Abstract
Astrogliosis, a cellular reaction with specific structural and functional characteristics, represents a remarkably homotypic response of astrocytes to all kinds of central nervous system (CNS) pathologies. Astrocytes play diverse functions in the brain, both harmful and beneficial. Mounting evidence indicates that astrogliosis is an underlying component of a diverse range of diseases and associated neuropathologies. The mechanisms that lead to astrogliosis are not fully understood, nevertheless, damaged neurons have long been reported to induce astrogliosis and astrogliosis has been used as an index for underlying neuronal damage. As the predominant source of proinflammatory factors in the CNS, microglia are readily activated under certain pathological conditions. An increasing body of evidence suggests that release of cytokines and other soluble products by activated microglia can significantly influence the subsequent development of astrogliosis and scar formation in CNS. It is well known that damaged neurons activate microglia very quickly, therefore, it is possible that activated microglia contribute factors/mediators through which damaged neuron induce astrogliosis. The hypothesis that activated microglia initiate and maintain astrogliosis suggests that suppression of microglial overactivation might effectively attenuate reactive astrogliosis. Development of targeted anti-microglial activation therapies might slow or halt the progression of astrogliosis and, therefore, help achieve a more beneficial environment in various CNS pathologies.
Similar content being viewed by others
References
Malarkey EB, Parpura V (2008) Mechanisms of glutamate release from astrocytes. Neurochem Int 52:142–154
Bergami M, Santi S, Formaggio E, Cagnoli C, Verderio C, Blum R, Berninger B, Matteoli M, Canossa M (2008) Uptake and recycling of pro-BDNF for transmitter-induced secretion by cortical astrocytes. J Cell Biol 183:213–221
Bogen IL, Risa O, Haug KH, Sonnewald U, Fonnum F, Walaas SI (2008) Distinct changes in neuronal and astrocytic amino acid neurotransmitter metabolism in mice with reduced numbers of synaptic vesicles. J Neurochem 105:2524–2534
Araque A (2008) Astrocytes process synaptic information. Neuron Glia Biol 4:3–10
Hu R, Cai WQ, Wu XG, Yang Z (2007) Astrocyte-derived estrogen enhances synapse formation and synaptic transmission between cultured neonatal rat cortical neurons. Neuroscience 144:1229–1240
Ishibashi T, Dakin KA, Stevens B, Lee PR, Kozlov SV, Stewart CL, Fields RD (2006) Astrocytes promote myelination in response to electrical impulses. Neuron 49:823–832
Yamaguchi H, Kidachi Y, Umetsu H, Ryoyama K (2008) Differentiation of serum-free mouse embryo cells into an astrocytic lineage is associated with the asymmetric production of early neural, neuronal and glial markers. Biol Pharm Bull 31:1008–1012
Bundesen LQ, Scheel TA, Bregman BS, Kromer LF (2003) Ephrin-B2 and EphB2 regulation of astrocyte-meningeal fibroblast interactions in response to spinal cord lesions in adult rats. J Neurosci 23:7789–7800
Petros TJ, Williams SE, Mason CA (2006) Temporal regulation of EphA4 in astroglia during murine retinal and optic nerve development. Mol Cell Neurosci 32:49–66
Eng LF, Ghirnikar RS (1994) GFAP and astrogliosis. Brain Pathol 4:229–237
Guo Y, Liu Y, Xu L, Wu S, Yang C, Wu D, Wu H, Li C (2007) Astrocytic pathology in the immune-mediated motor neuron injury. Amyotroph Lateral Scler 8:230–234
Pannu R, Singh AK, Singh I (2005) A novel role of lactosylceramide in the regulation of tumor necrosis factor alpha-mediated proliferation of rat primary astrocytes. Implications for astrogliosis following neurotrauma. J Biol Chem 280:13742–13751
