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Current Neurovascular Research

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ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

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Research Article

miR-666-3p Mediates the Protective Effects of Mesenchymal Stem Cell-derived Exosomes Against Oxygen-glucose Deprivation and Reoxygenation- induced Cell Injury in Brain Microvascular Endothelial Cells via Mitogen-activated Protein Kinase Pathway

Author(s): Li-yun Kong, Yan Li, Ding-yu Rao, Bing Wu, Cheng-peng Sang, Ping Lai, Jun-song Ye, Zu-xiong Zhang, Zhi-ming Du, Jun-jian Yu, Liang Gu, Fa-chun Xie, Zi-you Liu* and Zhi-xian Tang*

Volume 18, Issue 1, 2021

Published on: 19 March, 2021

Page: [20 - 77] Pages: 58

DOI: 10.2174/1567202618666210319152534

Price: $65

Abstract

Background: Previous studies have reported that mesenchymal stem cell (MSC)- derived exosomes can protect primary rat brain microvascular endothelial cells (BMECs) against oxygen-glucose deprivation and reoxygenation (OGD/R)-induced injury.

Objective: The aim was to identify the key factors mediating the protective effects of MSC-derived exosomes.

Methods: Primary rat BMECs were either pretreated or not pretreated with MSC-derived exosomes before exposure to OGD/R. Naïve cells were used as a control. After performing small RNA deep sequencing, quantitative reverse transcription polymerase chain reaction was performed to validate microRNA (miRNA) expression. The effects of rno-miR-666-3p on cell viability, apoptosis, and inflammation in OGD/R-exposed cells were assessed by performing the Cell Counting Kit 8 assay, flow cytometry, and enzyme-linked immunosorbent assay, respectively. Moreover, the role of rno-miR-666-3p in regulating gene expression in OGD/R-exposed cells was studied using mRNA deep sequencing. Lastly, to evaluate whether mitogen-activated protein kinase 1 (MAPK1) was the target of rno-miR-666-3p, western blotting and the dual-luciferase assay were performed.

Results: MSC-derived exosomes altered the miRNA expression patterns in OGD/R-exposed BMECs. In particular, the expression levels of rno-miR-666-3p, rno-miR-92a-2-5p, and rnomiR- 219a-2-3p decreased in OGD/R-exposed cells compared with those in the control; however, MSC-derived exosomes restored the expression levels of these miRNAs under OGD/R conditions. rno-miR-666-3p overexpression enhanced cell viability and alleviated the apoptosis of OGD/R-exposed cells. Moreover, rno-miR-666-3p suppressed OGD/R-induced inflammation. mRNA deep sequencing revealed that rno-miR-666-3p is closely associated with the MAPK signaling pathway. Western blotting and the dual-luciferase assay confirmed that MAPK1 is the target of rnomiR- 666-3p.

Conclusion: MSC-derived exosomes restore rno-miR-666-3p expression in OGD/R-exposed BMECs. Moreover, this specific miRNA exerts protective effects against OGD/R by suppressing the MAPK signaling pathway.

Keywords: Oxygen–glucose deprivation, brain, endothelial cells, mesenchymal stem cells, exosomes, microRNAs.

