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缺血性脑卒中的机制研究进展

樊文香

樊文香. 缺血性脑卒中的机制研究进展[J]. 中国药科大学学报, 2018, 49(6): 751-759. DOI: 10.11665/j.issn.1000-5048.20180618
引用本文: 樊文香. 缺血性脑卒中的机制研究进展[J]. 中国药科大学学报, 2018, 49(6): 751-759. DOI: 10.11665/j.issn.1000-5048.20180618
shu
FAN Wenxiang. Research progress on the mechanism of ischemic stroke[J]. Journal of China Pharmaceutical University, 2018, 49(6): 751-759. DOI: 10.11665/j.issn.1000-5048.20180618
Citation: FAN Wenxiang. Research progress on the mechanism of ischemic stroke[J]. Journal of China Pharmaceutical University, 2018, 49(6): 751-759. DOI: 10.11665/j.issn.1000-5048.20180618
shu

缺血性脑卒中的机制研究进展

  • 东南大学附属中大医院药学部

Research progress on the mechanism of ischemic stroke

摘要

    摘要
  • 摘要: 脑卒中是严重危害人类健康的疾病之一，由于缺乏对缺血后引起神经元细胞死亡的细胞和分子机制的深入了解，目前缺乏有效治疗手段。本文从细胞凋亡、兴奋性毒性、氧化和硝化应激、炎症反应、先天和适应性免疫细胞、肠道菌群以及颅内动脉粥样硬化等方面，对缺血性脑卒中的病理生理基础进行综述，并揭示其相互交织的信号通路机制，寻找可以有效治疗缺血性脑卒中的靶点，为开发缺血性脑卒中的治疗方案奠定基础。
    Abstract: Stroke is one of the diseases that seriously endanger human health without effective treatment at present, due to the lack of in-depth understanding of the cellular and molecular mechanisms underlying neuronal cell death after ischemia. In the present article, in order to lay the foundations for the development of therapeutic regimens for ischemic stroke, we review the underlying pathophysiology of ischemic stroke including apoptosis, excitotoxicity, oxidative and nitrative stress, inflammation, innate and adaptive immune cells, the gutmicrobiota and intracranial atherosclerosis, and reveal the intertwinedpathways that are promising therapeutic targets.
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    • 参考文献(66)
  • [1] Hossmann KA. Pathophysiology and therapy of experimental stroke[J].Cell Mol Neurobiol,2006,26(7/8):1055-1081.
    [2] Pandya RS,Mao L,Zhou H,et al.Central nervous system agents for ischemic stroke:neuroprotection mechanisms[J].Cent Nerv Syst Agents Med Chem,2011,11(2):81-97.
    [3] Tsuchiya M,Sako K,Yura S,et al.Cerebral blood flow and histopathological changes following permanent bilateral carotid artery ligation in Wistar rats[J].Exp Brain Res,1992,89(1):87-92.
    [4] Beal CC.Gender and stroke symptoms:a review of the current literature[J].J Neurosci Nurs,2010,42(2):80-87.
    [5] Siesjo BK.Pathophysiology and treatment of focal cerebral ischemia.II:mechanisms of damage and treatment[J].J Neurosurg,1992,77:337-354.
    [6] Titomanlio L,Fernandez-Lopez D,Manganozzi L,et al.Pathophysiology and neuroprotection of global and focal perinatal brain Injury:lessons from animal models[J].Pediatr Neurol,2015,52(6):566-584.
    [7] Li H,Colbourne F,Sun P,et al.Caspase inhibitors reduce neuronal injury after focal but not global cerebral ischemia in rats[J].Stroke,2000,31(1):176-182.
    [8] Hickey EJ,You X,Kaimaktchiev V,et al.Lipopolysaccharide preconditioning induces robust protection against brain injury resulting from deep hypothermic circulatory arrest[J].J Thorac Cardiovasc Surg,2007,133(6):1588-1596.
    [9] Ferrer I,Planas AM.Signaling of cell death and cell survival following focal cerebral ischemia:life and death struggle in the penumbra[J].J Neuropathol Exp Neurol,2003,62(4):329-339.
