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浙江大学学报(医学版)  2018, Vol. 47 Issue (5): 493-498    DOI: 10.3785/j.issn.1008-9292.2018.10.08
专题报道     
星形胶质细胞在脑梗死中的作用及相关治疗策略
叶建宇1(),孙自玉1,胡薇薇2,*()
1. 浙江大学药学院, 浙江 杭州 310058
2. 浙江大学医学院药理学系, 浙江 杭州 310058
Roles of astrocytes in cerebral infarction and related therapeutic strategies
YE Jianyu1(),SUN Ziyu1,HU Weiwei2,*()
1. College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
2. Department of Pharmacology, School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou 310058, China
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摘要:

星形胶质细胞是中枢神经系统中最丰富的细胞,在大脑正常生理过程中扮演重要角色。脑梗死发生后,星形胶质细胞激活成为反应性星形胶质细胞,并形成胶质瘢痕,在脑损伤过程中发挥重要作用。根据其在脑梗死后神经保护、调节瘢痕形成、神经再生、维持血脑屏障和促进血管生成、调节免疫应答等方面的作用,学者们提出了靶向星形胶质细胞的多种治疗策略。本文就反应性星形胶质细胞在脑梗死后发挥的积极作用以及相应的治疗策略作一综述。

关键词: 脑梗死星形细胞瘢痕/病因学综述    
Abstract:

Astrocytes are the most abundant cells in the central nervous system and play significant roles in normal brain. With cerebral infarction, astrocytes are activated as reactive astrocytes and form glial scars, which play an essential part in brain injury. According to their roles in neuroprotection after cerebral infarction, regulation of scar formation, nerve regeneration, maintenance of blood-brain barrier, promotion of angiogenesis and immune response, scholars have proposed a variety of therapeutic strategies based on targeting astrocytes. This article reviews the research progress on the changes in astrocyte signaling pathways before and after cerebral infarction and the related therapeutic strategies.

Key words: Brain infarction    Astrocytes    Cicatrix/etiology    Review
收稿日期: 2018-05-30 出版日期: 2019-01-23
:  R743  
基金资助: 浙江大学第二十期大学生科研训练计划(SRTP)(X20170274)
通讯作者: 胡薇薇     E-mail: 3150103114@zju.edu.cn;huww@zju.edu.cn
作者简介: 叶建宇(1997-), 男, 主要从事细胞生物学研究; E-mail:3150103114@zju.edu.cn; https://orcid.org/0000-0003-1530-0295
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引用本文:

叶建宇,孙自玉,胡薇薇. 星形胶质细胞在脑梗死中的作用及相关治疗策略[J]. 浙江大学学报(医学版), 2018, 47(5): 493-498.

YE Jianyu,SUN Ziyu,HU Weiwei. Roles of astrocytes in cerebral infarction and related therapeutic strategies. J Zhejiang Univ (Med Sci), 2018, 47(5): 493-498.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2018.10.08        http://www.zjujournals.com/med/CN/Y2018/V47/I5/493