« Previous Next »
[1]
Ziganshin BA, Elefteriades JA. Deep hypothermic circulatory arrest. Ann Cardiothorac Surg 2013; 2(3): 303-15.
[PMID: 23977599]
[2]
Dumfarth J, Ziganshin BA, Tranquilli M, Elefteriades JA. Cerebral protection in aortic arch surgery: Hypothermia alone suffices. Tex Heart Inst J 2013; 40(5): 564-5.
[PMID: 24391322]
[3]
Erecinska M, Thoresen M, Silver IA. Effects of hypothermia on energy metabolism in Mammalian central nervous system. J Cereb Blood Flow Metab 2003; 23(5): 513-30.
[http://dx.doi.org/10.1097/01.WCB.0000066287.21705.21] [PMID: 12771566]
[4]
Alva N, Palomeque J, Carbonell T. Oxidative stress and antioxidant activity in hypothermia and rewarming: Can RONS modulate the beneficial effects of therapeutic hypothermia? Oxid Med Cell Longev 2013; 2013: 957054.
[http://dx.doi.org/10.1155/2013/957054] [PMID: 24363826]
[5]
Ma H, Sinha B, Pandya RS, et al. Therapeutic hypothermia as a neuroprotective strategy in neonatal hypoxic-ischemic brain injury and traumatic brain injury. Curr Mol Med 2012; 12(10): 1282-96.
[http://dx.doi.org/10.2174/156652412803833517] [PMID: 22834830]
[6]
Gatti G, Benussi B, Currò P, et al. The risk of neurological dysfunctions after deep hypothermic circulatory arrest with retrograde cerebral perfusion. J Stroke Cerebrovasc Dis 2017; 26(12): 3009-19.
[http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2017.07.034] [PMID: 28844545]
[7]
Krähenbühl ES, Immer FF, Stalder M, Englberger L, Eckstein FS, Carrel TP. Temporary neurological dysfunction after surgery of the thoracic aorta: A predictor of poor outcome and impaired quality of life. Eur J Cardiothorac Surg 2008; 33(6): 1025-9.
[http://dx.doi.org/10.1016/j.ejcts.2008.01.058] [PMID: 18343679]
[8]
Hickey PR, Andersen NP. Deep hypothermic circulatory arrest: A review of pathophysiology and clinical experience as a basis for anesthetic management. J Cardiothorac Anesth 1987; 1(2): 137-55.
[http://dx.doi.org/10.1016/0888-6296(87)90010-X] [PMID: 2979087]
[9]
Amir G, Ramamoorthy C, Riemer RK, Reddy VM, Hanley FL. Neonatal brain protection and deep hypothermic circulatory arrest: Pathophysiology of ischemic neuronal injury and protective strategies. Ann Thorac Surg 2005; 80(5): 1955-64.
[http://dx.doi.org/10.1016/j.athoracsur.2004.12.040] [PMID: 16242503]
[10]
Dewhurst AT, Moore SJ, Liban JB. Pharmacological agents as cerebral protectants during deep hypothermic circulatory arrest in adult thoracic aortic surgery. A survey of current practice. Anaesthesia 2002; 57(10): 1016-21.
[http://dx.doi.org/10.1046/j.1365-2044.2002.02787.x] [PMID: 12358961]
[11]
Conolly S, Arrowsmith JE, Klein AA. Deep hypothermic circulatory arrest. Contin Educ Anaesth Crit Care Pain 2010; 10(5): 138-42.
[http://dx.doi.org/10.1093/bjaceaccp/mkq024]
[12]
Wolburg H, Noell S, Mack A, Wolburg-Buchholz K, Fallier-Becker P. Brain endothelial cells and the glio-vascular complex. Cell Tissue Res 2009; 335(1): 75-96.
[http://dx.doi.org/10.1007/s00441-008-0658-9] [PMID: 18633647]
[13]
