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Acta Neuropathologica
Published in: Acta Neuropathologica 1/2010

Open Access 01-01-2010 | Review

Astrocytes: biology and pathology

Authors: Michael V. Sofroniew, Harry V. Vinters

Published in: Acta Neuropathologica | Issue 1/2010

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Abstract

Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions.
Literature
1.
Abbott NJ, Ronnback L, Hansson E (2006) Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci 7:41–53PubMed
2.
Acosta MT, Gioia GA, Silva AJ (2006) Neurofibromatosis type 1: new insights into neurocognitive issues. Curr Neurol Neurosci Rep 6:136–143PubMed
3.
Akaoka H, Szymocha R, Beurton-Marduel P, Bernard A, Belin MF, Giraudon P (2001) Functional changes in astrocytes by human T-lymphotropic virus type-1 T-lymphocytes. Virus Res 78:57–66PubMed
4.
Andreiuolo F, Junier MP, Hol EM, Miquel C, Chimelli L, Leonard N, Chneiweiss H, Daumas-Duport C, Varlet P (2009) GFAPdelta immunostaining improves visualization of normal and pathologic astrocytic heterogeneity. Neuropathology 29:31–39PubMed
5.
Araque A, Parpura V, Sanzgiri RP, Haydon PG (1999) Tripartite synapses: glia, the unacknowledged partner. Trends Neurosci 22:208–215PubMed
6.
Araya R, Kudo M, Kawano M, Ishii K, Hashikawa T, Iwasato T, Itohara S, Terasaki T, Oohira A, Mishina Y, Yamada M (2008) BMP signaling through BMPRIA in astrocytes is essential for proper cerebral angiogenesis and formation of the blood-brain-barrier. Mol Cell Neurosci 38:417–430PubMed
7.
Argaw AT, Gurfein BT, Zhang Y, Zameer A, John GR (2009) VEGF-mediated disruption of endothelial CLN-5 promotes blood-brain barrier breakdown. Proc Natl Acad Sci USA 106:1977–1982PubMed
8.
Armah HB, Wang G, Omalu BI, Tesh RB, Gyure KA, Chute DJ, Smith RD, Dulai P, Vinters HV, Kleinschmidt-DeMasters BK, Wiley CA (2007) Systemic distribution of West Nile virus infection: postmortem immunohistochemical study of six cases. Brain Pathol 17:354–362PubMed
9.
Arun D, Gutmann DH (2004) Recent advances in neurofibromatosis type 1. Curr Opin Neurol 17:101–105PubMed
10.
Bachoo RM, Kim RS, Ligon KL, Maher EA, Brennan C, Billings N, Chan S, Li C, Rowitch DH, Wong WH, DePinho RA (2004) Molecular diversity of astrocytes with implications for neurological disorders. Proc Natl Acad Sci USA 101:8384–8389PubMed
11.
Ballabh P, Braun A, Nedergaard M (2004) The blood-brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol Dis 16:1–13PubMed
12.
Barcia C, Sanderson NS, Barrett RJ, Wawrowsky K, Kroeger KM, Puntel M, Liu C, Castro MG, Lowenstein PR (2008) T cells’ immunological synapses induce polarization of brain astrocytes in vivo and in vitro: a novel astrocyte response mechanism to cellular injury. PLoS One 3:e2977PubMed
13.
Barcia C, Thomas CE, Curtin JF, King GD, Wawrowsky K, Candolfi M, Xiong WD, Liu C, Kroeger K, Boyer O, Kupiec-Weglinski J, Klatzmann D, Castro MG, Lowenstein PR (2006) In vivo mature immunological synapses forming SMACs mediate clearance of virally infected astrocytes from the brain. J Exp Med 203:2095–2107PubMed
14.
15.
Barres BA (2008) The mystery and magic of glia: a perspective on their roles in health and disease. Neuron 60:430–440PubMed
16.
Bauer J, Elger CE, Hans VH, Schramm J, Urbach H, Lassmann H, Bien CG (2007) Astrocytes are a specific immunological target in Rasmussen’s encephalitis. Ann Neurol 62:67–80PubMed
17.
Beck DW, Vinters HV, Hart MN, Cancilla PA (1984) Glial cells influence polarity of the blood-brain barrier. J Neuropathol Exp Neurol 43:219–224PubMed
18.
Behrstock S, Ebert AD, Klein S, Schmitt M, Moore JM, Svendsen CN (2008) Lesion-induced increase in survival and migration of human neural progenitor cells releasing GDNF. Cell Transplant 17:753–762PubMed
19.
Bernstein HG, Steiner J, Bogerts B (2009) Glial cells in schizophrenia: pathophysiological significance and possible consequences for therapy. Expert Rev Neurother 9:1059–1071PubMed
20.