Reinhard JF Jr, Miller DB, O’Callaghan JP (1988) The neurotoxicant MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) increases glial fibrillary acidic protein and decreases dopamine levels of the mouse striatum: evidence for glial response to injury. Neurosci Lett 95:246–251
Zhang L, Zhang WP, Chen KD, Qian XD, Fang SH, Wei EQ (2007) Caffeic acid attenuates neuronal damage, astrogliosis and glial scar formation in mouse brain with cryoinjury. Life Sci 80:530–537
O’Callaghan JP (1991) Assessment of neurotoxicity: use of glial fibrillary acidic protein as a biomarker. Biomed Environ Sci 4:197–206
O’Callaghan JP (1994) Biochemical analysis of glial fibrillary acidic protein as a quantitative approach to neurotoxicity assessment: advantages, disadvantages and application to the assessment of NMDA receptor antagonist-induced neurotoxicity. Psychopharmacol Bull 30:549–554
O’Callaghan JP, Jensen KF (1992) Enhanced expression of glial fibrillary acidic protein and the cupric silver degeneration reaction can be used as sensitive and early indicators of neurotoxicity. Neurotoxicology 13:113–122
O’Callaghan JP, Sriram K (2005) Glial fibrillary acidic protein and related glial proteins as biomarkers of neurotoxicity. Expert Opin Drug Saf 4:433–442
Peretto P, Merighi A, Fasolo A, Bonfanti L (1997) Glial tubes in the rostral migratory stream of the adult rat. Brain Res Bull 42:9–21
Wang K, Bekar LK, Furber K, Walz W (2004) Vimentin-expressing proximal reactive astrocytes correlate with migration rather than proliferation following focal brain injury. Brain Res 1024:193–202
Herrmann JE, Imura T, Song B, Qi J, Ao Y, Nguyen TK, Korsak RA, Takeda K, Akira S, Sofroniew MV (2008) STAT3 is a critical regulator of astrogliosis and scar formation after spinal cord injury. J Neurosci 28:7231–7243
Zhu Z, Zhang Q, Yu Z, Zhang L, Tian D, Zhu S, Bu B, Xie M, Wang W (2007) Inhibiting cell cycle progression reduces reactive astrogliosis initiated by scratch injury in vitro and by cerebral ischemia in vivo. Glia 55:546–558
Araque A, Carmignoto G, Haydon PG (2001) Dynamic signaling between astrocytes and neurons. Annu Rev Physiol 63:795–813
Malhotra SK, Luong LT, Bhatnagar R, Shnitka TK (1997) Up-regulation of reactive astrogliosis in the rat glioma 9 L cell line by combined mechanical and chemical injuries. Cytobios 89(357):115–134
Wakasa S, Shiiya N, Tachibana T, Ooka T, Matsui Y (2009) A semiquantitative analysis of reactive astrogliosis demonstrates its correlation with the number of intact motor neurons after transient spinal cord ischemia. J Thorac Cardiovasc Surg 137(4):983–990
Okamoto M, Wang X, Baba M (2005) HIV-1-infected macrophages induce astrogliosis by SDF-1alpha and matrix metalloproteinases. Biochem Biophys Res Commun 336(4):1214–1220
Sofroniew MV (2009) Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci 32(12):638–647
El-Fawal HA, O’Callaghan JP (2008) Autoantibodies to neurotypic and gliotypic proteins as biomarkers of neurotoxicity: assessment of trimethyltin (TMT). Neurotoxicology 29(1):109–115
Norenberg MD, Rao KV, Jayakumar AR (2005) Mechanisms of ammonia-induced astrocyte swelling. Metab Brain Dis 20:303–318
Norton WT, Aquino DA, Hozumi I, Chiu FC, Brosnan CF (1992) Quantitative aspects of reactive gliosis: a review. Neurochem Res 17:877–885
Oppenheim RW, Houenou LJ, Parsadanian AS, Prevette D, Snider WD, Shen L (2000) Glial cell line-derived neurotrophic factor and developing mammalian motoneurons: regulation of programmed cell death among motoneuron subtypes. J Neurosci 20:5001–5011
