B.; James, M.L.; Lascola, C.D.; Venkatraman, T.N.; Jung, J.Y.; Maze, M.; Franks, N.P.; Pearlstein, R.D.; Sheng, H.; Warner, D.S. Xenon neuroprotection in experimental stroke: interactions with hypothermia and intracerebral hemorrhage. Anesthesiology,  2012, 117(6), 1262-1275.
[http://dx.doi.org/10.1097/ALN.0b013e3182746b81] [PMID:  23143806] 
[47] 
Zhang, F.; Wang, S.; Luo, Y.; Ji, X.; Nemoto, E.M.; Chen, J. When hypothermia meets hypotension and hyperglycemia: the diverse effects of adenosine 5′-monophosphate on cerebral ischemia in rats. J. Cereb. Blood Flow Metab.,  2009, 29(5), 1022-1034.
[http://dx.doi.org/10.1038/jcbfm.2009.28] [PMID:  19319149] 
[48] 
Zhang, M.; Li, W.; Niu, G.; Leak, R.K.; Chen, J.; Zhang, F. ATP induces mild hypothermia in rats but has a strikingly detrimental impact on focal cerebral ischemia. J. Cereb. Blood Flow Metab.,  2013, 33(1), 33.
[http://dx.doi.org/10.1038/jcbfm.2012.146] [PMID:  23072747] 
[49] 
Zhang, Z.; Zhang, L.; Ding, Y.; Han, Z.; Ji, X. Effects of therapeutic hypothermia combined with other neuroprotective strategies on ischemic stroke: Review of evidence. Aging Dis.,  2018, 9(3), 507-522.
[http://dx.doi.org/10.14336/AD.2017.0628] [PMID:  29896438] 
[50] 
Zhu, S.; Gao, X.; Huang, K.; Gu, Y.; Hu, Y.; Wu, Y.; Ji, Z.; Wang, Q.; Pan, S. Glibenclamide enhances the therapeutic benefits of early hypothermia after severe stroke in rats. Aging Dis.,  2018, 9(4), 685-695.
[http://dx.doi.org/10.14336/AD.2017.0927] [PMID:  30090656] 
[51] 
Nakayama, S.; Taguchi, N.; Isaka, Y.; Nakamura, T.; Tanaka, M. Glibenclamide and therapeutic hypothermia have comparable effect on attenuating global cerebral edema following experimental cardiac arrest. Neurocrit. Care,  2018, 29(1), 119-127.
[http://dx.doi.org/10.1007/s12028-017-0479-3] [PMID:  29150777] 
[52] 
Huang, K.; Wang, Z.; Gu, Y.; Hu, Y.; Ji, Z.; Wang, S.; Lin, Z.; Li, X.; Xie, Z.; Pan, S. Glibenclamide is comparable to target temperature management in improving survival and neurological outcome after asphyxial cardiac arrest in rats. J. Am. Heart Assoc.,  2016, 5(7), 5.
[http://dx.doi.org/10.1161/JAHA.116.003465] [PMID:  27413041] 
[53] 
Green, E.J.; Pazos, A.J.; Dietrich, W.D.; McCabe, P.M.; Schneiderman, N.; Lin, B.; Busto, R.; Globus, M.Y.; Ginsberg, M.D. Combined postischemic hypothermia and delayed MK-801 treatment attenuates neurobehavioral deficits associated with transient global ischemia in rats. Brain Res.,  1995, 702(1-2), 145-152.
[http://dx.doi.org/10.1016/0006-8993(95)01034-1] [PMID:  8846069] 
[54] 
Dietrich, W.D.; Lin, B.; Globus, M.Y.; Green, E.J.; Ginsberg, M.D.; Busto, R. Effect of delayed MK-801 (dizocilpine) treatment with or without immediate postischemic hypothermia on chronic neuronal survival after global forebrain ischemia in rats. J. Cereb. Blood Flow Metab.,  1995, 15(6), 960-968.
[http://dx.doi.org/10.1038/jcbfm.1995.122] [PMID:  7593357] 
[55] 
Alkan, T.; Kahveci, N.; Buyukuysal, L.; Korfali, E.; Ozluk, K. Neuroprotective effects of MK 801 and hypothermia used alone and in combination in hypoxic-ischemic brain injury in neonatal rats. Arch. Physiol. Biochem.,  2001, 109(2), 135-144.
[http://dx.doi.org/10.1076/apab.109.2.135.4271] [PMID:  11780774] 
[56] 
Shuaib, A.; Waqar, T.; Wishart, T.; Kanthan, R. Post-ischemic therapy with CGS-19755 (alone or in combination with hypothermia) in gerbils. Neurosci. Lett.,  1995, 191(1-2), 87-90.
[http://dx.doi.org/10.1016/0304-3940(95)11567-0] [PMID:  7659298] 
[57] 
Shuaib, A.; Ijaz, S.; Mazagri, R.; Senthilsevlvan, A. CGS-19755 is neuroprotective during repetitive ischemia: This effect is significantly enhanced when combined with hypothermia. Neuroscience,  1993, 56(4), 915-920.
[http://dx.doi.org/10.1016/0306-4522(93)90137-5] [PMID:  8284043] 
[58] 
Campbell, K.; Meloni, B.P.; Knuckey, N.W. Combined magnesium and mild hypothermia (35 degrees C) treatment reduces infarct volumes after permanent middle cerebral artery occlusion in the rat at 2 and 4, but not 6 h. Brain Res.,  2008, 1230, 258-264.
[http://dx.doi.org/10.1016/j.brainres.2008.06.110] [PMID:  18644354] 
[59] 
Song, W.; Wu, Y.M.; Ji, Z.; Ji, Y.B.; Wang, S.N.; Pan, S.Y. Intra-carotid cold magnesium sulfate infusion induces selective cerebral hypothermia and neuroprotection in rats with transient middle cerebral artery occlusion. Neurol. Sci.,  2013, 34, 479-486.
[http://dx.doi.org/10.1007/s10072-012-1064-3] 
[60] 
Meloni, B.P.; Cross, J.L.; Brookes, L.M.; Clark, V.W.; Campbell, K.; Knuckey, N.W. FAST-Mag protocol with or without mild hypothermia (35°C) does not improve outcome after permanent MCAO in rats. Magnes. Res.,  2013, 26(2), 67-73.
[PMID:  23816810] 
[61] 
Nito, C.; Kamiya, T.; Ueda, M.; Arii, T.; Katayama, Y. Mild hypothermia enhances the neuroprotective effects of FK506 and expands its therapeutic window following transient focal ischemia in rats. Brain Res.,  2004, 1008(2), 179-185.
[http://dx.doi.org/10.1016/j.brainres.2004.02.031] [PMID:  15145754] 
[62] 
Zhou, H.; Huang, S.; Sunnassee, G.; Guo, W.; Chen, J.; Guo, Y.; Tan, S. Neuroprotective effects of adjunctive treatments for acute stroke thrombolysis: a review of clinical evidence. Int. J. Neurosci.,  2017, 127(11), 1036-1046.
[http://dx.doi.org/10.1080/00207454.2017.1286338] [PMID:  28110588] 
[63] 
Nagel, S.; Su, Y.; Horstmann, S.; Heiland, S.; Gardner, H.; Koziol, J.; Martinez-Torres, F.J.; Wagner, S. Minocycline and hypothermia for reperfusion injury after focal cerebral ischemia in the rat: effects on BBB breakdown and MMP expression in the acute and subacute phase. Brain Res.,  2008, 1188, 198-206.
[http://dx.doi.org/10.1016/j.brainres.2007.10.052] [PMID:  18031717] 
[64] 
Nito, C; Kamiya, T; Amemiya, S; Katoh, K; Katayama, Y Y
The neuroprotective effect of a free radical scavenger and
mild hypothermia following transient focal ischemia in rats. Acta neurochirurgica Supplement,  2003, 86, 199-203.
[http://dx.doi.org/10.1007/978-3-7091-0651-8_43] 
[65] 
Amiri-Nikpour, M.R.; Nazarbaghi, S.; Hamdi-Holasou, M.; Rezaei, Y. An open-label evaluator-blinded clinical study of minocycline neuroprotection in ischemic stroke: gender-dependent effect. Acta Neurol. Scand.,  2015, 131(1), 45-50.
[http://dx.doi.org/10.1111/ane.12296] [PMID:  25155474] 
[66] 
Zhu, C.; Wang, X.; Xu, F.; Qiu, L.; Cheng, X.; Simbruner, G.; Blomgren, K. Intraischemic mild hypothermia prevents neuronal cell death and tissue loss after neonatal cerebral hypoxia-ischemia. Eur. J. Neurosci.,  2006, 23(2), 387-393.
[http://dx.doi.org/10.1111/j.1460-9568.2005.04581.x] [PMID:  16420446] 
[67] 
van der Worp, H.B.; Sena, E.S.; Donnan, G.A.; Howells, D.W.; Macleod, M.R. Hypothermia in animal models of acute ischaemic stroke: a systematic review and meta-analysis. Brain,  2007, 130(Pt 12), 3063-3074.