Blechingberg J, Holm IE, Nielsen KB, Jensen TH, Jorgensen AL, Nielsen AL (2007) Identification and characterization of GFAPkappa, a novel glial fibrillary acidic protein isoform. Glia 55:497–507PubMed
21.
Boor PK, de Groot K, Waisfisz Q, Kamphorst W, Oudejans CB, Powers JM, Pronk JC, Scheper GC, van der Knaap MS (2005) MLC1: a novel protein in distal astroglial processes. J Neuropathol Exp Neurol 64:412–419PubMed
22.
Brambilla R, Bracchi-Ricard V, Hu WH, Frydel B, Bramwell A, Karmally S, Green EJ, Bethea JR (2005) Inhibition of astroglial nuclear factor kappaB reduces inflammation and improves functional recovery after spinal cord injury. J Exp Med 202:145–156PubMed
23.
Brambilla R, Persaud T, Hu X, Karmally S, Shestopalov VI, Dvoriantchikova G, Ivanov D, Nathanson L, Barnum SR, Bethea JR (2009) Transgenic inhibition of astroglial NF-kappaB improves functional outcome in experimental autoimmune encephalomyelitis by suppressing chronic central nervous system inflammation. J Immunol 182:2628–2640PubMed
24.
Brantley EC, Nabors LB, Gillespie GY, Choi YH, Palmer CA, Harrison K, Roarty K, Benveniste EN (2008) Loss of protein inhibitors of activated STAT-3 expression in glioblastoma multiforme tumors: implications for STAT-3 activation and gene expression. Clin Cancer Res 14:4694–4704PubMed
25.
Brenner M, Johnson AB, Boespflug-Tanguy O, Rodriguez D, Goldman JE, Messing A (2001) Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease. Nat Genet 27:117–120PubMed
26.
Bringmann A, Pannicke T, Grosche J, Francke M, Wiedemann P, Skatchkov SN, Osborne NN, Reichenbach A (2006) Muller cells in the healthy and diseased retina. Prog Retin Eye Res 25:397–424PubMed
27.
Brown AM, Ransom BR (2007) Astrocyte glycogen and brain energy metabolism. Glia 55:1263–1271PubMed
28.
Brown AM, Baltan Tekkok S, Ransom BR (2004) Energy transfer from astrocytes to axons: the role of CNS glycogen. Neurochem Int 45:529–536PubMed
29.
Buffo A, Vosko MR, Erturk D, Hamann GF, Jucker M, Rowitch D, Gotz M (2005) Expression pattern of the transcription factor Olig2 in response to brain injuries: implications for neuronal repair. Proc Natl Acad Sci USA 102:18183–18188PubMed
30.
Buffo A, Rite I, Tripathi P, Lepier A, Colak D, Horn AP, Mori T, Gotz M (2008) Origin and progeny of reactive gliosis: A source of multipotent cells in the injured brain. Proc Natl Acad Sci USA 105:3581–3586PubMed
31.
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 23:7789–7800PubMed
32.
Bush TG, Savidge TC, Freeman TC, Cox HJ, Campbell EA, Mucke L, Johnson MH, Sofroniew MV (1998) Fulminant jejuno-ileitis following ablation of enteric glia in adult transgenic mice. Cell 93:189–201PubMed
33.
Bush TG NP, 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 23:297–308PubMed
34.
Bushong EA, Martone MA, Jones YZ, Ellisman MH (2002) Protoplasmic astrocytes in CA1 atratum radiatum occupy separate anatomical domains. J Neurosci 22:183–192PubMed
35.
Cahoy JD, Emery B, Kaushal A, Foo LC, Zamanian JL, Christopherson KS, Xing Y, Lubischer JL, Krieg PA, Krupenko SA, Thompson WJ, Barres BA (2008) A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. J Neurosci 28:264–278PubMed
36.
Capendeguy O, Horisberger JD (2004) Functional effects of Na + , K + -ATPase gene mutations linked to familial hemiplegic migraine. Neuromolecular Med 6:105–116PubMed
37.
Carlen M, Meletis K, Goritz C, Darsalia V, Evergren E, Tanigaki K, Amendola M, Barnabe-Heider F, Yeung MS, Naldini L, Honjo T, Kokaia Z, Shupliakov O, Cassidy RM, Lindvall O, Frisen J (2009) Forebrain ependymal cells are Notch-dependent and generate neuroblasts and astrocytes after stroke. Nat Neurosci 12:259–267PubMed
38.
Carmichael ST (2006) Cellular and molecular mechanisms of neural repair after stroke: making waves. Ann Neurol 59:735–742PubMed
39.
Charles AC, Merrill JE, Dirksen ER, Sanderson MJ (1991) Intercellular signaling in glial cells: calcium waves and oscillations in response to mechanical stimulation and glutamate. Neuron 6:983–992PubMed
40.