Zhao Z, Alam S, Oppenheim RW, Prevette DM, Evenson A, Parsadanian A (2004) Overexpression of glial cell line-derived neurotrophic factor in the CNS rescues motoneurons from programmed cell death and promotes their long-term survival following axotomy. Exp Neurol 190:356–372
Struzynska L (2009) A glutamatergic component of lead toxicity in adult brain: the role of astrocytic glutamate transporters. Neurochem Int 55:151–156
Bush TG, Puvanachandra N, Horner CH, Polito A, Ostenfeld T, Svendsen CN, Mucke L, Johnson MH, Sofroniew MV (1999) Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice. Neuron 23:297–308
Faulkner JR, Herrmann JE, Woo MJ, Tansey KE, Doan NB, Sofroniew MV (2004) Reactive astrocytes protect tissue and preserve function after spinal cord injury. J Neurosci 24:2143–2155
Myer DJ, Gurkoff GG, Lee SM, Hovda DA, Sofroniew MV (2006) Essential protective roles of reactive astrocytes in traumatic brain injury. Brain 129:2761–2772
Weiss N, Miller F, Cazaubon S, Couraud PO (2009) The blood-brain barrier in brain homeostasis and neurological diseases. Biochim Biophys Acta 1788:842–857
Igarashi Y, Utsumi H, Chiba H, Yamada-Sasamori Y, Tobioka H, Kamimura Y, Furuuchi K, Kokai Y, Nakagawa T, Mori M, Sawada N (1999) Glial cell line-derived neurotrophic factor induces barrier function of endothelial cells forming the blood-brain barrier. Biochem Biophys Res Commun 261:108–112
Haseloff RF, Blasig IE, Bauer HC, Bauer H (2005) In search of the astrocytic factor(s) modulating blood-brain barrier functions in brain capillary endothelial cells in vitro. Cell Mol Neurobiol 25(1):25–39
Privat A (2003) Astrocytes as support for axonal regeneration in the central nervous system of mammals. Glia 43:91–93
Cafferty WB, Yang SH, Duffy PJ, Li S, Strittmatter SM (2007) Functional axonal regeneration through astrocytic scar genetically modified to digest chondroitin sulfate proteoglycans. J Neurosci 27:2176–2185
Rolls A, Shechter R, Schwartz M (2009) The bright side of the glial scar in CNS repair. Nat Rev Neurosci 10:235–241
Menet V, Prieto M, Privat A, Gimenez y Ribotta M (2003) Axonal plasticity and functional recovery after spinal cord injury in mice deficient in both glial fibrillary acidic protein and vimentin genes. Proc Natl Acad Sci USA 100:8999–9004
Wilhelmsson U, Li L, Pekna M, Berthold CH, Blom S, Eliasson C, Renner O, Bushong E, Ellisman M, Morgan TE, Pekny M (2004) Absence of glial fibrillary acidic protein and vimentin prevents hypertrophy of astrocytic processes and improves post-traumatic regeneration. J Neurosci 24:5016–5021
Oleszak EL, Zaczynska E, Bhattacharjee M, Butunoi C, Legido A, Katsetos CD (1998) Inducible nitric oxide synthase and nitrotyrosine are found in monocytes/macrophages and/or astrocytes in acute, but not in chronic, multiple sclerosis. Clin Diagn Lab Immunol 5:438–445
Estevez AG, Spear N, Manuel SM, Radi R, Henderson CE, Barbeito L, Beckman JS (1998) Nitric oxide and superoxide contribute to motor neuron apoptosis induced by trophic factor deprivation. J Neurosci 18:923–931
Bezzi P, Domercq M, Brambilla L, Galli R, Schols D, De Clercq E, Vescovi A, Bagetta G, Kollias G, Meldolesi J, Volterra A (2001) CXCR4-activated astrocyte glutamate release via TNFalpha: amplification by microglia triggers neurotoxicity. Nat Neurosci 4:702–710
Chauhan VS, Sterka DG Jr, Gray DL, Bost KL, Marriott I (2008) Neurogenic exacerbation of microglial and astrocyte responses to Neisseria meningitidis and Borrelia burgdorferi. J Immunol 180:8241–8249
Khurgel M, Ivy GO (1996) Astrocytes in kindling: relevance to epileptogenesis. Epilepsy Res 26:163–175
Miyazaki T, Miyamoto O, Janjua NA, Hata T, Takahashi F, Itano T (2003) Reactive gliosis in areas around third ventricle in association with epileptogenesis in amygdaloid-kindled rat. Epilepsy Res 56:5–15