Engelhardt S, Huang SF, Patkar S, Gassmann M, Ogunshola OO. Differential responses of blood-brain barrier associated cells to hypoxia and ischemia: A comparative study. Fluids Barriers CNS 2015; 12: 4.
[http://dx.doi.org/10.1186/2045-8118-12-4] [PMID: 25879623]
[14]
Stanimirovic D, Satoh K. Inflammatory mediators of cerebral endothelium: A role in ischemic brain inflammation. Brain Pathol 2000; 10(1): 113-26.
[http://dx.doi.org/10.1111/j.1750-3639.2000.tb00248.x] [PMID: 10668901]
[15]
Ludewig P, Winneberger J, Magnus T. The cerebral endothelial cell as a key regulator of inflammatory processes in sterile inflammation. J Neuroimmunol 2019; 326: 38-44.
[http://dx.doi.org/10.1016/j.jneuroim.2018.10.012] [PMID: 30472304]
[16]
Carr KR, Zuckerman SL, Mocco J. Inflammation, cerebral vasospasm, and evolving theories of delayed cerebral ischemia. Neurol Res Int 2013; 2013: 506584.
[http://dx.doi.org/10.1155/2013/506584] [PMID: 24058736]
[17]
Kong LY, Liang MY, Liu JP, et al. Mesenchymal stem cell-derived exosomes rescue oxygen-glucose deprivation-induced injury in endothelial cells. Curr Neurovasc Res 2020; 17(2): 155-63.
[http://dx.doi.org/10.2174/1567202617666200214103950] [PMID: 32056526]
[18]
Liang X, Ding Y, Zhang Y, Tse HF, Lian Q. Paracrine mechanisms of mesenchymal stem cell-based therapy: Current status and perspectives. Cell Transplant 2014; 23(9): 1045-59.
[http://dx.doi.org/10.3727/096368913X667709] [PMID: 23676629]
[19]
Larpthaveesarp A, Pathipati P, Ostrin S, Rajah A, Ferriero D, Gonzalez FF. Enhanced mesenchymal stromal cells or erythropoietin provide long-term functional benefit after neonatal stroke. Stroke 2021; 52(1): 284-93.
[http://dx.doi.org/10.1161/STROKEAHA.120.031191] [PMID: 33349013]
[20]
Sherman LS, Romagano MP, Williams SF, Rameshwar P. Mesenchymal stem cell therapies in brain disease. Semin Cell Dev Biol 2019; 95: 111-9.
[http://dx.doi.org/10.1016/j.semcdb.2019.03.003] [PMID: 30922957]
[21]
Yong KW, Choi JR, Mohammadi M, Mitha AP, Sanati-Nezhad A, Sen A. Mesenchymal stem cell therapy for ischemic tissues. Stem Cells Int 2018; 2018: 8179075.
[http://dx.doi.org/10.1155/2018/8179075] [PMID: 30402112]
[22]
Shafei AE, Ali MA, Ghanem HG, et al. Mesenchymal stem cell therapy: A promising cell-based therapy for treatment of myocardial infarction. J Gene Med 2017; 19(12)
[http://dx.doi.org/10.1002/jgm.2995] [PMID: 29044850]
[23]
Rowart P, Erpicum P, Detry O, et al. Mesenchymal stromal cell therapy in ischemia/reperfusion injury. J Immunol Res 2015; 2015: 602597.
[http://dx.doi.org/10.1155/2015/602597] [PMID: 26258151]
[24]
Phinney DG, Pittenger MF. Concise review: MSC-derived exosomes for cell-free therapy. Stem Cells 2017; 35(4): 851-8.
[http://dx.doi.org/10.1002/stem.2575] [PMID: 28294454]
[25]
Zhao T, Sun F, Liu J, et al. Emerging role of mesenchymal stem cell-derived exosomes in regenerative medicine. Curr Stem Cell Res Ther 2019; 14(6): 482-94.
[http://dx.doi.org/10.2174/1574888X14666190228103230] [PMID: 30819086]
[26]
Mendt M, Rezvani K, Shpall E. Mesenchymal stem cell-derived exosomes for clinical use. Bone Marrow Transplant 2019; 54(Suppl. 2): 789-92.
[http://dx.doi.org/10.1038/s41409-019-0616-z] [PMID: 31431712]