    [10] Huang W,Liu X,Cao J,et al.miR-134 regulates ischemia/reperfusion injury-induced neuronal cell death by regulating CREB signaling[J].J Mol Neurosci,2015,55(4):821-829.
    [11] Gonzalez RG,Hirsch JA,Koroshetz WJ,et al.Acute ischemic stroke.Imaging and intervention[J].J Neuroradiology,2006,33(3):193.
    [12] Mayor D,Tymianski M.Neurotransmitters in the mediation of cerebral ischemic injury[J].Neuropharmacology,2018,134:178-188.
    [13] Olney JW,Price MT,Samson L,et al.The role of specific ions in glutamate neurotoxicity[J].Neurosci Lett,1986,65(1):65-71.
    [14] Rothman SM.The neurotoxicity of excitatory amino acids is produced by passive chloride influx[J].J Neurosci,1985,5(6):1483-1489.
    [15] Tymianski M,Charlton MP,Carlen PL,et al.Secondary Ca2+ overload indicates early neuronal injury which precedes staining with viability indicators[J].Brain Res,1993,607(1/2):319-323.
    [16] Lai TW,Zhang S,Wang YT.Excitotoxicity and stroke:identifying novel targets for neuroprotection[J].Prog Neurobiol,2014,115(2):157-188.
    [17] Menon D.Ischemic stroke:from basic mechanisms to new drug development[J].J Neurol Neurosurg Psychiatry,1998,65(6):959.
    [18] Arundine M,Tymianski M.Molecular mechanisms of calcium-dependent neurodegeneration in excitotoxicity[J].Cell Calcium,2003,34(4/5):325-337.
    [19] Lai T W,Zhang S,Wang Y T.Excitotoxicity and stroke:identifying novel targets for neuroprotection[J].Prog Neurobiol,2014,115(2):157-188.
    [20] Sattler R, Tymianski M. Molecular mechanisms of calcium-dependent excitotoxicity[J].J Mol Med,2000,78(1):3-13.
    [21] Szydlowska K,Tymianski M.Calcium,ischemia and excitotoxicity[J].Cell Calcium,2010,47(2):122-129.
    [22] Yagami T,Ueda K,Sakaeda T,et al.Protective effects of a selective L-type voltage-sensitive calcium channel blocker,S-312-d,on neuronal cell death[J].Biochem Pharmacol,2004,67(6):1153-1165.
    [23] Sattler R,Charlton MP,Hafner M,et al.Distinct influx pathways,not calcium load,determine neuronal vulnerability to calcium neurotoxicity[J].J Neurochem,1998,71(6):2349-2364.
    [24] Tymianski M,Charlton MP,Carlen PL,et al.Source specificity of early calcium neurotoxicity in cultured embryonic spinal neurons[J].J Neurosci,1993,13(5):2085-2104.
    [25] Trudeau LE,Parpura V,Haydon PG.Activation of neurotransmitter release in hippocampal nerve terminals during recovery from intracellular acidification[J].J Neurophysiol,1999,81(6):2627-2635.
    [26] Boscia F,Gala R,Pignataro G,et al.Permanent focal brain ischemia induces isoform-dependent changes in the pattern of Na+/Ca2+ exchanger gene expression in the ischemic core,periinfarct area,and intact brain regions[J].J Cerebral Blood F Met,2006,26(4):502-517.
    [27] Lee BK,Lee DH,Park S,et al.Effects of KR-33028,a novel Na+/H+ exchanger-1 inhibitor,on glutamate-induced neuronal cell death and ischemia-induced cerebral infarct[J].Brain Res,2009,1248:22-30.
    [28] Bano D,Young KW,Guerin CJ,et al.Cleavage of the plasma membrane Na+/Ca2+ exchanger in excitotoxicity[J].Cell,2005,120(2):275-285.
    [29] White RJ,Reynolds IJ.Mitochondria accumulate Ca2+ following intense glutamate stimulation of cultured rat forebrain neurones[J].J Physiol,1997,498(1):31-47.