Lycke JN, Karlsson JE, Andersen O, Rosengren LE (1998) Neurofilament protein in cerebrospinal fluid: a potential marker of activity in multiple sclerosis. J Neurol Neurosurg Psychiatry 64:402–404
Canton T, Pratt J, Stutzmann JM, Imperato A, Boireau A (1998) Glutamate uptake is decreased tardively in the spinal cord of FALS mice. NeuroReport 9:775–778
Ferri A, Nencini M, Casciati A, Cozzolino M, Angelini DF, Longone P, Spalloni A, Rotilio G, Carri MT (2004) Cell death in amyotrophic lateral sclerosis: interplay between neuronal and glial cells. Faseb J 18:1261–1263
Sabri F, Titanji K, De Milito A, Chiodi F (2003) Astrocyte activation and apoptosis: their roles in the neuropathology of HIV infection. Brain Pathol 13:84–94
Sporer B, Missler U, Magerkurth O, Koedel U, Wiesmann M, Pfister HW (2004) Evaluation of CSF glial fibrillary acidic protein (GFAP) as a putative marker for HIV-associated dementia. Infection 32:20–23
Hayakawa T, Ushio Y, Mori T, Arita N, Yoshimine T, Maeda Y, Shimizu K, Myoga A (1979) Levels in stroke patients of CSF astroprotein, an astrocyte-specific cerebroprotein. Stroke 10:685–689
Kernie SG, Erwin TM, Parada LF (2001) Brain remodeling due to neuronal and astrocytic proliferation after controlled cortical injury in mice. J Neurosci Res 66:317–326
Fitch MT, Silver J (1997) Glial cell extracellular matrix: boundaries for axon growth in development and regeneration. Cell Tissue Res 290:379–384
Rock RB, Gekker G, Hu S, Sheng WS, Cheeran M, Lokensgard JR, Peterson PK (2004) Role of microglia in central nervous system infections. Clin Microbiol Rev 17:942–964, table of contents
Neumann H, Kotter MR, Franklin RJ (2009) Debris clearance by microglia: an essential link between degeneration and regeneration. Brain 132:288–295
Polazzi E, Levi G, Minghetti L (1999) Human immunodeficiency virus type 1 Tat protein stimulates inducible nitric oxide synthase expression and nitric oxide production in microglial cultures. J Neuropathol Exp Neurol 58(8):825–831
Liu B, Jiang JW, Wilson BC, Du L, Yang SN, Wang JY, Wu GC, Cao XD, Hong JS (2000) Systemic infusion of naloxone reduces degeneration of rat substantia nigral dopaminergic neurons induced by intranigral injection of lipopolysaccharide. J Pharmacol Exp Ther 295(1):125–132
Teeling JL, Perry VH (2009) Systemic infection and inflammation in acute CNS injury and chronic neurodegeneration: underlying mechanisms. Neuroscience 158(3):1062–1073
Hanisch UK, Kettenmann H (2007) Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 10:1387–1394
Block ML, Hong JS (2005) Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Prog Neurobiol 76:77–98
Rohl C, Lucius R, Sievers J (2007) The effect of activated microglia on astrogliosis parameters in astrocyte cultures. Brain Res 1129:43–52
Cernak I, Stoica B, Byrnes KR, Di Giovanni S, Faden AI (2005) Role of the cell cycle in the pathobiology of central nervous system trauma. Cell Cycle 4:1286–1293
Gunther A, Kuppers-Tiedt L, Schneider PM, Kunert I, Berrouschot J, Schneider D, Rossner S (2005) Reduced infarct volume and differential effects on glial cell activation after hyperbaric oxygen treatment in rat permanent focal cerebral ischaemia. Eur J NeuroSci 21:3189–3194
Miller JM, McAllister JP (2007) Reduction of astrogliosis and microgliosis by cerebrospinal fluid shunting in experimental hydrocephalus. Cerebrospinal Fluid Res 4:5
Block ML, Zecca L, Hong JS (2007) Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 8:57–69