Chen PC, Vargas MR, Pani AK, Smeyne RJ, Johnson DA, Kan YW, Johnson JA (2009) Nrf2-mediated neuroprotection in the MPTP mouse model of Parkinson’s disease: Critical role for the astrocyte. Proc Natl Acad Sci USA 106:2933–2938PubMed
41.
Chen Y, Swanson RA (2003) Astrocytes and brain injury. J Cereb Blood Flow Metab 23:137–149PubMed
42.
Chen Y, Vartiainen NE, Ying W, Chan PH, Koistinaho J, Swanson RA (2001) Astrocytes protect neurons from nitric oxide toxicity by a glutathione-dependent mechanism. J Neurochem 77:1601–1610PubMed
43.
Christopherson KS, Ullian EM, Stokes CC, Mullowney CE, Hell JW, Agah A, Lawler J, Mosher DF, Bornstein P, Barres BA (2005) Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis. Cell 120:421–433PubMed
44.
Cirillo C, Sarnelli G, Esposito G, Grosso M, Petruzzelli R, Izzo P, Cali G, D’Armiento FP, Rocco A, Nardone G, Iuvone T, Steardo L, Cuomo R (2009) Increased mucosal nitric oxide production in ulcerative colitis is mediated in part by the enteroglial-derived S100B protein. Neurogastroenterol Motil 21:1209–1212PubMed
45.
Colodner KJ, Montana RA, Anthony DC, Folkerth RD, De Girolami U, Feany MB (2005) Proliferative potential of human astrocytes. J Neuropathol Exp Neurol 64:163–169PubMed
46.
Cornell-Bell AH, Finkbeiner SM, Cooper MS, Smith SJ (1990) Glutamate induces calcium waves in cultured astrocytes: long-range glial signaling. Science 247:470–473PubMed
47.
Crino PB, Miyata H, Vinters HV (2002) Neurodevelopmental disorders as a cause of seizures: neuropathologic, genetic, and mechanistic considerations. Brain Pathol 12:212–233PubMed
48.
Dabir DV, Robinson MB, Swanson E, Zhang B, Trojanowski JQ, Lee VM, Forman MS (2006) Impaired glutamate transport in a mouse model of tau pathology in astrocytes. J Neurosci 26:644–654PubMed
49.
Daneman R, Rescigno M (2009) The gut immune barrier and the blood-brain barrier: are they so different? Immunity (Epub 20 October 2009)
50.
Dasgupta B, Yi Y, Chen DY, Weber JD, Gutmann DH (2005) Proteomic analysis reveals hyperactivation of the mammalian target of rapamycin pathway in neurofibromatosis 1-associated human and mouse brain tumors. Cancer Res 65:2755–2760PubMed
51.
David Y, Cacheaux LP, Ivens S, Lapilover E, Heinemann U, Kaufer D, Friedman A (2009) Astrocytic dysfunction in epileptogenesis: consequence of altered potassium and glutamate homeostasis? J Neurosci 29:10588–10599PubMed
52.
De Keyser J, Mostert JP, Koch MW (2008) Dysfunctional astrocytes as key players in the pathogenesis of central nervous system disorders. J Neurol Sci 267:3–16PubMed
53.
Di Giorgio FP, Carrasco MA, Siao MC, Maniatis T, Eggan K (2007) Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model. Nat Neurosci 10:608–614PubMed
54.
Di Monte DA, Royland JE, Irwin I, Langston JW (1996) Astrocytes as the site for bioactivation of neurotoxins. Neurotoxicology 17:697–703PubMed
55.
Dietrich J, Lacagnina M, Gass D, Richfield E, Mayer-Proschel M, Noble M, Torres C, Proschel C (2005) EIF2B5 mutations compromise GFAP + astrocyte generation in vanishing white matter leukodystrophy. Nat Med 11:277–283PubMed
56.
Doetsch F, Caille I, Lim DA, Garcia-Verdugo JM, Alvarez-Buylla A (1999) Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97:703–716PubMed
57.
Donati D, Martinelli E, Cassiani-Ingoni R, Ahlqvist J, Hou J, Major EO, Jacobson S (2005) Variant-specific tropism of human herpesvirus 6 in human astrocytes. J Virol 79:9439–9448PubMed
58.
Dong Y, Benveniste EN (2001) Immune function of astrocytes. Glia 36:180–190PubMed
59.
Drogemuller K, Helmuth U, Brunn A, Sakowicz-Burkiewicz M, Gutmann DH, Mueller W, Deckert M, Schluter D (2008) Astrocyte gp130 expression is critical for the control of Toxoplasma encephalitis. J Immunol 181:2683–2693PubMed
60.
Eddleston M, Mucke L (1993) Molecular profile of reactive astrocytes—implications for their role in neurological disease. Neuroscience 54:15–36PubMed
61.