[http://dx.doi.org/10.1093/brain/awm083] [PMID:  17478443] 
[68] 
De Georgia, M.A.; Krieger, D.W.; Abou-Chebl, A.; Devlin, T.G.; Jauss, M.; Davis, S.M.; Koroshetz, W.J.; Rordorf, G.; Warach, S. Cooling for Acute Ischemic Brain Damage (COOL AID): a feasibility trial of endovascular cooling. Neurology,  2004, 63(2), 312-317.
[http://dx.doi.org/10.1212/01.WNL.0000129840.66938.75] [PMID:  15277626] 
[69] 
Hemmen, T.M.; Raman, R.; Guluma, K.Z.; Meyer, B.C.; Gomes, J.A.; Cruz-Flores, S.; Wijman, C.A.; Rapp, K.S.; Grotta, J.C.; Lyden, P.D. Intravenous thrombolysis plus hypothermia for acute treatment of ischemic stroke (ICTuS-L): final results. Stroke,  2010, 41(10), 2265-2270.
[http://dx.doi.org/10.1161/STROKEAHA.110.592295] [PMID:  20724711] 
[70] 
Kawai, N.; Kawanishi, M.; Okauchi, M.; Nagao, S. Effects of hypothermia on thrombin-induced brain edema formation. Brain Res.,  2001, 895(1-2), 50-58.
[http://dx.doi.org/10.1016/S0006-8993(01)02026-1] [PMID:  11259759] 
[71] 
Dai, D.W.; Wang, D.S.; Li, K.S.; Mao, Y.; Zhang, L.M.; Duan, S.R.; Sheng, L. Effect of local mild hypothermia on expression of aquaporin-4 following intracerebral hemorrhage in rats. Zhonghua Yi Xue Za Zhi,  2006, 86(13), 906-910.
[PMID:  16759517] 
[72] 
Fingas, M.; Clark, D.L.; Colbourne, F. The effects of selective brain hypothermia on intracerebral hemorrhage in rats. Exp. Neurol.,  2007, 208(2), 277-284.
[http://dx.doi.org/10.1016/j.expneurol.2007.08.018] [PMID:  17927984] 
[73] 
MacLellan, C.L.; Davies, L.M.; Fingas, M.S.; Colbourne, F. The influence of hypothermia on outcome after intracerebral hemorrhage in rats. Stroke,  2006, 37(5), 1266-1270.
[http://dx.doi.org/10.1161/01.STR.0000217268.81963.78] [PMID:  16574928] 
[74] 
Melmed, K.R.; Lyden, P.D. Meta-analysis of pre-clinical trials of therapeutic hypothermia for intracerebral hemorrhage. Ther. Hypothermia Temp. Manag.,  2017, 7(3), 141-146.
[http://dx.doi.org/10.1089/ther.2016.0033] [PMID:  27906602] 
[75] 
Preston, E.; Webster, J. A two-hour window for hypothermic modulation of early events that impact delayed opening of the rat blood-brain barrier after ischemia. Acta Neuropathol.,  2004, 108(5), 406-412.
[http://dx.doi.org/10.1007/s00401-004-0905-4] [PMID:  15351891] 
[76] 
Yao, Z.; You, C.; He, M. Effect and feasibility of therapeutic
hypothermia in patients with hemorrhagic stroke: A systematic
review and meta-analysis., 2018.
[http://dx.doi.org/10.1016/j.wneu.2018.01.020] 
[77] 
Kollmar, R.; Staykov, D.; Dörfler, A.; Schellinger, P.D.; Schwab, S.; Bardutzky, J. Hypothermia reduces perihemorrhagic edema after intracerebral hemorrhage. Stroke,  2010, 41(8), 1684-1689.
[http://dx.doi.org/10.1161/STROKEAHA.110.587758] [PMID:  20616317] 
[78] 
Rincon, F.; Friedman, D.P.; Bell, R.; Mayer, S.A.; Bray, P.F. Targeted temperature management after intracerebral hemorrhage (TTM-ICH): methodology of a prospective randomized clinical trial. Int. J. Stroke,  2014, 9(5), 646-651.
[http://dx.doi.org/10.1111/ijs.12220] [PMID:  24450819] 
[79] 
Kollmar, R.; Juettler, E.; Huttner, H.B.; Dörfler, A.; Staykov, D.; Kallmuenzer, B.; Schmutzhard, E.; Schwab, S.; Broessner, G. Cooling in intracerebral hemorrhage (CINCH) trial: protocol of a randomized German-Austrian clinical trial. Int. J. Stroke,  2012, 7(2), 168-172.
[http://dx.doi.org/10.1111/j.1747-4949.2011.00707.x] [PMID:  22264371] 
[80] 
Török, E.; Klopotowski, M.; Trabold, R.; Thal, S.C.; Plesnila, N.; Schöller, K. Mild hypothermia (33 degrees C) reduces intracranial hypertension and improves functional outcome after subarachnoid hemorrhage in rats. Neurosurgery,  2009, 65(2), 352-359.
[http://dx.doi.org/10.1227/01.NEU.0000345632.09882.FF] [PMID:  19625915] 
[81] 
Schubert, G.A.; Poli, S.; Mendelowitsch, A.; Schilling, L.; Thomé, C. Hypothermia reduces early hypoperfusion and metabolic alterations during the acute phase of massive subarachnoid hemorrhage: A laser-Doppler-flowmetry and microdialysis study in rats. J. Neurotrauma,  2008, 25(5), 539-548.
[http://dx.doi.org/10.1089/neu.2007.0500] [PMID:  18352824] 
[82] 
Kawamura, Y.; Yamada, K.; Masago, A.; Katano, H.; Matsumoto, T.; Mase, M. Hypothermia modulates induction of hsp70 and c-jun mRNA in the rat brain after subarachnoid hemorrhage. J. Neurotrauma,  2000, 17(3), 243-250.
[http://dx.doi.org/10.1089/neu.2000.17.243] [PMID:  10757329] 
[83] 
Muroi, C.; Frei, K.; El Beltagy, M.; Cesnulis, E.; Yonekawa, Y.; Keller, E. Combined therapeutic hypothermia and barbiturate coma reduces interleukin-6 in the cerebrospinal fluid after aneurysmal subarachnoid hemorrhage. J. Neurosurg. Anesthesiol.,  2008, 20(3), 193-198.
[http://dx.doi.org/10.1097/ANA.0b013e31817996bf] [PMID:  18580350] 
[84] 
Todd, M.M.; Hindman, B.J.; Clarke, W.R.; Torner, J.C. Intraoperative Hypothermia for Aneurysm Surgery Trial (IHAST) Investigators. Mild intraoperative hypothermia during surgery for intracranial aneurysm. N. Engl. J. Med.,  2005, 352(2), 135-145.
[http://dx.doi.org/10.1056/NEJMoa040975] [PMID:  15647576] 
[85] 
Seule, M.A.; Muroi, C.; Mink, S.; Yonekawa, Y.; Keller, E. Therapeutic hypothermia in patients with aneurysmal subarachnoid hemorrhage, refractory intracranial hypertension, or cerebral vasospasm. Neurosurgery,  2009, 64(1), 86-92.
[http://dx.doi.org/10.1227/01.NEU.0000336312.32773.A0] [PMID:  19050656] 
[86] 
Dietrich, W.D.; Bramlett, H.M. Therapeutic hypothermia
and targeted temperature management in traumatic brain injury:
Clinical challenges for successful translation. Brain
Res, 2016. 1640(Pt A), 94-103.
[http://dx.doi.org/10.1016/j.brainres.2015.12.034] [PMID: 26746342] 
[87] 
Andresen, M.; Gazmuri, J.T.; Marín, A.; Regueira, T.; Rovegno, M. Therapeutic hypothermia for acute brain injuries. Scand. J. Trauma Resusc. Emerg. Med.,  2015, 23, 42.
[http://dx.doi.org/10.1186/s13049-015-0121-3] [PMID:  26043908] 
[88] 
Clifton, G.L.; Jiang, J.Y.; Lyeth, B.G.; Jenkins, L.W.; Hamm, R.J.; Hayes, R.L. Marked protection by moderate hypothermia after experimental traumatic brain injury. J. Cereb. Blood Flow Metab.,  1991, 11(1), 114-121.
[http://dx.doi.org/10.1038/jcbfm.1991.13] [PMID:  1983995] 
[89] 
Bramlett, H.M.; Dietrich, W.D.; Green, E.J.; Busto, R. Chronic histopathological consequences of fluid-percussion brain injury in rats: effects of post-traumatic hypothermia. Acta Neuropathol.,  1997, 93(2), 190-199.
[http://dx.doi.org/10.1007/s004010050602] [PMID:  9039468] 
[90] 
Dietrich, W.D.; Alonso, O.; Busto, R.; Globus, M.Y.; Ginsberg, M.D. Post-traumatic brain hypothermia reduces histopathological damage following concussive brain injury in the rat. Acta Neuropathol.,  1994, 87(3), 250-258.