Hu X, Zhang D, Pang H, Caudle WM, Li Y, Gao H, Liu Y, Qian L, Wilson B, Di Monte DA, Ali SF, Zhang J, Block ML, Hong JS (2008) Macrophage antigen complex-1 mediates reactive microgliosis and progressive dopaminergic neurodegeneration in the MPTP model of Parkinson’s disease. J Immunol 181:7194–7204
Kreutzberg GW (1996) Microglia: a sensor for pathological events in the CNS. Trends Neurosci 19:312–318
Gonzalez-Scarano F, Baltuch G (1999) Microglia as mediators of inflammatory and degenerative diseases. Annu Rev Neurosci 22:219–240
Nguyen VT, Benveniste EN (2002) Critical role of tumor necrosis factor-alpha and NF-kappa B in interferon-gamma -induced CD40 expression in microglia/macrophages. J Biol Chem 277:13796–13803
Gehrmann J (1996) Microglia: a sensor to threats in the nervous system? Res Virol 147:79–88
Zhang D, Hu X, Qian L, Wilson B, Lee C, Flood P, Langenbach R, Hong JS (2009) Prostaglandin E2 released from activated microglia enhances astrocyte proliferation in vitro. Toxicol Appl Pharmacol 238:64–70
Schmitt AB, Brook GA, Buss A, Nacimiento W, Noth J, Kreutzberg GW (1998) Dynamics of microglial activation in the spinal cord after cerebral infarction are revealed by expression of MHC class II antigen. Neuropathol Appl Neurobiol 24:167–176
v Eitzen U, Egensperger R, Kösel S, Grasbon-Frodl EM, Imai Y, Bise K, Kohsaka S, Mehraein P, Graeber MB (1998) Microglia and the development of spongiform change in Creutzfeldt-Jakob disease. J Neuropathol Exp Neurol 57(3):246–56
Graeber MB, Kreutzberg GW (1988) Delayed astrocyte reaction following facial nerve axotomy. J Neurocytol 17:209–220
Gehrmann J, Schoen SW, Kreutzberg GW (1991) Lesion of the rat entorhinal cortex leads to a rapid microglial reaction in the dentate gyrus. A light and electron microscopical study. Acta Neuropathol 82:442–455
Dusart I, Schwab ME (1994) Secondary cell death and the inflammatory reaction after dorsal hemisection of the rat spinal cord. Eur J NeuroSci 6:712–724
Frank M, Wolburg H (1996) Cellular reactions at the lesion site after crushing of the rat optic nerve. Glia 16:227–240
Liberatore GT, Jackson-Lewis V, Vukosavic S, Mandir AS, Vila M, McAuliffe WG, Dawson VL, Dawson TM, Przedborski S (1999) Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease. Nat Med 5:1403–1409
McCann MJ, O’Callaghan JP, Martin PM, Bertram T, Streit WJ (1996) Differential activation of microglia and astrocytes following trimethyl tin-induced neurodegeneration. Neuroscience 72:273–281
Murphy M, Dutton R, Koblar S, Cheema S, Bartlett P (1997) Cytokines which signal through the LIF receptor and their actions in the nervous system. Prog Neurobiol 52:355–378
Hanisch UK (2002) Microglia as a source and target of cytokines. Glia 40:140–155
Beattie MS (2004) Inflammation and apoptosis: linked therapeutic targets in spinal cord injury. Trends Mol Med 10:580–583
Norris JG, Tang LP, Sparacio SM, Benveniste EN (1994) Signal transduction pathways mediating astrocyte IL-6 induction by IL-1 beta and tumor necrosis factor-alpha. J Immunol 152:841–850
Nakamura M, Okada S, Toyama Y, Okano H (2005) Role of IL-6 in spinal cord injury in a mouse model. Clin Rev Allergy Immunol 28:197–204
Lacy M, Jones J, Whittemore SR, Haviland DL, Wetsel RA, Barnum SR (1995) Expression of the receptors for the C5a anaphylatoxin, interleukin-8 and FMLP by human astrocytes and microglia. J Neuroimmunol 61:71–78
Dorf ME, Berman MA, Tanabe S, Heesen M, Luo Y (2000) Astrocytes express functional chemokine receptors. J Neuroimmunol 111:109–121
Sawada M, Itoh Y, Suzumura A, Marunouchi T (1993) Expression of cytokine receptors in cultured neuronal and glial cells. Neurosci Lett 160:131–134
Benveniste EN, Benos DJ (1995) TNF-alpha- and IFN-gamma-mediated signal transduction pathways: effects on glial cell gene expression and function. Faseb J 9:1577–1584
