靶向星形胶质细胞治疗缺血性脑卒中的研究进展
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摘要
缺血性脑卒中(ischemic stroke, IS)发生后,缺血区星形胶质细胞(astrocyte)活化,这些反应性星形胶质细胞对缺血区神经元发挥有利和有害双重作用。星形胶质细胞与IS诱导的谷氨酸功能障碍、线粒体功能障碍和胶质瘢痕形成密切相关,并且在IS后神经元网络重构中发挥重要调节作用。现重点探讨如何利用星形胶质细胞对IS发挥保护作用的研究进展。
Astrocytes are activated after ischemic stroke(IS). The astrocytes play both deleterious and beneficial roles in ischemic area. Astrocytes are involved in extracellular glutamate dysfunction, mitochondrial dysfunction and glial scar formation, and play an important regulatory role in neuronal network remodeling after IS. In this review, we will focus on the recent progresses regarding to the protection function of astrocytes in IS.
Astrocytes are activated after ischemic stroke(IS). The astrocytes play both deleterious and beneficial roles in ischemic area. Astrocytes are involved in extracellular glutamate dysfunction, mitochondrial dysfunction and glial scar formation, and play an important regulatory role in neuronal network remodeling after IS. In this review, we will focus on the recent progresses regarding to the protection function of astrocytes in IS.
引文
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[32]Ouyang L,Tian Y,Bao Y,et al.Carnosine decreased neuronal cell death through targeting glutamate system and astrocyte mitochondrial bioenergetics in cultured neuron/astrocyte exposed to OGD/recovery.Brain Res Bull,2016,124:76-84
[33]Zhao B,Shi QJ,Zhang ZZ,et al.Protective effects of paeonol on subacute/chronic brain injury during cerebral ischemia in rats.Exp Ther Med,2018,15:3836-46
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[37]Liu D,Zhang M,Rong X,et al.Potassium 2-(1-hydroxypentyl)-benzoate attenuates neuronal apoptosis in neuronastrocyte co-culture system through neurotrophy and neuroinflammation pathway.Acta Pharm Sin B,2017,7:554-63
[38]Huang X,Li Y,Li J,et al.Tanshinone IIA dampens the cell proliferation induced by ischemic insult in rat astrocytes via blocking the activation of HIF-1α/SDF-1signaling.Life Sci,2014,112:59-67
[39]Silver J,Miller JH.Regeneration beyond the glial scar.Nat Rev Neurosci,2004,5:146-56
[40]Voskuhl RR,Peterson RS,Song B,et al.Reactive astrocytes form scar-like perivascular barriers to leukocytes during adaptive immune inflammation of the CNS.JNeurosci,2009,29:11511-22
[41]Trendelenburg G,Dirnagl U.Neuroprotective role of astrocytes in cerebral ischemia:focus on ischemic preconditioning.Glia,2005,50:307-20
[42]Hayakawa K,Nakano T,Irie K,et al.Inhibition of reactive astrocytes with fluorocitrate retards neurovascular remodeling and recovery after focal cerebral ischemia in mice.J Cereb Blood Flow Metab,2010,30:871-82
[43]Bejot Y,Prigent-Tessier A,Cachia C,et al.Timedependent contribution of non neuronal cells to BDNFproduction after ischemic stroke in rats.Neurochem Int,2011,58:102-11
[44]Chen X,Zhang X,Liao W,et al.Effect of physical and social components of enriched environment on astrocytes proliferation in rats after cerebral ischemia/reperfusion injury.Neurochem Res,2017,42:1308-16
[2]Ding DC,Shyu WC,Lin SZ,et al.Current concepts in adult stem cell therapy for stroke.Curr Med Chem,2006,13:3565-74
[3]Becerra-Calixto A,Posada-Duque R,Cardona-Gomez GP.Recovery of neurovascular unit integrity by CDK5-KDastrocyte transplantation in a global cerebral ischemia model.Mol Neurobiol,2018,55:8563-85