[http://dx.doi.org/10.1007/BF00296740] [PMID:  8009957] 
[91] 
Bramlett, H.M.; Dietrich, W.D. The effects of posttraumatic hypothermia on diffuse axonal injury following parasaggital fluid percussion brain injury in rats. Ther. Hypothermia Temp. Manag.,  2012, 2(1), 14-23.
[http://dx.doi.org/10.1089/ther.2012.0002] [PMID:  23420536] 
[92] 
Ma, M.; Matthews, B.T.; Lampe, J.W.; Meaney, D.F.; Shofer, F.S.; Neumar, R.W. Immediate short-duration hypothermia provides long-term protection in an in vivo model of traumatic axonal injury. Exp. Neurol.,  2009, 215(1), 119-127.
[http://dx.doi.org/10.1016/j.expneurol.2008.09.024] [PMID:  18977220] 
[93] 
Dietrich, W.D.; Bramlett, H.M. The evidence for hypothermia as a neuroprotectant in traumatic brain injury. Neurotherapeutics,  2010, 7(1), 43-50.
[http://dx.doi.org/10.1016/j.nurt.2009.10.015] [PMID:  20129496] 
[94] 
Marion, D.W.; Penrod, L.E.; Kelsey, S.F.; Obrist, W.D.; Kochanek, P.M.; Palmer, A.M.; Wisniewski, S.R.; DeKosky, S.T. Treatment of traumatic brain injury with moderate hypothermia. N. Engl. J. Med.,  1997, 336(8), 540-546.
[http://dx.doi.org/10.1056/NEJM199702203360803] [PMID:  9023090] 
[95] 
Jiang, J.Y.; Xu, W.; Li, W.P.; Gao, G.Y.; Bao, Y.H.; Liang, Y.M.; Luo, Q.Z. Effect of long-term mild hypothermia or short-term mild hypothermia on outcome of patients with severe traumatic brain injury. J. Cereb. Blood Flow Metab.,  2006, 26(6), 771-776.
[http://dx.doi.org/10.1038/sj.jcbfm.9600253] [PMID:  16306933] 
[96] 
Adelson, P.D.; Wisniewski, S.R.; Beca, J.; Brown, S.D.; Bell, M.; Muizelaar, J.P.; Okada, P.; Beers, S.R.; Balasubramani, G.K.; Hirtz, D. Paediatric Traumatic Brain Injury, C. Paediatric Traumatic Brain Injury Consortium. Comparison of hypothermia and normothermia after severe traumatic brain injury in children (Cool Kids): a phase 3, randomised controlled trial. Lancet Neurol.,  2013, 12(6), 546-553.
[http://dx.doi.org/10.1016/S1474-4422(13)70077-2] [PMID:  23664370] 
[97] 
Beca, J.; McSharry, B.; Erickson, S.; Yung, M.; Schibler, A.; Slater, A.; Wilkins, B.; Singhal, A.; Williams, G.; Sherring, C.; Butt, W. Pediatric Study Group of the Australia and New Zealand Intensive Care Society Clinical Trials Group. Pediatric Study Group of the A, New Zealand Intensive Care Society Clinical Trials G: Hypothermia for traumatic brain injury in children-a phase ii randomized controlled trial. Crit. Care Med.,  2015, 43(7), 1458-1466.
[http://dx.doi.org/10.1097/CCM.0000000000000947] [PMID:  25803648] 
[98] 
Lei, J.; Gao, G.; Mao, Q.; Feng, J.; Wang, L.; You, W.; Jiang, J. LTH-1 trial collaborators. Rationale, methodology, and implementation of a nationwide multicenter randomized controlled trial of long-term mild hypothermia for severe traumatic brain injury (the LTH-1 trial). Contemp. Clin. Trials,  2015, 40, 9-14.
[http://dx.doi.org/10.1016/j.cct.2014.11.008] [PMID:  25460339] 
[99] 
Nichol, A.; Gantner, D.; Presneill, J.; Murray, L.; Trapani, T.; Bernard, S.; Cameron, P.; Capellier, G.; Forbes, A.; McArthur, C.; Newby, L.; Rashford, S.; Rosenfeld, J.V.; Smith, T.; Stephenson, M.; Varma, D.; Walker, T.; Webb, S.; Cooper, D.J. Protocol for a multicentre randomised controlled trial of early and sustained prophylactic hypothermia in the management of traumatic brain injury. Crit. Care Resusc.,  2015, 17(2), 92-100.
[PMID:  26017126] 
[100] 
Andrews, P.J.; Harris, B.A.; Murray, G.D. Hypothermia for intracranial hypertension after traumatic brain injury. N. Engl. J. Med.,  2016, 374(14), 1385.
[PMID:  27050212] 
[101] 
Flynn, L.M.; Rhodes, J.; Andrews, P.J. Therapeutic hypothermia reduces intracranial pressure and partial brain oxygen tension in patients with severe traumatic brain injury: Preliminary data from the eurotherm3235 trial. Ther. Hypothermia Temp. Manag.,  2015, 5(3), 143-151.
[http://dx.doi.org/10.1089/ther.2015.0002] [PMID:  26060880] 
[102] 
Martirosyan, N.L.; Patel, A.A.; Carotenuto, A.; Kalani, M.Y.; Bohl, M.A.; Preul, M.C.; Theodore, N. The role of therapeutic hypothermia in the management of acute spinal cord injury. Clin. Neurol. Neurosurg.,  2017, 154, 79-88.
[http://dx.doi.org/10.1016/j.clineuro.2017.01.002] [PMID:  28131967] 
[103] 
Ahmad, F.U.; Wang, M.Y.; Levi, A.D. Hypothermia for acute spinal cord injury--a review. World Neurosurg.,  2014, 82(1-2), 207-214.
[http://dx.doi.org/10.1016/j.wneu.2013.01.008] [PMID:  23298671] 
[104] 
Yamamoto, K.; Ishikawa, T.; Sakabe, T.; Taguchi, T.; Kawai, S.; Marsala, M. The hydroxyl radical scavenger Nicaraven inhibits glutamate release after spinal injury in rats. Neuroreport,  1998, 9(7), 1655-1659.
[http://dx.doi.org/10.1097/00001756-199805110-00072] [PMID:  9631482] 
[105] 
Yu, W.R.; Westergren, H.; Farooque, M.; Holtz, A.; Olsson, Y. Systemic hypothermia following spinal cord compression injury in the rat: an immunohistochemical study on MAP 2 with special reference to dendrite changes. Acta Neuropathol.,  2000, 100(5), 546-552.
[http://dx.doi.org/10.1007/s004010000206] [PMID:  11045677] 
[106] 
Yu, W.R.; Westergren, H.; Farooque, M.; Holtz, A.; Olsson, Y. Systemic hypothermia following compression injury of rat spinal cord: reduction of plasma protein extravasation demonstrated by immunohistochemistry. Acta Neuropathol.,  1999, 98(1), 15-21.
[http://dx.doi.org/10.1007/s004010051046] [PMID:  10412796] 
[107] 
Chatzipanteli, K.; Yanagawa, Y.; Marcillo, A.E.; Kraydieh, S.; Yezierski, R.P.; Dietrich, W.D. Posttraumatic hypothermia reduces polymorphonuclear leukocyte accumulation following spinal cord injury in rats. J. Neurotrauma,  2000, 17(4), 321-332.
[http://dx.doi.org/10.1089/neu.2000.17.321] [PMID:  10776915] 
[108] 
Westergren, H.; Farooque, M.; Olsson, Y.; Holtz, A. Spinal cord blood flow changes following systemic hypothermia and spinal cord compression injury: an experimental study in the rat using Laser-Doppler flowmetry. Spinal Cord,  2001, 39(2), 74-84.
[http://dx.doi.org/10.1038/sj.sc.3101127] [PMID:  11402362] 
[109] 
Zager, E.L.; Ames, A., III Reduction of cellular energy requirements. Screening for agents that may protect against CNS ischemia. J. Neurosurg.,  1988, 69(4), 568-579.
[http://dx.doi.org/10.3171/jns.1988.69.4.0568] [PMID:  3418390] 
[110] 
Ji, X.; Luo, Y.; Ling, F.; Stetler, R.A.; Lan, J.; Cao, G.; Chen, J. Mild hypothermia diminishes oxidative DNA damage and pro-death signaling events after cerebral ischemia: A mechanism for neuroprotection. Front. Biosci.,  2007, 12, 1737-1747.
[http://dx.doi.org/10.2741/2185] 
[111] 
Ohmura, A.; Nakajima, W.; Ishida, A.; Yasuoka, N.; Kawamura, M.; Miura, S.; Takada, G. Prolonged hypothermia protects neonatal rat brain against hypoxic-ischemia by reducing both apoptosis and necrosis. Brain Dev.,  2005, 27(7), 517-526.
[http://dx.doi.org/10.1016/j.braindev.2005.01.004] [PMID:  15899566] 
[112] 
Hägerdal, M.; Harp, J.; Siesjö, B.K. Effect of hypothermia upon organic phosphates, glycolytic metabolites, citric acid cycle intermediates and associated amino acids in rat cerebral cortex. J. Neurochem.,  1975, 24(4), 743-748.