[27]
Pegtel DM, Gould SJ. Exosomes. Annu Rev Biochem 2019; 88(1): 487-514.
[http://dx.doi.org/10.1146/annurev-biochem-013118-111902] [PMID: 31220978]
[28]
John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks DS. Human MicroRNA targets. PLoS Biol 2004; 2(11): e363.
[http://dx.doi.org/10.1371/journal.pbio.0020363] [PMID: 15502875]
[29]
Bartel DP. MicroRNAs: Target recognition and regulatory functions. Cell 2009; 136(2): 215-33.
[http://dx.doi.org/10.1016/j.cell.2009.01.002] [PMID: 19167326]
[30]
Rana S, Malinowska K, Zöller M. Exosomal tumor microRNA modulates premetastatic organ cells. Neoplasia 2013; 15(3): 281-95.
[http://dx.doi.org/10.1593/neo.122010] [PMID: 23479506]
[31]
Beuzelin D, Kaeffer B. Exosomes and miRNA-loaded biomimetic nanovehicles, a focus on their potentials preventing Type-2 diabetes linked to metabolic syndrome. Front Immunol 2018; 9: 2711.
[http://dx.doi.org/10.3389/fimmu.2018.02711] [PMID: 30519245]
[32]
Zhou J, Li X, Wu X, et al. Exosomes released from tumor-associated macrophages transfer mirnas that induce a Treg/Th17 cell imbalance in epithelial ovarian cancer. Cancer Immunol Res 2018; 6(12): 1578-92.
[http://dx.doi.org/10.1158/2326-6066.CIR-17-0479] [PMID: 30396909]
[33]
Cui H, Yang L. Analysis of microRNA expression detected by microarray of the cerebral cortex after hypoxic-ischemic brain injury. J Craniofac Surg 2013; 24(6): 2147-52.
[http://dx.doi.org/10.1097/SCS.0b013e3182a243f3] [PMID: 24220425]
[34]
Zhai C, Qian Q, Tang G, et al. MicroRNA-206 protects against myocardial ischaemia-reperfusion injury in rats by targeting Gadd45beta. Mol Cells 2017; 40(12): 916-24.
[PMID: 29237256]
[35]
Lim KY, Chua JH, Tan JR, et al. MicroRNAs in cerebral ischemia. Transl Stroke Res 2010; 1(4): 287-303.
[http://dx.doi.org/10.1007/s12975-010-0035-3] [PMID: 24323555]
[36]
Lee ST, Chu K, Jung KH, et al. MicroRNAs induced during ischemic preconditioning. Stroke 2010; 41(8): 1646-51.
[http://dx.doi.org/10.1161/STROKEAHA.110.579649] [PMID: 20576953]
[37]
Hu F, Zhang S, Chen X, et al. MiR-219a-2 relieves myocardial ischemia-reperfusion injury by reducing calcium overload and cell apoptosis through HIF1α/ NMDAR pathway. Exp Cell Res 2020; 395(1): 112172.
[http://dx.doi.org/10.1016/j.yexcr.2020.112172] [PMID: 32682013]
[38]
Ma K, Xu H, Zhang J, et al. Insulin-like growth factor-1 enhances neuroprotective effects of neural stem cell exosomes after spinal cord injury via an miR-219a-2-3p/YY1 mechanism. Aging (Albany NY) 2019; 11(24): 12278-94.
[http://dx.doi.org/10.18632/aging.102568] [PMID: 31848325]
[39]
Maqsood M, Kang M, Wu X, Chen J, Teng L, Qiu L. Adult mesenchymal stem cells and their exosomes: Sources, characteristics, and application in regenerative medicine. Life Sci 2020; 256: 118002.
[http://dx.doi.org/10.1016/j.lfs.2020.118002] [PMID: 32585248]
[40]
Wang S, Qu X, Zhao RC. Clinical applications of mesenchymal stem cells. J Hematol Oncol 2012; 5: 19.
[http://dx.doi.org/10.1186/1756-8722-5-19] [PMID: 22546280]
[41]
Spees JL, Lee RH, Gregory CA. Mechanisms of mesenchymal stem/stromal cell function. Stem Cell Res Ther 2016; 7(1): 125.