Eid T, Lee TS, Thomas MJ, Amiry-Moghaddam M, Bjornsen LP, Spencer DD, Agre P, Ottersen OP, de Lanerolle NC (2005) Loss of perivascular aquaporin 4 may underlie deficient water and K + homeostasis in the human epileptogenic hippocampus. Proc Natl Acad Sci USA 102:1193–1198PubMed
62.
Eng LF, Gerstl B, Vanderhaeghen JJ (1970) A study of proteins in old multiple sclerosis plaques. Trans Am Soc Neurochem 1:42
63.
Eng LF, Ghirnikar RS, Lee YL (2000) Glial fibrillary acidic protein: GFAP-thirty-one years (1969–2000). Neurochem Res 25:1439–1451PubMed
64.
65.
Erana-Rojas IE, Barboza-Quintana A, Ayala AG, Fuller GN (2002) Demyelinating pseudotumor. Ann Diagn Pathol 6:265–271PubMed
66.
Escartin C, Bonvento G (2008) Targeted activation of astrocytes: a potential neuroprotective strategy. Mol Neurobiol 38:231–241PubMed
67.
Farina C, Aloisi F, Meinl E (2007) Astrocytes are active players in cerebral innate immunity. Trends Immunol 28:138–145PubMed
68.
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 24:2143–2155PubMed
69.
Fisher M (2008) Injuries to the vascular endothelium: vascular wall and endothelial dysfunction. Rev Neurol Dis 5(Suppl 1):S4–S11
70.
Fontana AC, de Oliveira Beleboni R, Wojewodzic MW, Ferreira Dos Santos W, Coutinho-Netto J, Grutle NJ, Watts SD, Danbolt NC, Amara SG (2007) Enhancing glutamate transport: mechanism of action of Parawixin1, a neuroprotective compound from Parawixia bistriata spider venom. Mol Pharmacol 72:1228–1237PubMed
71.
Forman MS, Lal D, Zhang B, Dabir DV, Swanson E, Lee VM, Trojanowski JQ (2005) Transgenic mouse model of tau pathology in astrocytes leading to nervous system degeneration. J Neurosci 25:3539–3550PubMed
72.
Forno LS, DeLanney LE, Irwin I, Di Monte D, Langston JW (1992) Astrocytes and Parkinson’s disease. Prog Brain Res 94:429–436PubMed
73.
Fray AE, Ince PG, Banner SJ, Milton ID, Usher PA, Cookson MR, Shaw PJ (1998) The expression of the glial glutamate transporter protein EAAT2 in motor neuron disease: an immunohistochemical study. Eur J Neurosci 10:2481–2489PubMed
74.
Friedman A, Kaufer D, Heinemann U (2009) Blood-brain barrier breakdown-inducing astrocytic transformation: novel targets for the prevention of epilepsy. Epilepsy Res 85:142–149PubMed
75.
Furer M, Hartloper V, Wilkins J, Nath A (1993) Lymphocyte emperipolesis in human glial cells. Cell Adhes Commun 1:223–237PubMed
76.
Furnari FB, Fenton T, Bachoo RM, Mukasa A, Stommel JM, Stegh A, Hahn WC, Ligon KL, Louis DN, Brennan C, Chin L, DePinho RA, Cavenee WK (2007) Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev 21:2683–2710PubMed
77.
Gadea A, Schinelli S, Gallo V (2008) Endothelin-1 regulates astrocyte proliferation and reactive gliosis via a JNK/c-Jun signaling pathway. J Neurosci 28:2394–2408PubMed
78.
Garcia ADR, Doan NB, Imura T, Bush TG, Sofroniew MV (2004) GFAP-expressing progenitors are the principle source of constitutive neurogenesis in adult mouse forebrain. Nature Neurosci 7:1233–1241PubMed
79.
Garcia-Cazorla A, Rabier D, Touati G, Chadefaux-Vekemans B, Marsac C, de Lonlay P, Saudubray JM (2006) Pyruvate carboxylase deficiency: metabolic characteristics and new neurological aspects. Ann Neurol 59:121–127PubMed
80.
Garcia-Segura LM, Melcangi RC (2006) Steroids and glial cell function. Glia 54:485–498PubMed
81.
Ghatak NR (1992) Occurrence of oligodendrocytes within astrocytes in demyelinating lesions. J Neuropathol Exp Neurol 51:40–46PubMed
82.
Gil JM, Rego AC (2008) Mechanisms of neurodegeneration in Huntington’s disease. Eur J Neurosci 27:2803–2820PubMed
83.
Goedert M, Jakes R (2005) Mutations causing neurodegenerative tauopathies. Biochim Biophys Acta 1739:240–250PubMed
84.
Goldman S (2003) Glia as neural progenitor cells. Trends Neurosci 26:590–596PubMed
85.