[http://dx.doi.org/10.1111/j.1471-4159.1975.tb11673.x] [PMID:  1123628] 
[113] 
Ehrlich, M.P.; McCullough, J.N.; Zhang, N.; Weisz, D.J.; Juvonen, T.; Bodian, C.A.; Griepp, R.B. Effect of hypothermia on cerebral blood flow and metabolism in the pig. Ann. Thorac. Surg.,  2002, 73(1), 191-197.
[http://dx.doi.org/10.1016/S0003-4975(01)03273-8] [PMID:  11834009] 
[114] 
Matsumoto, M.; Scheller, M.S.; Zornow, M.H.; Strnat, M.A. Effect of S-emopamil, nimodipine, and mild hypothermia on hippocampal glutamate concentrations after repeated cerebral ischemia in rabbits. Stroke,  1993, 24(8), 1228-1234.
[http://dx.doi.org/10.1161/01.STR.24.8.1228] [PMID:  8102022] 
[115] 
Busto, R.; Dietrich, W.D.; Globus, M.Y.; Valdés, I.; Scheinberg, P.; Ginsberg, M.D. Small differences in intraischemic brain temperature critically determine the extent of ischemic neuronal injury. J. Cereb. Blood Flow Metab.,  1987, 7(6), 729-738.
[http://dx.doi.org/10.1038/jcbfm.1987.127] [PMID:  3693428] 
[116] 
Colbourne, F.; Grooms, S.Y.; Zukin, R.S.; Buchan, A.M.; Bennett, M.V. Hypothermia rescues hippocampal CA1 neurons and attenuates down-regulation of the AMPA receptor GluR2 subunit after forebrain ischemia. Proc. Natl. Acad. Sci. USA,  2003, 100(5), 2906-2910.
[http://dx.doi.org/10.1073/pnas.2628027100] [PMID:  12606709] 
[117] 
Kim, J.Y.; Kim, N.; Yenari, M.A.; Chang, W. Mild hypothermia suppresses calcium-sensing receptor (casr) induction following forebrain ischemia while increasing gaba-b receptor 1 (gaba-b-r1) expression. Transl. Stroke Res.,  2011, 2(2), 195-201.
[http://dx.doi.org/10.1007/s12975-011-0082-4] [PMID:  21731589] 
[118] 
Ginsberg, M.D.; Sternau, L.L.; Globus, M.Y.; Dietrich, W.D.; Busto, R. Therapeutic modulation of brain temperature: relevance to ischemic brain injury. Cerebrovasc. Brain Metab. Rev.,  1992, 4(3), 189-225.
[PMID:  1389956] 
[119] 
Kamme, F.; Campbell, K.; Wieloch, T. Biphasic expression of the fos and jun families of transcription factors following transient forebrain ischaemia in the rat. Effect of hypothermia. Eur. J. Neurosci.,  1995, 7(10), 2007-2016.
[http://dx.doi.org/10.1111/j.1460-9568.1995.tb00623.x] [PMID:  8542058] 
[120] 
Yenari, M.A.; Liu, J.; Zheng, Z.; Vexler, Z.S.; Lee, J.E.; Giffard, R.G. Antiapoptotic and anti-inflammatory mechanisms of heat-shock protein protection. Ann. N. Y. Acad. Sci.,  2005, 1053, 74-83.
[http://dx.doi.org/10.1196/annals.1344.007] [PMID:  16179510] 
[121] 
Terao, Y.; Miyamoto, S.; Hirai, K.; Kamiguchi, H.; Ohta, H.; Shimojo, M.; Kiyota, Y.; Asahi, S.; Sakura, Y.; Shintani, Y. Hypothermia enhances heat-shock protein 70 production in ischemic brains. Neuroreport,  2009, 20(8), 745-749.
[http://dx.doi.org/10.1097/WNR.0b013e32832a2f32] [PMID:  19352207] 
[122] 
Truettner, J.S.; Alonso, O.F.; Bramlett, H.M.; Dietrich, W.D. Therapeutic hypothermia alters microRNA responses to traumatic brain injury in rats. J. Cereb. Blood Flow Metab.,  2011, 31(9), 1897-1907.
[http://dx.doi.org/10.1038/jcbfm.2011.33] [PMID:  21505482] 
[123] 
Tang, X.N.; Yenari, M.A. Hypothermia as a cytoprotective strategy in ischemic tissue injury. Ageing Res. Rev.,  2010, 9(1), 61-68.
[http://dx.doi.org/10.1016/j.arr.2009.10.002] [PMID:  19833233] 
[124] 
Holcik, M.; Lefebvre, C.; Yeh, C.; Chow, T.; Korneluk, R.G. A new internal-ribosome-entry-site motif potentiates XIAP-mediated cytoprotection. Nat. Cell Biol.,  1999, 1(3), 190-192.
[http://dx.doi.org/10.1038/11109] [PMID:  10559907] 
[125] 
Liu, A.; Zhang, Z.; Li, A.; Xue, J. Effects of hypothermia and cerebral ischemia on cold-inducible RNA-binding protein mRNA expression in rat brain. Brain Res.,  2010, 1347, 104-110.
[http://dx.doi.org/10.1016/j.brainres.2010.05.029] [PMID:  20546708] 
[126] 
Chip, S.; Zelmer, A.; Ogunshola, O.O.; Felderhoff-Mueser, U.; Nitsch, C.; Bührer, C.; Wellmann, S. The RNA-binding protein RBM3 is involved in hypothermia induced neuroprotection. Neurobiol. Dis.,  2011, 43(2), 388-396.
[http://dx.doi.org/10.1016/j.nbd.2011.04.010] [PMID:  21527344] 
[127] 
Green, D.R.; Reed, J.C. Mitochondria and apoptosis. Science,  1998, 281(5381), 1309-1312.
[http://dx.doi.org/10.1126/science.281.5381.1309] [PMID:  9721092] 
[128] 
Ashkenazi, A.; Dixit, V.M. Death receptors: signaling and modulation. Science,  1998, 281(5381), 1305-1308.
[http://dx.doi.org/10.1126/science.281.5381.1305] [PMID:  9721089] 
[129] 
Prakasa Babu, P.; Yoshida, Y.; Su, M.; Segura, M.; Kawamura, S.; Yasui, N. Immunohistochemical expression of Bcl-2, Bax and cytochrome c following focal cerebral ischemia and effect of hypothermia in rat. Neurosci. Lett.,  2000, 291(3), 196-200.
[http://dx.doi.org/10.1016/S0304-3940(00)01404-X] [PMID:  10984640] 
[130] 
Slikker, W., III; Desai, V.G.; Duhart, H.; Feuers, R.; Imam, S.Z. Hypothermia enhances bcl-2 expression and protects against oxidative stress-induced cell death in Chinese hamster ovary cells. Free Radic. Biol. Med.,  2001, 31(3), 405-411.
[http://dx.doi.org/10.1016/S0891-5849(01)00593-7] [PMID:  11461779] 
[131] 
Zhang, Z.; Sobel, R.A.; Cheng, D.; Steinberg, G.K.; Yenari, M.A. Mild hypothermia increases Bcl-2 protein expression following global cerebral ischemia. Brain Res. Mol. Brain Res.,  2001, 95(1-2), 75-85.
[http://dx.doi.org/10.1016/S0169-328X(01)00247-9] [PMID:  11687278] 
[132] 
Inamasu, J.; Suga, S.; Sato, S.; Horiguchi, T.; Akaji, K.; Mayanagi, K.; Kawase, T. Postischemic hypothermia attenuates apoptotic cell death in transient focal ischemia in rats. Acta Neurochir. Suppl.,  2000, 76, 525-527.
[http://dx.doi.org/10.1007/978-3-7091-6346-7_110] [PMID: 11450083] 
[133] 
Yenari, M.A.; Iwayama, S.; Cheng, D.; Sun, G.H.; Fujimura, M.; Morita-Fujimura, Y.; Chan, P.H.; Steinberg, G.K. Mild hypothermia attenuates cytochrome c release but does not alter Bcl-2 expression or caspase activation after experimental stroke. J. Cereb. Blood Flow Metab.,  2002, 22(1), 29-38.
[http://dx.doi.org/10.1097/00004647-200201000-00004] [PMID:  11807391] 
[134] 
Phanithi, P.B.; Yoshida, Y.; Santana, A.; Su, M.; Kawamura, S.; Yasui, N. Mild hypothermia mitigates post-ischemic neuronal death following focal cerebral ischemia in rat brain: immunohistochemical study of Fas, caspase-3 and TUNEL. Neuropathology,  2000, 20(4), 273-282.
[PMID:  11211051] 
[135] 
Xu, L.; Yenari, M.A.; Steinberg, G.K.; Giffard, R.G. Mild hypothermia reduces apoptosis of mouse neurons in vitro early in the cascade. J. Cereb. Blood Flow Metab.,  2002, 22(1), 21-28.