[http://dx.doi.org/10.1186/s13287-016-0363-7] [PMID: 27581859]
[42]
Lin W, Huang L, Li Y, et al. Mesenchymal stem cells and cancer: Clinical challenges and opportunities. BioMed Res Int 2019; 2019: 2820853.
[http://dx.doi.org/10.1155/2019/2820853] [PMID: 31205939]
[43]
Roorda BD, ter Elst A, Kamps WA, de Bont ES. Bone marrow-derived cells and tumor growth: contribution of bone marrow-derived cells to tumor micro-environments with special focus on mesenchymal stem cells. Crit Rev Oncol Hematol 2009; 69(3): 187-98.
[http://dx.doi.org/10.1016/j.critrevonc.2008.06.004] [PMID: 18675551]
[44]
Galipeau J, Sensébé L. Mesenchymal stromal cells: Clinical challenges and therapeutic opportunities. Cell Stem Cell 2018; 22(6): 824-33.
[http://dx.doi.org/10.1016/j.stem.2018.05.004] [PMID: 29859173]
[45]
Wang Y, Han ZB, Song YP, Han ZC. Safety of mesenchymal stem cells for clinical application. Stem Cells Int 2012; 2012: 652034.
[http://dx.doi.org/10.1155/2012/652034] [PMID: 22685475]
[46]
Leng J, Liu W, Li L, et al. MicroRNA-429/Cxcl1 axis protective against oxygen glucose deprivation/reoxygenation-induced injury in brain microvascular endothelial cells. Dose Response 2020; 18(2): 1559325820913785.
[http://dx.doi.org/10.1177/1559325820913785] [PMID: 32284700]
[47]
Deng W, Fan C, Shen R, Wu Y, Du R, Teng J. Long noncoding MIAT acting as a ceRNA to sponge microRNA-204-5p to participate in cerebral microvascular endothelial cell injury after cerebral ischemia through regulating HMGB1. J Cell Physiol 2020; 235(5): 4571-86.
[http://dx.doi.org/10.1002/jcp.29334] [PMID: 31628679]
[48]
Ye EA, Steinle JJ. MiR-146a attenuates inflammatory pathways mediated by TLR4/NF-kappaB and TNFalpha to protect primary human retinal microvascular endothelial cells grown in high glucose. Mediators Inflamm 2016; 2016: 3958453.
[http://dx.doi.org/10.1155/2016/3958453] [PMID: 26997759]
[49]
Chen G, Goeddel DV. TNF-R1 signaling: A beautiful pathway. Science 2002; 296(5573): 1634-5.
[http://dx.doi.org/10.1126/science.1071924] [PMID: 12040173]
[50]
Cheng Q, Ning D, Chen J, Li X, Chen XP, Jiang L. SIX1 and DACH1 influence the proliferation and apoptosis of hepatocellular carcinoma through regulating p53. Cancer Biol Ther 2018; 19(5): 381-90.
[http://dx.doi.org/10.1080/15384047.2018.1423920] [PMID: 29333942]
[51]
Sun Y, Liu WZ, Liu T, Feng X, Yang N, Zhou HF. Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis. J Recept Signal Transduct Res 2015; 35(6): 600-4.
[http://dx.doi.org/10.3109/10799893.2015.1030412] [PMID: 26096166]
[52]
Rashidi M, Bandala-Sanchez E, Lawlor KE, et al. CD52 inhibits Toll-like receptor activation of NF-κB and triggers apoptosis to suppress inflammation. Cell Death Differ 2018; 25(2): 392-405.
[http://dx.doi.org/10.1038/cdd.2017.173] [PMID: 29244050]
[53]
Kim YK, Shin JS, Nahm MH. NOD-like receptors in infection, immunity, and diseases. Yonsei Med J 2016; 57(1): 5-14.
[http://dx.doi.org/10.3349/ymj.2016.57.1.5] [PMID: 26632377]
[54]