1 GORSHKOV K , AGUISANDA F , THORNE N et al. Astrocytes as targets for drug discovery[J]. Drug Discov Today, 2018, 23 (3): 673- 680
2 CHEN J , HE W , HU X et al. A role for ErbB signaling in the induction of reactive astrogliosis[J]. Cell Discov, 2017, 3:17044
doi: 10.1038/celldisc.2017.44
3 LECOMTE M D , SHIMADA I S , SHERWIN C et al. Notch1-STAT3-ETBR signaling axis controls reactive astrocyte proliferation after brain injury[J]. Proc Natl Acad Sci USA, 2015, 112 (28): 8726- 8731
doi: 10.1073/pnas.1501029112
4 LIDDELOW S A , GUTTENPLAN K A , CLARKE L E et al. Neurotoxic reactive astrocytes are induced by activated microglia[J]. Nature, 2017, 541 (7638): 481- 487
doi: 10.1038/nature21029
5 LIAO R J , JIANG L , WANG R R et al. Histidine provides long-term neuroprotection after cerebral ischemia through promoting astrocyte migration[J]. Sci Rep, 2015, 5:15356
doi: 10.1038/srep15356
6 HAYAKAWA K , ESPOSITO E , WANG X et al. Transfer of mitochondria from astrocytes to neurons after stroke[J]. Nature, 2016, 535 (7613): 551- 555
doi: 10.1038/nature18928
7 MISHRA A , REYNOLDS J P , CHEN Y et al. Astrocytes mediate neurovascular signaling to capillary pericytes but not to arterioles[J]. Nat Neurosci, 2016, 19 (12): 1619- 1627
doi: 10.1038/nn.4428
8 BECERRACALIXTO A , CARDONAGíMEZ G P . The role of astrocytes in neuroprotection after brain stroke:potential in cell therapy[J]. Front Mol Neurosci, 2017, 10 (159): 88
9 TAKANO K , OGAWA M , KAWABE K et al. Inhibition of gap junction elevates glutamate uptake in cultured astrocytes[J]. Neurochem Res, 2018, 43 (1): 50- 56
doi: 10.1007/s11064-017-2316-7
10 VERMEHREN P , TROTMANLUCAS M , HECHLER B et al. Cooperation between NMDA-type glutamate and P2 receptors for neuroprotection during stroke:combining astrocyte and neuronal protection[J]. Neuroglia, 2018, 1 (1): 5
11 DOMITH I , SOCODATO R , PORTUGAL C C et al. Vitamin C modulates glutamate transport and NMDA receptor function in the retina[J]. J Neurochem, 2018, 144 (4): 408- 420
doi: 10.1111/jnc.2018.144.issue-4
12 MANGAS A , YAJEYA J , GONZáLEZ N et al. Overexpression of kynurenic acid in stroke:an endogenous neuroprotector?[J]. Ann Anat, 2017, 211:33- 38
doi: 10.1016/j.aanat.2017.01.002
13 GUO X , JIANG Q , TUCCITTO A et al. The AMPK-PGC-1α signaling axis regulates the astrocyte glutathione system to protect against oxidative and metabolic injury[J]. Neurobiol Dis, 2018, 113:59- 69
doi: 10.1016/j.nbd.2018.02.004
14 GUITART K , LOERS G , BUCK F et al. Improvement of neuronal cell survival by astrocyte-derived exosomes under hypoxic and ischemic conditions depends on prion protein[J]. Glia, 2016, 64 (6): 896- 910
15 LIU Z , CHOPP M . Astrocytes, therapeutic targets for neuroprotection and neurorestoration in ischemic stroke[J]. Prog Neurobiol, 2016, 144:103- 120
doi: 10.1016/j.pneurobio.2015.09.008
16 YE L, YANG Y, ZHANG X, et al. The role of bFGF in the excessive activation of astrocytes is related to the inhibition of TLR4/NFκB signals[J/OL]. Int J Mol Sci, 2015, 17(1): E37.
17 陈戟, 谭秀华, 庞韬 et al. 右美托咪定对全脑缺氧缺血损伤大鼠海马内星形胶质细胞VEGF表达的影响[J]. 实用药物与临床, 2017, 20 (3): 241- 245
CHEN Ji , TAN Xiuhua , PANG Tao et al. Influences of dexmedetomidine on VEGF expressions of hippocampal astrocytes in rats with hypoxic-ischemic brain damage[J]. Practical Pharmacy and Clinical Remedies, 2017, 20 (3): 241- 245
18 ZHANG Y , HONG G , LEE K S et al. Inhibition of soluble epoxide hydrolase augments astrocyte release of vascular endothelial growth factor and neuronal recovery after oxygen-glucose deprivation[J]. J Neurochem, 2017, 140 (5): 814- 825
doi: 10.1111/jnc.13933
19 HUI S , MING J , XING F et al. Mesencephalic astrocyte-derived neurotrophic factor reduces cell apoptosis via upregulating HSP70 in SHSY-5Y cells[J]. Transl Neurodegener, 2017, 6 (1): 12
20 WANG X Y, SONG M M, BI S X, et al. MRI dynamically evaluates the therapeutic effect of recombinant human MANF on ischemia/reperfusion injury in rats[J/OL]. Int J Mol Sci, 2016, 17(9): E1476.
21 ZHAO Y , ZHANG Q , CHEN Z et al. Simvastatin combined with bone marrow stromal cells treatment activates astrocytes to ameliorate neurological function after ischemic stroke in rats[J]. Turk J Biol, 2016, 40 (2): 519- 528
22 ZHANG Q , CHEN Z W , ZHAO Y H et al. Bone marrow stromal cells combined with sodium ferulate and n-butylidenephthalide promote the effect of therapeutic angiogenesis via advancing astrocyte-derived trophic factors after ischemic stroke[J]. Cell Transplant, 2016, 26 (2): 229- 242