[http://dx.doi.org/10.1097/00004647-200201000-00003] [PMID:  11807390] 
[136] 
Bright, R.; Raval, A.P.; Dembner, J.M.; Pérez-Pinzón, M.A.; Steinberg, G.K.; Yenari, M.A.; Mochly-Rosen, D. Protein kinase C delta mediates cerebral reperfusion injury in vivo. J. Neurosci.,  2004, 24(31), 6880-6888.
[http://dx.doi.org/10.1523/JNEUROSCI.4474-03.2004] [PMID:  15295022] 
[137] 
Raval, A.P.; Dave, K.R.; Prado, R.; Katz, L.M.; Busto, R.; Sick, T.J.; Ginsberg, M.D.; Mochly-Rosen, D.; Pérez-Pinzón, M.A. Protein kinase C delta cleavage initiates an aberrant signal transduction pathway after cardiac arrest and oxygen glucose deprivation. J. Cereb. Blood Flow Metab.,  2005, 25(6), 730-741.
[http://dx.doi.org/10.1038/sj.jcbfm.9600071] [PMID:  15716854] 
[138] 
Lee, S.M.; Zhao, H.; Maier, C.M.; Steinberg, G.K. The protective effect of early hypothermia on PTEN phosphorylation correlates with free radical inhibition in rat stroke. J. Cereb. Blood Flow Metab.,  2009, 29(9), 1589-1600.
[http://dx.doi.org/10.1038/jcbfm.2009.81] [PMID:  19553907] 
[139] 
Shimohata, T.; Zhao, H.; Steinberg, G.K. Epsilon PKC may contribute to the protective effect of hypothermia in a rat focal cerebral ischemia model. Stroke,  2007, 38(2), 375-380.
[http://dx.doi.org/10.1161/01.STR.0000254616.78387.ee] [PMID:  17204679] 
[140] 
Hamann, G.F.; Burggraf, D.; Martens, H.K.; Liebetrau, M.; Jäger, G.; Wunderlich, N.; DeGeorgia, M.; Krieger, D.W. Mild to moderate hypothermia prevents microvascular basal lamina antigen loss in experimental focal cerebral ischemia. Stroke,  2004, 35(3), 764-769.
[http://dx.doi.org/10.1161/01.STR.0000116866.60794.21] [PMID:  14976330] 
[141] 
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] 
[142] 
Liu, L.; Kim, J.Y.; Koike, M.A.; Yoon, Y.J.; Tang, X.N.; Ma, H.; Lee, H.; Steinberg, G.K.; Lee, J.E.; Yenari, M.A. FasL shedding is reduced by hypothermia in experimental stroke. J. Neurochem.,  2008, 106(2), 541-550.
[http://dx.doi.org/10.1111/j.1471-4159.2008.05411.x] [PMID:  18410517] 
[143] 
Kim, J.Y.; Kim, N.; Lee, J.E.; Yenari, M.A. Hypothermia identifies dynamin as a potential therapeutic target in experimental stroke. Ther. Hypothermia Temp. Manag.,  2017, 7(3), 171-177.
[http://dx.doi.org/10.1089/ther.2017.0005] [PMID:  28665255] 
[144] 
Susin, S.A.; Lorenzo, H.K.; Zamzami, N.; Marzo, I.; Snow, B.E.; Brothers, G.M.; Mangion, J.; Jacotot, E.; Costantini, P.; Loeffler, M.; Larochette, N.; Goodlett, D.R.; Aebersold, R.; Siderovski, D.P.; Penninger, J.M.; Kroemer, G. Molecular characterization of mitochondrial apoptosis-inducing factor. Nature,  1999, 397(6718), 441-446.
[http://dx.doi.org/10.1038/17135] [PMID:  9989411] 
[145] 
Zhao, H.; Wang, J.Q.; Shimohata, T.; Sun, G.; Yenari, M.A.; Sapolsky, R.M.; Steinberg, G.K. Conditions of protection by hypothermia and effects on apoptotic pathways in a rat model of permanent middle cerebral artery occlusion. J. Neurosurg.,  2007, 107(3), 636-641.
[http://dx.doi.org/10.3171/JNS-07/09/0636] [PMID:  17886565] 
[146] 
Shi, G.D.; OuYang, Y.P.; Shi, J.G.; Liu, Y.; Yuan, W.; Jia, L.S. PTEN deletion prevents ischemic brain injury by activating the mTOR signaling pathway. Biochem. Biophys. Res. Commun.,  2011, 404(4), 941-945.
[http://dx.doi.org/10.1016/j.bbrc.2010.12.085] [PMID:  21185267] 
[147] 
Zhao, H.; Steinberg, G.K.; Sapolsky, R.M. General versus specific actions of mild-moderate hypothermia in attenuating cerebral ischemic damage. J. Cereb. Blood Flow Metab.,  2007, 27(12), 1879-1894.
[http://dx.doi.org/10.1038/sj.jcbfm.9600540] [PMID:  17684517] 
[148] 
Vosler, P.S.; Logue, E.S.; Repine, M.J.; Callaway, C.W. Delayed hypothermia preferentially increases expression of brain-derived neurotrophic factor exon III in rat hippocampus after asphyxial cardiac arrest. Brain Res. Mol. Brain Res.,  2005, 135(1-2), 21-29.
[http://dx.doi.org/10.1016/j.molbrainres.2004.11.006] [PMID:  15857665] 
[149] 
D’Cruz, B.J.; Fertig, K.C.; Filiano, A.J.; Hicks, S.D.; DeFranco, D.B.; Callaway, C.W. Hypothermic reperfusion after cardiac arrest augments brain-derived neurotrophic factor activation. J. Cereb. Blood Flow Metab.,  2002, 22(7), 843-851.
[http://dx.doi.org/10.1097/00004647-200207000-00009] [PMID:  12142569] 
[150] 
Schmidt, K.M.; Repine, M.J.; Hicks, S.D.; DeFranco, D.B.; Callaway, C.W. Regional changes in glial cell line-derived neurotrophic factor after cardiac arrest and hypothermia in rats. Neurosci. Lett.,  2004, 368(2), 135-139.
[http://dx.doi.org/10.1016/j.neulet.2004.06.071] [PMID:  15351435] 
[151] 
Boris-Möller, F.; Kamme, F.; Wieloch, T. The effect of hypothermia on the expression of neurotrophin mRNA in the hippocampus following transient cerebral ischemia in the rat. Brain Res. Mol. Brain Res.,  1998, 63(1), 163-173.
[http://dx.doi.org/10.1016/S0169-328X(98)00286-1] [PMID:  9838092] 
[152] 
Schmitt, K.R.; Diestel, A.; Lehnardt, S.; Schwartlander, R.; Lange, P.E.; Berger, F.; Ullrich, O.; Abdul-Khaliq, H. Hypothermia suppresses inflammation via ERK signaling pathway in stimulated microglial cells. J. Neuroimmunol.,  2007, 189(1-2), 7-16.
[http://dx.doi.org/10.1016/j.jneuroim.2007.06.010] [PMID:  17651818] 
[153] 
Zhao, H.; Shimohata, T.; Wang, J.Q.; Sun, G.; Schaal, D.W.; Sapolsky, R.M.; Steinberg, G.K. Akt contributes to neuroprotection by hypothermia against cerebral ischemia in rats. J. Neurosci.,  2005, 25(42), 9794-9806.
[http://dx.doi.org/10.1523/JNEUROSCI.3163-05.2005] [PMID:  16237183] 
[154] 
Mehta, S.L.; Manhas, N.; Raghubir, R. Molecular targets in cerebral ischemia for developing novel therapeutics. Brain Res. Brain Res. Rev.,  2007, 54(1), 34-66.
[http://dx.doi.org/10.1016/j.brainresrev.2006.11.003] [PMID:  17222914] 
[155] 
Kim, J.Y.; Kawabori, M.; Yenari, M.A. Innate inflammatory responses in stroke: mechanisms and potential therapeutic targets. Curr. Med. Chem.,  2014, 21(18), 2076-2097.
[http://dx.doi.org/10.2174/0929867321666131228205146] [PMID:  24372209] 
[156] 
Wang, Q.; Tang, X.N.; Yenari, M.A. The inflammatory response in stroke. J. Neuroimmunol.,  2007, 184(1-2), 53-68.
[http://dx.doi.org/10.1016/j.jneuroim.2006.11.014] [PMID:  17188755] 
[157] 
Ceulemans, A.G.; Zgavc, T.; Kooijman, R.; Hachimi-Idrissi, S.; Sarre, S.; Michotte, Y. The dual role of the neuroinflammatory response after ischemic stroke: modulatory effects of hypothermia. J. Neuroinflammation,  2010, 7, 74.
[http://dx.doi.org/10.1186/1742-2094-7-74] [PMID:  21040547] 
[158] 
Rivest, S. Regulation of innate immune responses in the brain. Nat. Rev. Immunol.,  2009, 9(6), 429-439.
[http://dx.doi.org/10.1038/nri2565] [PMID:  19461673] 
[159] 
Zheng, Z.; Yenari, M.A. Post-ischemic inflammation: molecular mechanisms and therapeutic implications. Neurol. Res.,  2004, 26(8), 884-892.