Goncalves CA, Leite MC, Nardin P (2008) Biological and methodological features of the measurement of S100B, a putative marker of brain injury. Clin Biochem 41:755–763PubMed
86.
Gordon GR, Mulligan SJ, MacVicar BA (2007) Astrocyte control of the cerebrovasculature. Glia 55:1214–1221PubMed
87.
Gregorian C, Nakashima J, Dry SM, Nghiemphu PL, Smith KB, Ao Y, Dang J, Lawson G, Mellinghoff IK, Mischel PS, Phelps M, Parada LF, Liu X, Sofroniew MV, Eiber FC, Wu H (2009) PTEN dosage is essential for neurofibroma development and malignant transformation. Proc Natl Acad Sci USA 106:19479–19484
88.
Haberle J, Gorg B, Rutsch F, Schmidt E, Toutain A, Benoist JF, Gelot A, Suc AL, Hohne W, Schliess F, Haussinger D, Koch HG (2005) Congenital glutamine deficiency with glutamine synthetase mutations. N Engl J Med 353:1926–1933PubMed
89.
Halassa MM, Fellin T, Haydon PG (2007) The tripartite synapse: roles for gliotransmission in health and disease. Trends Mol Med 13:54–63PubMed
90.
Halassa MM, Fellin T, Haydon PG (2009) Tripartite synapses: roles for astrocytic purines in the control of synaptic physiology and behavior. Neuropharmacology 57:343–346PubMed
91.
Halassa MM, Fellin T, Takano H, Dong JH, Haydon PG (2007) Synaptic islands defined by the territory of a single astrocyte. J Neurosci 27:6473–6477PubMed
92.
Hamby ME, Hewett JA, Hewett SJ (2006) TGF-beta1 potentiates astrocytic nitric oxide production by expanding the population of astrocytes that express NOS-2. Glia 54:566–577PubMed
93.
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 25:25–39PubMed
94.
Hernandez MR, Miao H, Lukas T (2008) Astrocytes in glaucomatous optic neuropathy. Prog Brain Res 173:353–373PubMed
95.
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 28:7231–7243PubMed
96.
Hewett JA (2009) Determinants of regional and local diversity within the astroglial lineage of the normal central nervous system. J Neurochem 110:1717–1736PubMed
97.
Horner PJ, Power AE, Kempermann G, Kuhn HG, Palmer TD, Winkler J, Thal LJ, Gage FH (2000) Proliferation and differentiation of progenitor cells throughout the intact adult rat spinal cord. J Neurosci 20:2218–2228PubMed
98.
Howell GR, Libby RT, Jakobs TC, Smith RS, Phalan FC, Barter JW, Barbay JM, Marchant JK, Mahesh N, Porciatti V, Whitmore AV, Masland RH, John SW (2007) Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2 J glaucoma. J Cell Biol 179:1523–1537PubMed
99.
Huang TT, Sarkaria SM, Cloughesy TF, Mischel PS (2009) Targeted therapy for malignant glioma patients: lessons learned and the road ahead. Neurotherapeutics 6:500–512PubMed
100.
Hult B, Chana G, Masliah E, Everall I (2008) Neurobiology of HIV. Int Rev Psychiatry 20:3–13PubMed
101.
Huynh DP, Vinters HV, Ho DH, Ho VV, Pulst SM (1997) Neuronal expression and intracellular localization of presenilins in normal and Alzheimer disease brains. J Neuropathol Exp Neurol 56:1009–1017PubMed
102.
Iadecola C, Nedergaard M (2007) Glial regulation of the cerebral microvasculature. Nat Neurosci 10:1369–1376PubMed
103.
Imura T, Kornblum HI, Sofroniew MV (2003) The predominant neural stem cell isolated from postnatal and adult forebrain but not from early embryonic forebrain expresses GFAP. J Neurosci 23:2824–2832PubMed
104.
Imura T, Nakano I, Kornblum HI, Sofroniew MV (2006) Phenotypic and functional heterogeneity of GFAP-expressing cells in vitro: Differential expression of LeX/CD15 by GFAP-expressing multipotent neural stem cells and non-neurogenic astrocytes. Glia 53:277–293PubMed
105.
Jacob A, Hensley LK, Safratowich BD, Quigg RJ, Alexander JJ (2007) The role of the complement cascade in endotoxin-induced septic encephalopathy. Lab Invest 87:1186–1194PubMed
106.
Jansen LA, Uhlmann EJ, Crino PB, Gutmann DH, Wong M (2005) Epileptogenesis and reduced inward rectifier potassium current in tuberous sclerosis complex-1-deficient astrocytes. Epilepsia 46:1871–1880PubMed
107.
Jayakumar AR, Rama Rao KV, Tong XY, Norenberg MD (2009) Calcium in the mechanism of ammonia-induced astrocyte swelling. J Neurochem 109(Suppl 1):252–257
108.