    [30] Castilho RF,Hansson O,Ward MW,et al.Mitochondrial control of acute glutamate excitotoxicity in cultured cerebellar granule cells[J].J Neurosci,1998,18(24):10277-10286.
    [31] Randall RD,Thayer SA.Glutamate-induced calcium transient triggers delayed calcium overload and neurotoxicity in rat hippocampal neurons[J].J Neurosci,1992,12(5):1882-1895.
    [32] Baudry M,Greget R,Pernot F,et al.Roles of group I metabotropic glutamate receptors under physiological conditions and in neurodegeneration[J].Wiley Interdiscip Rev Syst Biol Med,2012,1(4):523-532.
    [33] Rong R,Ahn JY,Huang H,et al.PI3 kinase enhancer-Homer complex couples mGluRI to PI3 kinase,preventing neuronal apoptosis[J].Nat Neurosci,2003,6(11):1153-1161.
    [34] Bruno V, Battaglia G, Copani A, et al. Metabotropic glutamate receptor subtypes as targets for neuroprotective drugs[J].J Cerebral Blood F Met,2001,21(9):1013-1033.
    [35] Fang Q,Hu WW,Wang XF,et al.Histamine up-regulates astrocytic glutamate transporter 1 and protects neurons against ischemic injury[J].Neuropharmacology,2014,77(2):156-166.
    [36] Lee JM,Zipfel GJ,Choi DW.The changing landscape of ischaemic brain injury mechanisms[J].Nature,1999,399(6738 Suppl):A7-14.
    [37] Liu Y,Wong TP,Aarts M,et al.NMDA receptor subunits have differential roles in mediating excitotoxic neuronal death both in vitro and in vivo[J].J Neurosci,2007,27(11):2846-2857.
    [38] Traynelis SF,Wollmuth LP,Mcbain CJ,et al.Glutamate receptor ion channels:structure,regulation,and function[J].Pharmacol Rev,2010,62(3):405-496.
    [39] Terasaki Y, Sasaki TY, Okazaki S, et al. Activation of NR2A receptors induces ischemic tolerance through CREB signaling[J].J Cerebral Blood F Met,2010,30(8):1441-1449.
    [40] Xu J,Kurup P,Zhang Y,et al.Extrasynaptic NMDA receptors couple preferentially to excitotoxicity via calpain-mediated cleavage of STEP[J].J Neurosci,2009,29(29):9330-9343.
    [41] Sugawara T,Chan P H.Reactive oxygen radicals and pathogenesis of neuronal death after cerebral ischemia[J].Antioxid Redox Signal,2003,5(5):597-607.
    [42] Girouard H,Wang G,Gallo EF,et al.NMDA receptor activation increases free radical production through nitric oxide and NOX2[J].J Neurosci,2009,29(8):2545-2552.
    [43] Wei EP,Kontos HA,Beckman JS.Mechanisms of cerebral vasodilation by superoxide,hydrogen peroxide,and peroxynitrite[J].Am J Physiol,1996,271(3 Pt 2):H1262-1266.
    [44] Alfieri A,Srivastava S,Siow RC,et al.Targeting the Nrf2-Keap1 antioxidant defence pathway for neurovascular protection in stroke[J].J Physiol,2011,589(Pt 17):4125-4136.
    [45] Ren Y,Su M,Zheng J,et al.Protective effects of Naomaili granules on cerebral ischemia-reperfusion in rats and its mechanism[J].J China Pharm Univ(中国药科大学学报),2015,46(1):100-104.
    [46] Shuai J,Chao D,Lv J,et al.Nrf2 weaves an elaborate network of neuroprotection against stroke[J].Mol Neurobiol,2017,54(2):1440-1455.
    [47] Fernandes A,Miller-Fleming L,Pais TF.Microglia and inflammation:conspiracy,controversy or control[J]?Cell Mol Life Sci,2014,71(20):3969-3985.