Pickering M, Cumiskey D, O’Connor JJ (2005) Actions of TNF-alpha on glutamatergic synaptic transmission in the central nervous system. Exp Physiol 90:663–670
Barna BP, Estes ML, Jacobs BS, Hudson S, Ransohoff RM (1990) Human astrocytes proliferate in response to tumor necrosis factor alpha. J Neuroimmunol 30:239–243
Cardenas H, Bolin LM (2003) Compromised reactive microgliosis in MPTP-lesioned IL-6 KO mice. Brain Res 985:89–97
Herx LM, Yong VW (2001) Interleukin-1 beta is required for the early evolution of reactive astrogliosis following CNS lesion. J Neuropathol Exp Neurol 60:961–971
Mohri I, Taniike M, Taniguchi H, Kanekiyo T, Aritake K, Inui T, Fukumoto N, Eguchi N, Kushi A, Sasai H, Kanaoka Y, Ozono K, Narumiya S, Suzuki K, Urade Y (2006) Prostaglandin D2-mediated microglia/astrocyte interaction enhances astrogliosis and demyelination in twitcher. J Neurosci 26:4383–4393
Selmaj KW, Farooq M, Norton WT, Raine CS, Brosnan CF (1990) Proliferation of astrocytes in vitro in response to cytokines. A primary role for tumor necrosis factor. J Immunol 144:129–135
Balasingam V, Tejada-Berges T, Wright E, Bouckova R, Yong VW (1994) Reactive astrogliosis in the neonatal mouse brain and its modulation by cytokines. J Neurosci 14:846–856
Giulian D, Woodward J, Young DG, Krebs JF, Lachman LB (1988) Interleukin-1 injected into mammalian brain stimulates astrogliosis and neovascularization. J Neurosci 8:2485–2490
Herx LM, Rivest S, Yong VW (2000) Central nervous system-initiated inflammation and neurotrophism in trauma: IL-1 beta is required for the production of ciliary neurotrophic factor. J Immunol 165:2232–2239
Sriram K, Miller DB, O’Callaghan JP (2006) Minocycline attenuates microglial activation but fails to mitigate striatal dopaminergic neurotoxicity: role of tumor necrosis factor-alpha. J Neurochem 96:706–718
von Boyen GB, Steinkamp M, Reinshagen M, Schafer KH, Adler G, Kirsch J (2004) Proinflammatory cytokines increase glial fibrillary acidic protein expression in enteric glia. Gut 53:222–228
Lotan M, Schwartz M (1994) Cross talk between the immune system and the nervous system in response to injury: implications for regeneration. Faseb J 8:1026–1033
Raghavendra V, Tanga F, DeLeo JA (2003) Inhibition of microglial activation attenuates the development but not existing hypersensitivity in a rat model of neuropathy. J Pharmacol Exp Ther 306:624–630
Leonardo CC, Eakin AK, Ajmo JM, Collier LA, Pennypacker KR, Strongin AY, Gottschall PE (2008) Delayed administration of a matrix metalloproteinase inhibitor limits progressive brain injury after hypoxia-ischemia in the neonatal rat. J Neuroinflammation 5:34
Raivich G, Moreno-Flores MT, Moller JC, Kreutzberg GW (1994) Inhibition of posttraumatic microglial proliferation in a genetic model of macrophage colony-stimulating factor deficiency in the mouse. Eur J NeuroSci 6:1615–1618
Tian DS, Dong Q, Pan DJ, He Y, Yu ZY, Xie MJ, Wang W (2007) Attenuation of astrogliosis by suppressing of microglial proliferation with the cell cycle inhibitor olomoucine in rat spinal cord injury model. Brain Res 1154:206–214
Spataro L, Dilgen J, Retterer S, Spence AJ, Isaacson M, Turner JN, Shain W (2005) Dexamethasone treatment reduces astroglia responses to inserted neuroprosthetic devices in rat neocortex. Exp Neurol 194:289–300
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zhang, D., Hu, X., Qian, L. et al. Astrogliosis in CNS Pathologies: Is There A Role for Microglia?. Mol Neurobiol 41, 232–241 (2010). https://doi.org/10.1007/s12035-010-8098-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12035-010-8098-4