John GR, Lee SC, Brosnan CF (2003) Cytokines: Powerful regulators of glial cell activation. Neuroscientist 9:10–22PubMed
109.
Johnson EC, Morrison JC (2009) Friend or foe? Resolving the impact of glial responses in glaucoma. J Glaucoma 18:341–353PubMed
110.
Kapur R, Donohue C, Jelinek D, Erickson RP (2009) Amelioration of enteric neuropathology in a mouse model of Niemann-Pick C by Npc1 expression in enteric glia. J Neurosci Res 87:2994–3001PubMed
111.
Khanlou N, Mathern GW, Mitchell WG, Salamon N, Pope WB, Yong WH, Vinters HV (2009) Cortical dysplasia with prominent Rosenthal fiber formation in a case of intractable pediatric epilepsy. Hum Pathol 40:1200–1204PubMed
112.
Koehler RC, Roman RJ, Harder DR (2009) Astrocytes and the regulation of cerebral blood flow. Trends Neurosci 32:160–169PubMed
113.
Koistinaho M, Lin S, Wu X, Esterman M, Koger D, Hanson J, Higgs R, Liu F, Malkani S, Bales KR, Paul SM (2004) Apolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-beta peptides. Nat Med 10:719–726PubMed
114.
Kostianovsky AM, Maier LM, Anderson RC, Bruce JN, Anderson DE (2008) Astrocytic regulation of human monocytic/microglial activation. J Immunol 181:5425–5432PubMed
115.
Kovacs GG, Budka H (2008) Prion diseases: from protein to cell pathology. Am J Pathol 172:555–565PubMed
116.
Kriegstein A, Alvarez-Buylla A (2009) The glial nature of embryonic and adult neural stem cells. Annu Rev Neurosci 32:149–184PubMed
117.
Kuhlmann T, Lassmann H, Bruck W (2008) Diagnosis of inflammatory demyelination in biopsy specimens: a practical approach. Acta Neuropathol 115:275–287PubMed
118.
Laks DR, Masterman-Smith M, Visnyei K, Angenieux B, Orozco NM, Foran I, Yong WH, Vinters HV, Liau LM, Lazareff JA, Mischel PS, Cloughesy TF, Horvath S, Kornblum HI (2009) Neurosphere formation is an independent predictor of clinical outcome in malignant glioma. Stem Cells 27:980–987PubMed
119.
Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR (2005) IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 202:473–477PubMed
120.
Lepore AC, Rauck B, Dejea C, Pardo AC, Rao MS, Rothstein JD, Maragakis NJ (2008) Focal transplantation-based astrocyte replacement is neuroprotective in a model of motor neuron disease. Nat Neurosci 11:1294–1301PubMed
121.
Levison SW, Jiang FJ, Stoltzfus OK, Ducceschi MH (2000) IL-6-type cytokines enhance epidermal growth factor-stimulated astrocyte proliferation. Glia 32:328–337PubMed
122.
Levitt P, Rakic P (1980) Immunoperoxidase localization of glial fibrillary acidic protein in radial glial cells and astrocytes of the developing rhesus monkey brain. J Comp Neurol 193:815–840PubMed
123.
Li L, Lundkvist A, Andersson D, Wilhelmsson U, Nagai N, Pardo AC, Nodin C, Stahlberg A, Aprico K, Larsson K, Yabe T, Moons L, Fotheringham A, Davies I, Carmeliet P, Schwartz JP, Pekna M, Kubista M, Blomstrand F, Maragakis N, Nilsson M, Pekny M (2008) Protective role of reactive astrocytes in brain ischemia. J Cereb Blood Flow Metab 28:468–481PubMed
124.
Lim MC, Maubach G, Zhuo L (2008) Glial fibrillary acidic protein splice variants in hepatic stellate cells–expression and regulation. Mol Cells 25:376–384PubMed
125.
Lin JH, Lou N, Kang N, Takano T, Hu F, Han X, Xu Q, Lovatt D, Torres A, Willecke K, Yang J, Kang J, Nedergaard M (2008) A central role of connexin 43 in hypoxic preconditioning. J Neurosci 28:681–695PubMed
126.
Liu X, Bolteus AJ, Balkin DM, Henschel O, Bordey A (2006) GFAP-expressing cells in the postnatal subventricular zone display a unique glial phenotype intermediate between radial glia and astrocytes. Glia 54:394–410PubMed
127.
Lobsiger CS, Cleveland DW (2007) Glial cells as intrinsic components of non-cell-autonomous neurodegenerative disease. Nat Neurosci 10:1355–1360PubMed
128.
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109PubMed
129.
Lovatt D, Sonnewald U, Waagepetersen HS, Schousboe A, He W, Lin JH, Han X, Takano T, Wang S, Sim FJ, Goldman SA, Nedergaard M (2007) The transcriptome and metabolic gene signature of protoplasmic astrocytes in the adult murine cortex. J Neurosci 27:12255–12266PubMed
130.