[4]Liu Z,Chopp M.Astrocytes,therapeutic targets for neuroprotection and neurorestoration in ischemic stroke.Prog Neurobiol,2016,144:103-20
[5]Sun L,Zhang Y,Liu E,et al.The roles of astrocyte in the brain pathologies following ischemic stroke.Brain Inj,2018:1-5
[6]Burda JE,Sofroniew MV.Reactive gliosis and the multicellular response to CNS damage and disease.Neuron,2014,81:229-48
[7]Middeldorp J,Hol EM.GFAP in health and disease.Prog Neurobiol,2011,93:421-43
[8]Allen NJ,Bennett ML,Foo LC,et al.Astrocyte glypicans4 and 6 promote formation of excitatory synapses via GluA1 AMPA receptors.Nature,2012,486:410-4
[9]Jung YJ,Chung WS.Phagocytic roles of glial cells in healthy and diseased brains.Biomol Ther(Seoul),2018,26:350-7
[10]Liddelow SA,Guttenplan KA,Clarke LE,et al.Neurotoxic reactive astrocytes are induced by activated microglia.Nature,2017,541:481-7
[11]Sofroniew MV,Vinters HV.Astrocytes:biology and pathology.Acta Neuropathol,2010,119:7-35
[12]Herrmann JE,Imura T,Song B,et al.STAT3 is a critical regulator of astrogliosis and scar formation after spinal cord injury.J Neurosci,2008,28:7231-43
[13]Sims NR,Yew WP.Reactive astrogliosis in stroke:contributions of astrocytes to recovery of neurological function.Neurochem Int,2017,107:88-103
[14]Diaz A,Merino P,Manrique LG,et al.A cross talk between neuronal urokinase-type plasminogen activator(uPA)and astrocytic uPA receptor(uPAR)promotes astrocytic activation and synaptic recovery in the ischemic brain.J Neurosci,2017,37:10310-22
[15]Lee GA,Lai YG,Chen RJ,et al.Interleukin 15 activates Akt to protect astrocytes from oxygen glucose deprivationinduced cell death.Cytokine,2017,92:68-74
[16]Li M,Li Z,Yao Y,et al.Astrocyte-derived interleukin-15exacerbates ischemic brain injury via propagation of cellular immunity.Proc Natl Acad Sci USA,2017,114:E396-405
[17]Li S,Dai Q,Yu J,et al.Identification of IL-17A-derived neural cell type and dynamic changes of IL-17A in serum/CSF of mice with ischemic stroke.Neurol Res,2017,39:552-8
[18]Lin Y,Zhang JC,Yao CY,et al.Critical role of astrocytic interleukin-17 A in post-stroke survival and neuronal differentiation of neural precursor cells in adult mice.Cell Death Dis,2016,7:e2273
[19]Zhang Y,Xu D,Qi H,et al.Enriched environment promotes post-stroke neurogenesis through NF-κB-mediated secretion of IL-17A from astrocytes.Brain Res,2018,1687:20-31
[20]Chen J,Zhang DM,Feng X,et al.TIGAR inhibits ischemia/reperfusion-induced inflammatory response of astrocytes.Neuropharmacology,2018,131:377-88
[21]Mo JL,Liu Q,Kou ZW,et al.MicroRNA-365 modulates astrocyte conversion into neuron in adult rat brain after stroke by targeting Pax6.Glia,2018,66:1346-62
[22]Ghosh M,Lane M,Krizman E,et al.The transcription factor Pax6 contributes to the induction of GLT-1expression in astrocytes through an interaction with a distal enhancer element.J Neurochem,2016,136:262-75
[23]Sun XD,Li L,Liu F,et al.Lrp4 in astrocytes modulates glutamatergic transmission.Nat Neurosci,2016,19:1010-8
[24]Ye XC,Hu JX,Li L,et al.Astrocytic Lrp4 contributes to ischemia-induced brain injury by regulating ATP release and adenosine-A2AR signaling.Stroke,2018,49:165-74
[25]Becerra-Calixto A,Cardona-Gomez GP.Neuroprotection induced by transplanted CDK5 knockdown astrocytes in global cerebral ischemic rats.Mol Neurobiol,2017,54:6681-96
[26]Posada-Duque RA,Palacio-Castaneda V,Cardona-Gomez GP.CDK5 knockdown in astrocytes provide neuroprotection as a trophic source via Rac1.Mol Cell Neurosci,2015,68:151-66