[http://dx.doi.org/10.1179/016164104X2357] [PMID:  15727272] 
[160] 
Ransohoff, R.M. Immunology: Barrier to electrical storms. Nature,  2009, 457(7226), 155-156.
[http://dx.doi.org/10.1038/457155a] [PMID:  19129836] 
[161] 
Van Hemelrijck, A.; Vermijlen, D.; Hachimi-Idrissi, S.; Sarre, S.; Ebinger, G.; Michotte, Y. Effect of resuscitative mild hypothermia on glutamate and dopamine release, apoptosis and ischaemic brain damage in the endothelin-1 rat model for focal cerebral ischaemia. J. Neurochem.,  2003, 87(1), 66-75.
[http://dx.doi.org/10.1046/j.1471-4159.2003.01977.x] [PMID:  12969253] 
[162] 
Patel, A.R.; Ritzel, R.; McCullough, L.D.; Liu, F. Microglia and ischemic stroke: a double-edged sword. Int. J. Physiol. Pathophysiol. Pharmacol.,  2013, 5(2), 73-90.
[PMID:  23750306] 
[163] 
Ghosh, S.; May, M.J.; Kopp, E.B. NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu. Rev. Immunol.,  1998, 16, 225-260.
[http://dx.doi.org/10.1146/annurev.immunol.16.1.225] [PMID:  9597130] 
[164] 
Yilmaz, G.; Granger, D.N. Cell adhesion molecules and ischemic stroke. Neurol. Res.,  2008, 30(8), 783-793.
[http://dx.doi.org/10.1179/174313208X341085] [PMID:  18826804] 
[165] 
Yenari, M.A.; Han, H.S. Influence of hypothermia on post-ischemic inflammation: role of nuclear factor kappa B (NFkappaB). Neurochem. Int.,  2006, 49(2), 164-169.
[http://dx.doi.org/10.1016/j.neuint.2006.03.016] [PMID:  16750872] 
[166] 
Choi, J.S.; Park, J.; Suk, K.; Moon, C.; Park, Y.K.; Han, H.S. Mild hypothermia attenuates intercellular adhesion molecule-1 induction via activation of extracellular signal-regulated kinase-1/2 in a focal cerebral ischemia model. Stroke Res. Treat.,  2011, 2011846716
[http://dx.doi.org/10.4061/2011/846716] [PMID:  21716663] 
[167] 
Tong, G.; Krauss, A.; Mochner, J.; Wollersheim, S.; Soltani, P.; Berger, F.; Schmitt, K.R.L. Deep hypothermia therapy attenuates LPS-induced microglia neuroinflammation via the STAT3 pathway. Neuroscience,  2017, 358, 201-210.
[http://dx.doi.org/10.1016/j.neuroscience.2017.06.055] [PMID:  28687308] 
[168] 
Trendelenburg, G. Acute neurodegeneration and the inflammasome: central processor for danger signals and the inflammatory response? J. Cereb. Blood Flow Metab.,  2008, 28(5), 867-881.
[http://dx.doi.org/10.1038/sj.jcbfm.9600609] [PMID:  18212795] 
[169] 
Matsui, T.; Kakeda, T. IL-10 production is reduced by hypothermia but augmented by hyperthermia in rat microglia. J. Neurotrauma,  2008, 25(6), 709-715.
[http://dx.doi.org/10.1089/neu.2007.0482] [PMID:  18533891] 
[170] 
Sugawara, T.; Chan, P.H. Reactive oxygen radicals and pathogenesis of neuronal death after cerebral ischemia. Antioxid. Redox Signal.,  2003, 5(5), 597-607.
[http://dx.doi.org/10.1089/152308603770310266] [PMID:  14580316] 
[171] 
Wong, C.H.; Crack, P.J. Modulation of neuro-inflammation and vascular response by oxidative stress following cerebral ischemia-reperfusion injury. Curr. Med. Chem.,  2008, 15(1), 1-14.
[http://dx.doi.org/10.2174/092986708783330665] [PMID:  18220759] 
[172] 
Globus, M.Y.; Busto, R.; Lin, B.; Schnippering, H.; Ginsberg, M.D. Detection of free radical activity during transient global ischemia and recirculation: effects of intraischemic brain temperature modulation. J. Neurochem.,  1995, 65(3), 1250-1256.
[http://dx.doi.org/10.1046/j.1471-4159.1995.65031250.x] [PMID:  7643104] 
[173] 
Maier, C.M.; Sun, G.H.; Cheng, D.; Yenari, M.A.; Chan, P.H.; Steinberg, G.K. Effects of mild hypothermia on superoxide anion production, superoxide dismutase expression, and activity following transient focal cerebral ischemia. Neurobiol. Dis.,  2002, 11(1), 28-42.
[http://dx.doi.org/10.1006/nbdi.2002.0513] [PMID:  12460544] 
[174] 
Liu, L.; Yenari, M.A. Therapeutic hypothermia: neuroprotective mechanisms. Front. Biosci.,  2006, 12, 816-825.
[http://dx.doi.org/10.2741/2104] [PMID:  17127332] 
[175] 
Moro, M.A.; Cárdenas, A.; Hurtado, O.; Leza, J.C.; Lizasoain, I. Role of nitric oxide after brain ischaemia. Cell Calcium,  2004, 36(3-4), 265-275.
[http://dx.doi.org/10.1016/j.ceca.2004.02.011] [PMID:  15261482] 
[176] 
Deng, H.; Han, H.S.; Cheng, D.; Sun, G.H.; Yenari, M.A. Mild hypothermia inhibits inflammation after experimental stroke and brain inflammation. Stroke,  2003, 34(10), 2495-2501.
[http://dx.doi.org/10.1161/01.STR.0000091269.67384.E7] [PMID:  12970518] 
[177] 
Dietrich, W.D.; Busto, R.; Halley, M.; Valdes, I. The importance of brain temperature in alterations of the blood-brain barrier following cerebral ischemia. J. Neuropathol. Exp. Neurol.,  1990, 49(5), 486-497.
[http://dx.doi.org/10.1097/00005072-199009000-00004] [PMID:  2273405] 
[178] 
Kawanishi, M.; Kawai, N.; Nakamura, T.; Luo, C.; Tamiya, T.; Nagao, S. Effect of delayed mild brain hypothermia on edema formation after intracerebral hemorrhage in rats. J. Stroke Cerebrovasc. Dis.,  2008, 17(4), 187-195.
[http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2008.01.003] [PMID:  18589338] 
[179] 
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] 
[180] 
Montaner, J.; Alvarez-Sabín, J.; Molina, C.; Anglés, A.; Abilleira, S.; Arenillas, J.; González, M.A.; Monasterio, J. Matrix metalloproteinase expression after human cardioembolic stroke: temporal profile and relation to neurological impairment. Stroke,  2001, 32(8), 1759-1766.
[http://dx.doi.org/10.1161/01.STR.32.8.1759] [PMID:  11486102] 
[181] 
Gidday, J.M.; Gasche, Y.G.; Copin, J.C.; Shah, A.R.; Perez, R.S.; Shapiro, S.D.; Chan, P.H.; Park, T.S. Leukocyte-derived matrix metalloproteinase-9 mediates blood-brain barrier breakdown and is proinflammatory after transient focal cerebral ischemia. Am. J. Physiol. Heart Circ. Physiol.,  2005, 289(2), H558-H568.
[http://dx.doi.org/10.1152/ajpheart.01275.2004] [PMID:  15764676] 
[182] 
Kurisu, K.; Abumiya, T.; Nakamura, H.; Shimbo, D.; Shichinohe, H.; Nakayama, N.; Kazumata, K.; Shimizu, H.; Houkin, K. Transarterial regional brain hypothermia inhibits acute aquaporin-4 surge and sequential microvascular events in ischemia/reperfusion injury. Neurosurgery,  2016, 79(1), 125-134.
[http://dx.doi.org/10.1227/NEU.0000000000001088] [PMID:  26516820] 
[183] 
Manley, G.T.; Fujimura, M.; Ma, T.; Noshita, N.; Filiz, F.; Bollen, A.W.; Chan, P.; Verkman, A.S. Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke. Nat. Med.,  2000, 6(2), 159-163.
[http://dx.doi.org/10.1038/72256] [PMID:  10655103] 
[184] 
Xiao, F.; Arnold, T.C.; Zhang, S.; Brown, C.; Alexander, J.S.; Carden, D.L.; Conrad, S.A. Cerebral cortical aquaporin-4 expression in brain edema following cardiac arrest in rats. Academic emergency medicine : official journal of the Society
for Academic Emergency Medicine,  2004, 11, 1001-1007.
[http://dx.doi.org/10.1197/j.aem.2004.05.026] 
[185] 
Kernie, S.G.; Parent, J.M. Forebrain neurogenesis after focal Ischemic and traumatic brain injury. Neurobiol. Dis.,  2010, 37(2), 267-274.
[http://dx.doi.org/10.1016/j.nbd.2009.11.002] [PMID:  19909815] 
[186] 
Font, M.A.; Arboix, A.; Krupinski, J. Angiogenesis, neurogenesis and neuroplasticity in ischemic stroke. Curr. Cardiol. Rev.,  2010, 6(3), 238-244.