131.
Lutz SE, Zhao Y, Gulinello M, Lee SC, Raine CS, Brosnan CF (2009) Deletion of astrocyte connexins 43 and 30 leads to a dysmyelinating phenotype and hippocampal CA1 vacuolation. J Neurosci 29:7743–7752PubMed
132.
Maginnis MS, Atwood WJ (2009) JC virus: an oncogenic virus in animals and humans? Semin Cancer Biol 19:261–269PubMed
133.
Magnus T, Carmen J, Deleon J, Xue H, Pardo AC, Lepore AC, Mattson MP, Rao MS, Maragakis NJ (2008) Adult glial precursor proliferation in mutant SOD1G93A mice. Glia 56:200–208PubMed
134.
Malatesta P, Hack MA, Hartfuss E, Kettenmann H, Klinkert W, Kirchhoff F, Götz M (2003) Neuronal or glial progeny: Regional differences in radial glia fate. Neuron 37:751–764PubMed
135.
Manley GT, Fujimura M, Ma T, Noshita N, Filiz F, Bollen AW, Chan P, Verkman AS (2000) Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke. Nat Med 6:159–163PubMed
136.
Maragakis NJ, Rothstein JD (2006) Mechanisms of Disease: astrocytes in neurodegenerative disease. Nat Clin Pract Neurol 2:679–689PubMed
137.
Matute C, Melone M, Vallejo-Illarramendi A, Conti F (2005) Increased expression of the astrocytic glutamate transporter GLT-1 in the prefrontal cortex of schizophrenics. Glia 49:451–455PubMed
138.
McArthur DL, Chute DJ, Villablanca JP (2004) Moderate and severe traumatic brain injury: epidemiologic, imaging and neuropathologic perspectives. Brain Pathol 14:185–194PubMed
139.
McCarty JH (2009) Cell adhesion and signaling networks in brain neurovascular units. Curr Opin Hematol 16:209–214PubMed
140.
McGeer PL, McGeer EG (2008) Glial reactions in Parkinson’s disease. Mov Disord 23:474–483PubMed
141.
Meletis K, Barnabe-Heider F, Carlen M, Evergren E, Tomilin N, Shupliakov O, Frisen J (2008) Spinal cord injury reveals multilineage differentiation of ependymal cells. PLoS Biol 6:e182PubMed
142.
Merkle FT, Tramontin AD, Garcia-Verdugo JM, Alvarez-Buylla A (2004) Radial glia give rise to adult neural stem cells in the subventricular zone. Proc Natl Acad Sci USA 101:17528–17532PubMed
143.
Messing A, Head MW, Galles K, Galbreath EJ, Goldman JE, Brenner M (1998) Fatal encephalopathy with astrocyte inclusions in GFAP transgenic mice. Am J Pathol 152:391–398PubMed
144.
Meyer EM, St.Onge E, Crews FT (1984) Effects of aging on rat cortical presynaptic cholinergic processes. Neurobiol Aging 5:315–317PubMed
145.
Miguel-Hidalgo JJ (2009) The role of glial cells in drug abuse. Curr Drug Abuse Rev 2:72–82PubMed
146.
Miguel-Hidalgo JJ, Baucom C, Dilley G, Overholser JC, Meltzer HY, Stockmeier CA, Rajkowska G (2000) Glial fibrillary acidic protein immunoreactivity in the prefrontal cortex distinguishes younger from older adults in major depressive disorder. Biol Psychiatry 48:861–873PubMed
147.
Milligan ED, Watkins LR (2009) Pathological and protective roles of glia in chronic pain. Nat Rev Neurosci 10:23–36PubMed
148.
Min KJ, Yang MS, Kim SU, Jou I, Joe EH (2006) Astrocytes induce hemeoxygenase-1 expression in microglia: a feasible mechanism for preventing excessive brain inflammation. J Neurosci 26:1880–1887PubMed
149.
Mirza B, Hadberg H, Thomsen P, Moos T (2000) The absence of reactive astrocytosis is indicative of a unique inflammatory process in Parkinson’s disease. Neuroscience 95:425–432PubMed
150.
Mischel PS, Nguyen LP, Vinters HV (1995) Cerebral cortical dysplasia associated with pediatric epilepsy Review of neuropathologic features and proposal for a grading system. J Neuropathol Exp Neurol 54:137–153PubMed
151.
Mitterauer B (2005) Nonfunctional glial proteins in tripartite synapses: a pathophysiological model of schizophrenia. Neuroscientist 11:192–198PubMed
152.
Miyata H, Chiang AC, Vinters HV (2004) Insulin signaling pathways in cortical dysplasia and TSC-tubers: tissue microarray analysis. Ann Neurol 56:510–519PubMed
153.