23 HUANG L , WU Z B , ZHUGE Q et al. Glial scar formation occurs in the human brain after ischemic stroke[J]. Int J Med Sci, 2014, 11 (4): 344- 348
doi: 10.7150/ijms.8140
24 ZBESKO J C , NGUYEN T V , YANG T et al. Glial scars are permeable to the neurotoxic environment of chronic stroke infarcts[J]. Neurobiol Dis, 2018, 112:63- 78
doi: 10.1016/j.nbd.2018.01.007
25 MOEENDARBARY E , WEBER I P , SHERIDAN G K et al. The soft mechanical signature of glial scars in the central nervous system[J]. Nat Commun, 2017, 8:14787
doi: 10.1038/ncomms14787
26 ABEYSINGHE H C S , PHILLIPS E L , CHINCHENG H et al. Modulating astrocyte transition after stroke to promote brain rescue and functional recovery:emerging targets include Rho kinase[J]. Int J Mol Sci, 2016, 17 (3): 288
doi: 10.3390/ijms17030288
27 CHEON S Y , CHO K J , SONG J et al. Knockdown of apoptosis signal-regulating kinase 1 affects ischaemia-induced astrocyte activation and glial scar formation[J]. Eur J Neurosci, 2016, 43 (7): 912- 922
doi: 10.1111/ejn.13175
28 YOSHIKAWA A , KAMIDE T , HASHIDA K et al. Deletion of Atf6α impairs astroglial activation and enhances neuronal death following brain ischemia in mice[J]. J Neurochem, 2015, 132 (3): 342- 353
doi: 10.1111/jnc.2015.132.issue-3
29 ZHANG H , LI Z S , NI Y et al. Abstract WMP38:inhibition of Rip1 kinase improves brain functional recovery after ischemic stroke via reducing astrocytic scar formation[J]. Stroke, 2017, 48 (suppl_1): :AWMP38
30 LEON T , JIHANE H L , JAMES B . Linking development and regeneration:ephrin-A1 attenuates glial scarring after adulthood stroke[J]. Front Cell Neurosci, 2016,
31 CHEN J , ZHANG J H , HU X M . Non-neuronal mechanisms of brain damage and repair after stroke[M]. Germany: Springer International Publishing, 2016: 111- 131
32 MAGNUSSON J P , G?RITZ C , TATARISHVILI J et al. A latent neurogenic program in astrocytes regulated by Notch signaling in the mouse[J]. Science, 2014, 346 (6206): 237- 241
doi: 10.1126/science.346.6206.237
33 MO J L , LIU Q , KOU Z W et al. MicroRNA-365 modulates astrocyte conversion into neuron in adult rat brain after stroke by targeting Pax6[J]. Glia, 2018, 66 (7): 1346- 1362
doi: 10.1002/glia.v66.7
34 SHINDO A , MAKI T , MANDEVILLE E T et al. Astrocyte-derived pentraxin 3 supports blood-brain barrier integrity under acute phase of stroke[J]. Stroke, 2016, 47 (4): 1094- 1100
doi: 10.1161/STROKEAHA.115.012133
35 ALVAREZ J I , DODELETDEVILLERS A , KEBIR H et al. The Hedgehog pathway promotes blood-brain barrier integrity and CNS immune quiescence[J]. Science, 2011, 334 (6063): 1727
doi: 10.1126/science.1206936
36 WANG Y, JIN S, SONOBE Y, et al. Interleukin-1β induces blood-brain barrier disruption by downregulating Sonic hedgehog in astrocytes[J/OL]. PLoS One, 2014, 9(10): e110024.
37 CHU H , YANG X , HUANG C et al. Apelin-13 protects against ischemic blood-brain barrier damage through the effects of aquaporin-4[J]. Cerebrovasc Dis, 2017, 44 (1-2): 10- 25
doi: 10.1159/000460261
38 HE Q W , XIA Y P , CHEN S C et al. Astrocyte-derived sonic hedgehog contributes to angiogenesis in brain microvascular endothelial cells via RhoA/ROCK pathway after oxygen-glucose deprivation[J]. Mol Neurobiol, 2013, 47 (3): 976- 987
doi: 10.1007/s12035-013-8396-8
39 LUO C , YI B , FAN W et al. Enhanced angiogenesis and astrocyte activation by ecdysterone treatment in a focal cerebral ischemia rat model[J]. Acta Neurochir Suppl, 2011, 110 (Pt1): 151- 155
40 WANG J , SHI Y , ZHANG L et al. Omega-3 polyunsaturated fatty acids enhance cerebral angiogenesis and provide long-term protection after stroke[J]. Neurobiol Dis, 2014, 68:91- 103
doi: 10.1016/j.nbd.2014.04.014
41 CEKANAVICIUTE E , FATHALI N , DOYLE K P et al. Astrocytic transforming growth factor-beta signaling reduces subacute neuroinflammation after stroke in mice[J]. Glia, 2014, 62 (8): 1227- 1240
doi: 10.1002/glia.22675
42 LI M, LI Z, YAO Y, et al. Astrocyte-derived interleukin-15 exacerbates ischemic brain injury via propagation of cellular immunity[J/OL]. Proc Natl Acad Sci USA, 2017, 114(3): E396-E405.
43 CHEN J , YE X , YAN T et al. Adverse effects of bone marrow stromal cell treatment of stroke in diabetic rats[J]. Stroke, 2011, 42 (12): 3551- 3558
doi: 10.1161/STROKEAHA.111.627174
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