[27]Ji YB,Zhuang PP,Ji Z,et al.TFP5 peptide,derived from CDK5-activating cofactor p35,provides neuroprotection in early-stage of adult ischemic stroke.Sci Rep,2017,7:40013
[28]Rakers C,Petzold GC.Astrocytic calcium release mediates peri-infarct depolarizations in a rodent stroke model.J Clin Invest,2017,127:511-6
[29]Li HL,Xie YC,Zhang NN,et al.Disruption of IP3R2-mediated Ca2+signaling pathway in astrocytes ameliorates neuronal death and brain damage while reducing behavioral deficits after focal ischemic stroke.Cell Calcium,2015,58:565-76
[30]Halder SK,Ueda H.Amlexanox inhibits cerebral ischemia-induced delayed astrocytic high-mobility group box 1 release and subsequent brain damage.J Pharmacol Exp Ther,2018,365:27-36
[31]Ou-Yang L,Liu Y,Wang BY,et al.Carnosine suppresses oxygen-glucose deprivation/recovery-induced proliferation and migration of reactive astrocytes of rats in vitro.Acta Pharmacol Sin,2018,39:24-34
[32]Ouyang L,Tian Y,Bao Y,et al.Carnosine decreased neuronal cell death through targeting glutamate system and astrocyte mitochondrial bioenergetics in cultured neuron/astrocyte exposed to OGD/recovery.Brain Res Bull,2016,124:76-84
[33]Zhao B,Shi QJ,Zhang ZZ,et al.Protective effects of paeonol on subacute/chronic brain injury during cerebral ischemia in rats.Exp Ther Med,2018,15:3836-46
[34]Li CY,Li X,Liu SF,et al.Inhibition of mTOR pathway restrains astrocyte proliferation,migration and production of inflammatory mediators after oxygen-glucose deprivation and reoxygenation.Neurochem Int,2015,83-84:9-18
[35]Liu X,Tian F,Wang S,et al.Astrocyte autophagy flux protects neurons against oxygen-glucose deprivation and ischemic/reperfusion injury.Rejuvenation Res,2018,21:405-15
[36]Krzyzanowska W,Pomierny B,Bystrowska B,et al.Ceftriaxone-and N-acetylcysteine-induced brain tolerance to ischemia:influence on glutamate levels in focal cerebral ischemia.PLoS One,2017,12:e0186243
[37]Liu D,Zhang M,Rong X,et al.Potassium 2-(1-hydroxypentyl)-benzoate attenuates neuronal apoptosis in neuronastrocyte co-culture system through neurotrophy and neuroinflammation pathway.Acta Pharm Sin B,2017,7:554-63
[38]Huang X,Li Y,Li J,et al.Tanshinone IIA dampens the cell proliferation induced by ischemic insult in rat astrocytes via blocking the activation of HIF-1α/SDF-1signaling.Life Sci,2014,112:59-67
[39]Silver J,Miller JH.Regeneration beyond the glial scar.Nat Rev Neurosci,2004,5:146-56
[40]Voskuhl RR,Peterson RS,Song B,et al.Reactive astrocytes form scar-like perivascular barriers to leukocytes during adaptive immune inflammation of the CNS.JNeurosci,2009,29:11511-22
[41]Trendelenburg G,Dirnagl U.Neuroprotective role of astrocytes in cerebral ischemia:focus on ischemic preconditioning.Glia,2005,50:307-20
[42]Hayakawa K,Nakano T,Irie K,et al.Inhibition of reactive astrocytes with fluorocitrate retards neurovascular remodeling and recovery after focal cerebral ischemia in mice.J Cereb Blood Flow Metab,2010,30:871-82
[43]Bejot Y,Prigent-Tessier A,Cachia C,et al.Timedependent contribution of non neuronal cells to BDNFproduction after ischemic stroke in rats.Neurochem Int,2011,58:102-11
[44]Chen X,Zhang X,Liao W,et al.Effect of physical and social components of enriched environment on astrocytes proliferation in rats after cerebral ischemia/reperfusion injury.Neurochem Res,2017,42:1308-16