    [48] Kim B,Jeong HK,Kim JH,et al.Uridine 5′-diphosphate induces chemokine expression in microglia and astrocytes through activation of the P2Y6 receptor[J].J Immunol,2011,186(6):3701-3709.
    [49] Fu Y,Liu Q,Anrather J,et al.Immune interventions in stroke[J].Nat Rev Neurol,2015,11(9):524-535.
    [50] Doyle KP,Simon RP,Stenzel-Poore MP.Mechanisms of ischemic brain damage[J].Neuropharmacology,2008,55(3):310-318.
    [51] Bo L,Peterson JW,Mork S,et al.Distribution of immunoglobulin superfamily members ICAM-1,-2,-3,and the beta 2 integrin LFA-1 in multiple sclerosis lesions[J].J Neuropathol Exp Neurol,1996,55(10):1060-1072.
    [52] Huang J,Upadhyay UM,Tamargo RJ.Inflammation in stroke and focal cerebral ischemia[J].Surg Neurol,2006,66(3):232-245.
    [53] Maria E,Albert Q,Juan H.Interleukin-6,a major cytokine in the central nervous system[J].Int J Biol Sci,2012,8(9):1254-1266.
    [54] Park KP,Rosell A,Foerch C,et al.Plasma and brain matrix metalloproteinase-9 after acute focal cerebral ischemia in rats[J].Stroke,2009,40(8):2836-2842.
    [55] Yao L,Kan EM,Lu J,et al.Toll-like receptor 4 mediates microglial activation and production of inflammatory mediators in neonatal rat brain following hypoxia:role of TLR4 in hypoxic microglia[J].J Neuroinflammation,2013,10(1):785-805.
    [56] Bohacek I,Cordeau P,Lalancettehebert M,et al.Toll-like receptor 2 deficiency leads to delayed exacerbation of ischemic injury[J].J Neuroinflammation,2012,9(1):191.
    [57] Petrovic Djergovic D,Goonewardena SN,Pinsky DJ.Inflammatory disequilibrium in stroke[J].Circ Res,2016,119(1):142-158.
    [58] Jr CTA,Collier LA,Leonardo CC,et al.Blockade of adrenoreceptors inhibits the splenic response to stroke[J].Exp Neurol,2009,218(1):47-55.
    [59] Akiyoshi K,Ren X,Dziennis S,et al.Regulatory B-cells limit CNS inflammation and neurologic deficits in murine experimental stroke[J].J Neurosci,2011,31(23):8556-8563.
    [60] Benakis C, Brea D, Caballero S, et al. Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδ T cells[J].Nat Med,2016,22:516-523.
    [61] Singh V,Roth S,Llovera G,et al.Microbiota dysbiosis controls the neuroinflammatory response after stroke[J].J Neurosci,2016,36(28):7428-7440.
    [62] Yin J, Liao SX, He Y, et al. Dysbiosis of gut microbiota with reduced trimethylamine-N-oxide level in patients with large-artery atherosclerotic stroke or transient ischemic attack[J].J Am Heart Assoc,2015,4(11):e002699.
    [63] Karlsson FH,Fak F,Nookaew I,et al.Symptomatic atherosclerosis is associated with an altered gut metagenome[J].Nat Commun,2012,3:1245.
    [64] Arvanitakis Z,Capuano AW,Leurgans SE,et al.Relation of cerebral vessel disease to Alzheimer′s disease dementia and cognitive function in elderly people:a cross-sectional study[J].Lancet Neurol,2016,15(9):934-943.
    [65] Ajay G,Costantino I.Impaired Aβ clearance:a potential link between atherosclerosis and Alzheimer′s disease[J].Front Aging Neurosci,2015,7:115.
    [66] Zhu W,Gregory JC,Org E,et al.Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk[J].Cell,2016,165(1):111-124.
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  • 刊出日期:  2018-12-24

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