[http://dx.doi.org/10.2174/157340310791658802] [PMID:  21804783] 
[187] 
Shruster, A.; Melamed, E.; Offen, D. Neurogenesis in the aged and neurodegenerative brain. Apoptosis,  2010, 15(11), 1415-1421.
[http://dx.doi.org/10.1007/s10495-010-0491-y] [PMID:  20339917] 
[188] 
Saito, K.; Fukuda, N.; Matsumoto, T.; Iribe, Y.; Tsunemi, A.; Kazama, T.; Yoshida-Noro, C.; Hayashi, N. Moderate low temperature preserves the stemness of neural stem cells and suppresses apoptosis of the cells via activation of the cold-inducible RNA binding protein. Brain Res.,  2010, 1358, 20-29.
[http://dx.doi.org/10.1016/j.brainres.2010.08.048] [PMID:  20735994] 
[189] 
Kanagawa, T.; Fukuda, H.; Tsubouchi, H.; Komoto, Y.; Hayashi, S.; Fukui, O.; Shimoya, K.; Murata, Y. A decrease of cell proliferation by hypothermia in the hippocampus of the neonatal rat. Brain Res.,  2006, 1111(1), 36-40.
[http://dx.doi.org/10.1016/j.brainres.2006.06.112] [PMID:  16904084] 
[190] 
Xiong, M.; Cheng, G.Q.; Ma, S.M.; Yang, Y.; Shao, X.M.; Zhou, W.H. Post-ischemic hypothermia promotes generation of neural cells and reduces apoptosis by Bcl-2 in the striatum of neonatal rat brain. Neurochem. Int.,  2011, 58(6), 625-633.
[http://dx.doi.org/10.1016/j.neuint.2011.01.026] [PMID:  21300124] 
[191] 
Silasi, G.; Colbourne, F. Therapeutic hypothermia influences cell genesis and survival in the rat hippocampus following global ischemia. J. Cereb. Blood Flow Metab.,  2011, 31(8), 1725-1735.
[http://dx.doi.org/10.1038/jcbfm.2011.25] [PMID:  21364603] 
[192] 
Lasarzik, I.; Winkelheide, U.; Thal, S.C.; Benz, N.; Lörscher, M.; Jahn-Eimermacher, A.; Werner, C.; Engelhard, K. Mild hypothermia has no long-term impact on postischemic neurogenesis in rats. Anesth. Analg.,  2009, 109(5), 1632-1639.
[http://dx.doi.org/10.1213/ANE.0b013e3181bab451] [PMID:  19843801] 
[193] 
Bennet, L.; Roelfsema, V.; George, S.; Dean, J.M.; Emerald, B.S.; Gunn, A.J. The effect of cerebral hypothermia on white and grey matter injury induced by severe hypoxia in preterm fetal sheep. J. Physiol.,  2007, 578(Pt 2), 491-506.
[http://dx.doi.org/10.1113/jphysiol.2006.119602] [PMID:  17095565] 
[194] 
Matijasevic, Z.; Snyder, J.E.; Ludlum, D.B. Hypothermia causes a reversible, p53-mediated cell cycle arrest in cultured fibroblasts. Oncol. Res.,  1998, 10(11-12), 605-610.
[PMID:  10367942] 
[195] 
Gopurappilly, R.; Pal, R.; Mamidi, M.K.; Dey, S.; Bhonde, R.; Das, A.K. Stem cells in stroke repair: current success and future prospects. CNS Neurol. Disord. Drug Targets,  2011, 10(6), 741-756.
[http://dx.doi.org/10.2174/187152711797247894] [PMID:  21838668] 
[196] 
Li, L.; Harms, K.M.; Ventura, P.B.; Lagace, D.C.; Eisch, A.J.; Cunningham, L.A. Focal cerebral ischemia induces a multilineage cytogenic response from adult subventricular zone that is predominantly gliogenic. Glia,  2010, 58(13), 1610-1619.
[http://dx.doi.org/10.1002/glia.21033] [PMID:  20578055] 
[197] 
Hawthorne, A.L.; Hu, H.; Kundu, B.; Steinmetz, M.P.; Wylie, C.J.; Deneris, E.S.; Silver, J. The unusual response of serotonergic neurons after CNS Injury: lack of axonal dieback and enhanced sprouting within the inhibitory environment of the glial scar. J. Neurosci.,  2011, 31(15), 5605-5616.
[http://dx.doi.org/10.1523/JNEUROSCI.6663-10.2011] [PMID:  21490201] 
[198] 
Trendelenburg, G.; Dirnagl, U. Neuroprotective role of astrocytes in cerebral ischemia: focus on ischemic preconditioning. Glia,  2005, 50(4), 307-320.
[http://dx.doi.org/10.1002/glia.20204] [PMID:  15846804] 
[199] 
Xie, Y.C.; Li, C.Y.; Li, T.; Nie, D.Y.; Ye, F. Effect of mild hypothermia on angiogenesis in rats with focal cerebral ischemia. Neurosci. Lett.,  2007, 422(2), 87-90.
[http://dx.doi.org/10.1016/j.neulet.2007.03.072] [PMID:  17630209] 
[200] 
Kao, C.H.; Chio, C.C.; Lin, M.T.; Yeh, C.H. Body cooling ameliorating spinal cord injury may be neurogenesis-, anti-inflammation- and angiogenesis-associated in rats. J. Trauma,  2011, 70(4), 885-893.
[http://dx.doi.org/10.1097/TA.0b013e3181e7456d] [PMID:  20693909] 
[201] 
Kuo, J.R.; Lo, C.J.; Chang, C.P.; Lin, H.J.; Lin, M.T.; Chio, C.C. Brain cooling-stimulated angiogenesis and neurogenesis attenuated traumatic brain injury in rats. J. Trauma,  2010, 69(6), 1467-1472.
[http://dx.doi.org/10.1097/TA.0b013e3181f31b06] [PMID:  21150525] 
[202] 
Lotocki, G.; de Rivero Vaccari, J.; Alonso, O.; Molano, J.S.; Nixon, R.; Dietrich, W.D.; Bramlett, H.M. Oligodendrocyte vulnerability following traumatic brain injury in rats: Effect of moderate hypothermia. Ther. Hypothermia Temp. Manag.,  2011, 1(1), 43-51.
[http://dx.doi.org/10.1089/ther.2010.0011] [PMID:  23336085] 
[203] 
Imada, S.; Yamamoto, M.; Tanaka, K.; Seiwa, C.; Watanabe, K.; Kamei, Y.; Kozuma, S.; Taketani, Y.; Asou, H. Hypothermia-induced increase of oligodendrocyte precursor cells: Possible involvement of plasmalemmal voltage-dependent anion channel 1. J. Neurosci. Res.,  2010, 88(16), 3457-3466.
[http://dx.doi.org/10.1002/jnr.22520] [PMID:  20936704] 
[204] 
Schmitt, K.R.; Boato, F.; Diestel, A.; Hechler, D.; Kruglov, A.; Berger, F.; Hendrix, S. Hypothermia-induced neurite outgrowth is mediated by tumor necrosis factor-alpha. Brain Pathol.,  2010, 20(4), 771-779.
[http://dx.doi.org/10.1111/j.1750-3639.2009.00358.x] [PMID:  20070303] 
[205] 
Wang, X.; Zhu, S.; Drozda, M.; Zhang, W.; Stavrovskaya, I.G.; Cattaneo, E.; Ferrante, R.J.; Kristal, B.S.; Friedlander, R.M. Minocycline inhibits caspase-independent and -dependent mitochondrial cell death pathways in models of Huntington’s disease. Proc. Natl. Acad. Sci. USA,  2003, 100(18), 10483-10487.
[http://dx.doi.org/10.1073/pnas.1832501100] [PMID:  12930891] 
[206] 
Tikka, T.M.; Koistinaho, J.E. Minocycline provides neuroprotection against N-methyl-D-aspartate neurotoxicity by inhibiting microglia. J. Immunol.,  2001, 166(12), 7527-7533.
[http://dx.doi.org/10.4049/jimmunol.166.12.7527] [PMID:  11390507] 
[207] 
Tikka, T.; Fiebich, B.L.; Goldsteins, G.; Keinanen, R.; Koistinaho, J. Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia. J. Neurosci.,  2001, 21(8), 2580-2588.
[http://dx.doi.org/10.1523/JNEUROSCI.21-08-02580.2001] [PMID:  11306611] 
[208] 
Yrjänheikki, J.; Tikka, T.; Keinänen, R.; Goldsteins, G.; Chan, P.H.; Koistinaho, J. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Proc. Natl. Acad. Sci. USA,  1999, 96(23), 13496-13500.
[http://dx.doi.org/10.1073/pnas.96.23.13496] [PMID:  10557349] 
[209] 
Murata, Y.; Rosell, A.; Scannevin, R.H.; Rhodes, K.J.; Wang, X.; Lo, E.H. Extension of the thrombolytic time window with minocycline in experimental stroke. Stroke,  2008, 39(12), 3372-3377.