Ernst O, Glucksam-Galnoy Y, Athamna M, et al. The cAMP pathway amplifies early MyD88-dependent and Type I interferon-independent LPS-induced interleukin-10 expression in mouse macrophages. Mediators Inflamm 2019; 2019: 3451461.
[http://dx.doi.org/10.1155/2019/3451461] [PMID: 31148944]
[55]
Patra C, Foster K, Corley JE, Dimri M, Brady MF. Biochemistry, cAMP. Treasure Island, FL: StatPearls Publishing 2020.
[56]
Rajakulendran N, Rowland KJ, Selvadurai HJ, et al. Wnt and Notch signaling govern self-renewal and differentiation in a subset of human glioblastoma stem cells. Genes Dev 2019; 33(9-10): 498-510.
[http://dx.doi.org/10.1101/gad.321968.118] [PMID: 30842215]
[57]
Seger R, Krebs EG. The MAPK signaling cascade. FASEB J 1995; 9(9): 726-35.
[http://dx.doi.org/10.1096/fasebj.9.9.7601337] [PMID: 7601337]
[58]
Shi C, Zhan L, Wu Y, et al. Kaji-Ichigoside F1 and rosamultin protect vascular endothelial cells against Hypoxia-induced apoptosis via the PI3K/AKT or ERK1/2 signaling pathway. Oxid Med Cell Longev 2020; 2020: 6837982.
[http://dx.doi.org/10.1155/2020/6837982] [PMID: 32318240]
[59]
Xu X, You K, Bu R. Proximal tubular development is impaired with downregulation of MAPK/ERK signaling, HIF-1α, and catalase by hyperoxia exposure in neonatal rats. Oxid Med Cell Longev 2019; 2019: 9219847.
[http://dx.doi.org/10.1155/2019/9219847] [PMID: 31558952]
[60]
Kučera J, Netušilová J, Sladeček S, et al. Hypoxia downregulates MAPK/ERK but not STAT3 signaling in ROS-dependent and HIF-1-Independent manners in mouse embryonic stem cells. Oxid Med Cell Longev 2017; 2017: 4386947.
[http://dx.doi.org/10.1155/2017/4386947] [PMID: 28819544]
[61]
Guan QH, Pei DS, Zong YY, Xu TL, Zhang GY. Neuroprotection against ischemic brain injury by a small peptide inhibitor of c-Jun N-terminal kinase (JNK) via nuclear and non-nuclear pathways. Neuroscience 2006; 139(2): 609-27.
[http://dx.doi.org/10.1016/j.neuroscience.2005.11.067] [PMID: 16504411]
[62]
Ferrer I, Friguls B, Dalfó E, Planas AM. Early modifications in the expression of mitogen-activated protein kinase (MAPK/ERK), stress-activated kinases SAPK/JNK and p38, and their phosphorylated substrates following focal cerebral ischemia. Acta Neuropathol 2003; 105(5): 425-37.
[http://dx.doi.org/10.1007/s00401-002-0661-2] [PMID: 12677442]
[63]
Xia P, Zhang F, Yuan Y, et al. ALDH 2 conferred neuroprotection on cerebral ischemic injury by alleviating mitochondria-related apoptosis through JNK/caspase-3 signing pathway. Int J Biol Sci 2020; 16(8): 1303-23.
[http://dx.doi.org/10.7150/ijbs.38962] [PMID: 32210721]
[64]
Xian XH, Gao JX, Qi J, Fan SJ, Zhang M, Li WB. Activation of p38 MAPK participates in the sulbactam-induced cerebral ischemic tolerance mediated by glial glutamate transporter-1 upregulation in rats. Sci Rep 2020; 10(1): 20601.
[http://dx.doi.org/10.1038/s41598-020-77583-0] [PMID: 33244020]
[65]
Sun Y, Zhu Y, Zhong X, Chen X, Wang J, Ying G. Crosstalk between autophagy and cerebral ischemia. Front Neurosci 2019; 12: 1022.
[http://dx.doi.org/10.3389/fnins.2018.01022] [PMID: 30692904]
[66]
Yamazaki Y, Arita K, Harada S, Tokuyama S. Activation of c-Jun N-terminal kinase and p38 after cerebral ischemia upregulates cerebral sodium-glucose transporter type 1. J Pharmacol Sci 2018; 138(4): 240-6.