[http://dx.doi.org/10.1161/STROKEAHA.108.514026] [PMID:  18927459] 
[210] 
Lampl, Y.; Boaz, M.; Gilad, R.; Lorberboym, M.; Dabby, R.; Rapoport, A.; Anca-Hershkowitz, M.; Sadeh, M. Minocycline treatment in acute stroke: an open-label, evaluator-blinded study. Neurology,  2007, 69(14), 1404-1410.
[http://dx.doi.org/10.1212/01.wnl.0000277487.04281.db] [PMID:  17909152] 
[211] 
Fagan, S.C.; Waller, J.L.; Nichols, F.T.; Edwards, D.J.; Pettigrew, L.C.; Clark, W.M.; Hall, C.E.; Switzer, J.A.; Ergul, A.; Hess, D.C. Minocycline to improve neurologic outcome in stroke (MINOS): a dose-finding study. Stroke,  2010, 41(10), 2283-2287.
[http://dx.doi.org/10.1161/STROKEAHA.110.582601] [PMID:  20705929] 
[212] 
Switzer, J.A.; Hess, D.C.; Ergul, A.; Waller, J.L.; Machado, L.S.; Portik-Dobos, V.; Pettigrew, L.C.; Clark, W.M.; Fagan, S.C. Matrix metalloproteinase-9 in an exploratory trial of intravenous minocycline for acute ischemic stroke. Stroke,  2011, 42(9), 2633-2635.
[http://dx.doi.org/10.1161/STROKEAHA.111.618215] [PMID:  21737808] 
[213] 
Blacker, D.J.; Prentice, D.; Alvaro, A.; Bates, T.R. 
Bynevelt, M.; Kelly, A.; Kho, L.K.; Kohler, E.; Hankey, G.J.; Thompson, A.; Major, T. Reducing haemorrhagic transformation after thrombolysis for stroke: a strategy utilising minocycline. Stroke Res. Treat.,  2013, 2013362961
[http://dx.doi.org/10.1155/2013/362961] [PMID:  23691430] 
[214] 
Chang, J.J.; Kim-Tenser, M.; Emanuel, B.A.; Jones, G.M.; Chapple, K.; Alikhani, A.; Sanossian, N.; Mack, W.J.; Tsivgoulis, G.; Alexandrov, A.V.; Pourmotabbed, T. Minocycline and matrix metalloproteinase inhibition in acute intracerebral hemorrhage: a pilot study. Eur. J. Neurol.,  2017, 24(11), 1384-1391.
[http://dx.doi.org/10.1111/ene.13403] [PMID:  28929560] 
[215] 
Kappos, L.; Radue, E.W.; O’Connor, P.; Polman, C.; Hohlfeld, R.; Calabresi, P.; Selmaj, K.; Agoropoulou, C.; Leyk, M.; Zhang-Auberson, L.; Burtin, P.; Group, F.S. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N. Engl. J. Med.,  2010, 362(5), 387-401.
[http://dx.doi.org/10.1056/NEJMoa0909494] [PMID:  20089952] 
[216] 
Brait, V.H.; Tarrasón, G.; Gavaldà, A.; Godessart, N.; Planas, A.M. Selective sphingosine 1-phosphate receptor 1 agonist is protective against ischemia/reperfusion in mice. Stroke,  2016, 47(12), 3053-3056.
[http://dx.doi.org/10.1161/STROKEAHA.116.015371] [PMID:  27827329] 
[217] 
Liu, J.; Zhang, C.; Tao, W.; Liu, M. Systematic review and meta-analysis of the efficacy of sphingosine-1-phosphate (S1P) receptor agonist FTY720 (fingolimod) in animal models of stroke. Int. J. Neurosci.,  2013, 123(3), 163-169.
[http://dx.doi.org/10.3109/00207454.2012.749255] [PMID:  23167788] 
[218] 
Gao, C.; Qian, Y.; Huang, J.; Wang, D.; Su, W.; Wang, P.; Guo, L.; Quan, W.; An, S.; Zhang, J.; Jiang, R. A three-day consecutive fingolimod administration improves neurological functions and modulates multiple immune responses of cci mice. Mol. Neurobiol.,  2017, 54(10), 8348-8360.
[http://dx.doi.org/10.1007/s12035-016-0318-0] [PMID:  27924525] 
[219] 
Zhang, L.; Ding, K.; Wang, H.; Wu, Y.; Xu, J. Traumatic brain injury-induced neuronal apoptosis is reduced through modulation of pi3k and autophagy pathways in mouse by fty720. Cell. Mol. Neurobiol.,  2016, 36(1), 131-142.
[http://dx.doi.org/10.1007/s10571-015-0227-1] [PMID:  26099903] 
[220] 
Campos, F.; Qin, T.; Castillo, J.; Seo, J.H.; Arai, K.; Lo, E.H.; Waeber, C. Fingolimod reduces hemorrhagic transformation associated with delayed tissue plasminogen activator treatment in a mouse thromboembolic model. Stroke,  2013, 44(2), 505-511.
[http://dx.doi.org/10.1161/STROKEAHA.112.679043] [PMID:  23287783] 
[221] 
Massberg, S.; von Andrian, U.H. Fingolimod and sphingosine-1-phosphate--modifiers of lymphocyte migration. N. Engl. J. Med.,  2006, 355(11), 1088-1091.
[http://dx.doi.org/10.1056/NEJMp068159] [PMID:  16971715] 
[222] 
Hasegawa, Y.; Suzuki, H.; Sozen, T.; Rolland, W.; Zhang, J.H. Activation of sphingosine 1-phosphate receptor-1 by FTY720 is neuroprotective after ischemic stroke in rats. Stroke,  2010, 41(2), 368-374.
[http://dx.doi.org/10.1161/STROKEAHA.109.568899] [PMID:  19940275] 
[223] 
Fu, Y.; Zhang, N.; Ren, L.; Yan, Y.; Sun, N.; Li, Y.J.; Han, W.; Xue, R.; Liu, Q.; Hao, J.; Yu, C.; Shi, F.D. Impact of an immune modulator fingolimod on acute ischemic stroke. Proc. Natl. Acad. Sci. USA,  2014, 111(51), 18315-18320.
[http://dx.doi.org/10.1073/pnas.1416166111] [PMID:  25489101] 
[224] 
Zhu, Z.; Fu, Y.; Tian, D.; Sun, N.; Han, W.; Chang, G.; Dong, Y.; Xu, X.; Liu, Q.; Huang, D.; Shi, F.D. Combination of the immune modulator fingolimod with alteplase in acute ischemic stroke: A pilot trial. Circulation,  2015, 132(12), 1104-1112.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.115.016371] [PMID:  26202811] 
[225] 
Kobayashi, M.S.; Asai, S.; Ishikawa, K.; Nishida, Y.; Nagata, T.; Takahashi, Y. Global profiling of influence of intra-ischemic brain temperature on gene expression in rat brain. Brain Res. Brain Res. Rev.,  2008, 58(1), 171-191.
[http://dx.doi.org/10.1016/j.brainresrev.2008.03.001] [PMID:  18440647] 
[226] 
Kelly, S.; Yenari, M.A. Neuroprotection: heat shock proteins. Curr. Med. Res. Opin.,  2002, 18(Suppl. 2), s55-s60.
[http://dx.doi.org/10.1185/030079902125000732] [PMID:  12365831] 
[227] 
Kim, J.Y.; Kim, N.; Zheng, Z.; Lee, J.E.; Yenari, M.A. 70-kda heat shock protein downregulates dynamin in experimental stroke: A new therapeutic target? Stroke,  2016, 47(8), 2103-2111.
[http://dx.doi.org/10.1161/STROKEAHA.116.012763] [PMID:  27387989] 
[228] 
Kim, J.Y.; Kim, N.; Zheng, Z.; Lee, J.E.; Yenari, M.A. The 70 kDa heat shock protein protects against experimental traumatic brain injury. Neurobiol. Dis.,  2013, 58, 289-295.
[http://dx.doi.org/10.1016/j.nbd.2013.06.012] [PMID:  23816752] 
[229] 
Kumar, K.; Wu, X.; Evans, A.T.; Marcoux, F. The effect of hypothermia on induction of heat shock protein (HSP)-72 in ischemic brain. Metab. Brain Dis.,  1995, 10(4), 283-291.
[http://dx.doi.org/10.1007/BF02109359] [PMID:  8847992] 
[230] 
Lee, B.S.; Jung, E.; Lee, Y.; Chung, S.H. Hypothermia decreased the expression of heat shock proteins in neonatal rat model of hypoxic ischemic encephalopathy. Cell Stress Chaperones,  2017, 22(3), 409-415.
[http://dx.doi.org/10.1007/s12192-017-0782-0] [PMID:  28285429] 
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DOI https://dx.doi.org/10.2174/0929867326666190506124836	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
当代药物化学

急性神经系统疾病的治疗性低温治疗和神经保护

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当代药物化学

急性神经系统疾病的治疗性低温治疗和神经保护

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