[http://dx.doi.org/10.1016/j.jphs.2017.02.016] [PMID: 30503674]
[67]
Sawe N, Steinberg G, Zhao H. Dual roles of the MAPK/ERK1/2 cell signaling pathway after stroke. J Neurosci Res 2008; 86(8): 1659-69.
[http://dx.doi.org/10.1002/jnr.21604] [PMID: 18189318]
[68]
Irving EA, Barone FC, Reith AD, Hadingham SJ, Parsons AA. Differential activation of MAPK/ERK and p38/SAPK in neurones and glia following focal cerebral ischaemia in the rat. Brain Res Mol Brain Res 2000; 77(1): 65-75.
[http://dx.doi.org/10.1016/S0169-328X(00)00043-7] [PMID: 10814833]
[69]
Ferrer I, Planas AM. Signaling of cell death and cell survival following focal cerebral ischemia: Life and death struggle in the penumbra. J Neuropathol Exp Neurol 2003; 62(4): 329-39.
[http://dx.doi.org/10.1093/jnen/62.4.329] [PMID: 12722825]
[70]
Sun X, Zhou H, Luo X, et al. Neuroprotection of brain-derived neurotrophic factor against hypoxic injury in vitro requires activation of extracellular signal-regulated kinase and phosphatidylinositol 3-kinase. Int J Dev Neurosci 2008; 26(3-4): 363-70.
[http://dx.doi.org/10.1016/j.ijdevneu.2007.11.005] [PMID: 18243629]
[71]
Xu D, Kong T, Zhang S, Cheng B, Chen J, Wang C. Orexin-A protects against cerebral ischemia-reperfusion injury by inhibiting excessive autophagy through OX1R-mediated MAPK/ERK/mTOR pathway. Cell Signal 2021; 79: 109839.
[http://dx.doi.org/10.1016/j.cellsig.2020.109839] [PMID: 33212156]
[72]
Maddahi A, Edvinsson L. Cerebral ischemia induces microvascular pro-inflammatory cytokine expression via the MEK/ERK pathway. J Neuroinflammation 2010; 7: 14.
[http://dx.doi.org/10.1186/1742-2094-7-14] [PMID: 20187933]
[73]
Wang ZQ, Wu DC, Huang FP, Yang GY. Inhibition of MEK/ERK 1/2 pathway reduces pro-inflammatory cytokine interleukin-1 expression in focal cerebral ischemia. Brain Res 2004; 996(1): 55-66.
[http://dx.doi.org/10.1016/j.brainres.2003.09.074] [PMID: 14670631]
[74]
Wang T, Zhai L, Zhang H, Zhao L, Guo Y. Picroside II inhibits the MEK-ERK1/2-COX2 signal pathway to prevent cerebral ischemic injury in rats. J Mol Neurosci 2015; 57(3): 335-51.
[http://dx.doi.org/10.1007/s12031-015-0623-5] [PMID: 26240040]
[75]
Wu L, Xiong X, Wu X, et al. Targeting oxidative stress and inflammation to prevent ischemia-reperfusion injury. Front Mol Neurosci 2020; 13: 28.
[http://dx.doi.org/10.3389/fnmol.2020.00028] [PMID: 32194375]
[76]
Chen H, He Y, Chen S, Qi S, Shen J. Therapeutic targets of oxidative/nitrosative stress and neuroinflammation in ischemic stroke: Applications for natural product efficacy with omics and systemic biology. Pharmacol Res 2020; 158: 104877.
[http://dx.doi.org/10.1016/j.phrs.2020.104877] [PMID: 32407958]
[77]
Wang H, Xu L, Venkatachalam S, et al. Differential regulation of IL-1beta and TNF-alpha RNA expression by MEK1 inhibitor after focal cerebral ischemia in mice. Biochem Biophys Res Commun 2001; 286(5): 869-74.
[http://dx.doi.org/10.1006/bbrc.2001.5482] [PMID: 11527379]

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