Morest DK, Silver J (2003) Precursors of neurons, neuroglia, and ependymal cells in the CNS: what are they? Where are they from? How do they get where they are going? Glia 43:6–18PubMed
154.
Moseley AE, Williams MT, Schaefer TL, Bohanan CS, Neumann JC, Behbehani MM, Vorhees CV, Lingrel JB (2007) Deficiency in Na, K-ATPase alpha isoform genes alters spatial learning, motor activity, and anxiety in mice. J Neurosci 27:616–626PubMed
155.
Muller W, Dahmen HG (1978) Lymphocytes within glial cells (“emperipolesis”) in a case of a granular cell tumor. Acta Neuropathol 44:163–165PubMed
156.
Myer DJ, Gurkoff GG, Lee SM, Hovda DA, Sofroniew MV (2006) Essential protective roles of reactive astrocytes in traumatic brain injury. Brain 129:2761–2772PubMed
157.
Nag S, Manias JL, Stewart DJ (2009) Pathology and new players in the pathogenesis of brain edema. Acta Neuropathol 118:197–217PubMed
158.
Nagai M, Re DB, Nagata T, Chalazonitis A, Jessell TM, Wichterle H, Przedborski S (2007) Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons. Nat Neurosci 10:615–622PubMed
159.
Nagele RG, Wegiel J, Venkataraman V, Imaki H, Wang KC (2004) Contribution of glial cells to the development of amyloid plaques in Alzheimer’s disease. Neurobiol Aging 25:663–674PubMed
160.
Nakano I, Kornblum HI (2009) Methods for analysis of brain tumor stem cell and neural stem cell self-renewal. Methods Mol Biol 568:37–56PubMed
161.
Neary JT, Zimmermann H (2009) Trophic functions of nucleotides in the central nervous system. Trends Neurosci 32:189–198PubMed
162.
Nedergaard M, Ransom B, Goldman SA (2003) New roles for astrocytes: redefining the functional architecture of the brain. Trends Neurosci 26:523–530PubMed
163.
Nishie M, Mori F, Ogawa M, Sannohe S, Tanno K, Kurahashi K, Kuroda N, Wakabayashi K (2004) Multinucleated astrocytes in old demyelinated plaques in a patient with multiple sclerosis. Neuropathology 24:248–253PubMed
164.
Noctor SC, Flint AC, Weissman TA, Dammerman RS, Kriegstein AR (2001) Neurons derived from radial glial cells establish radial units in neocortex. Nature 409:714–720PubMed
165.
Norenberg MD (1979) Distribution of glutamine synthetase in the rat central nervous system. J Histochem Cytochem 27:756–762PubMed
166.
Norenberg MD, Rao KV, Jayakumar AR (2005) Mechanisms of ammonia-induced astrocyte swelling. Metab Brain Dis 20:303–318PubMed
167.
Norton WT, Aquino DA, Hozumi I, Chiu FC, Brosnan CF (1992) Quantitative aspects of reactive gliosis: a review. Neurochem Res 17:877–885PubMed
168.
Obara M, Szeliga M, Albrecht J (2008) Regulation of pH in the mammalian central nervous system under normal and pathological conditions: facts and hypotheses. Neurochem Int 52:905–919PubMed
169.
Oberheim NA, Tian GF, Han X, Peng W, Takano T, Ransom B, Nedergaard M (2008) Loss of astrocytic domain organization in the epileptic brain. J Neurosci 28:3264–3276PubMed
170.
Oberheim NA, Takano T, Han X, He W, Lin JH, Wang F, Xu Q, Wyatt JD, Pilcher W, Ojemann JG, Ransom BR, Goldman SA, Nedergaard M (2009) Uniquely hominid features of adult human astrocytes. J Neurosci 29:3276–3287PubMed
171.
Occhipinti R, Somersalo E, Calvetti D (2009) Astrocytes as the glucose shunt for glutamatergic neurons at high activity: an in silico study. J Neurophysiol 101:2528–2538PubMed
172.
Ogata K, Kosaka T (2002) Structural and quantitative analysis of astrocytes in the mouse hippocampus. Neuroscience 113:221–233PubMed
173.
Ohab JJ, Fleming S, Blesch A, Carmichael ST (2006) A neurovascular niche for neurogenesis after stroke. J Neurosci 26:13007–13016PubMed
174.
Oide T, Yoshida K, Kaneko K, Ohta M, Arima K (2006) Iron overload and antioxidative role of perivascular astrocytes in aceruloplasminemia. Neuropathol Appl Neurobiol 32:170–176PubMed
175.
Okada S, Nakamura M, Katoh H, Miyao T, Shimazaki T, Ishii K, Yamane J, Yoshimura A, Iwamoto Y, Toyama Y, Okano H (2006) Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury. Nature Med 12:829–834PubMed
176.
Omary MB, Lugea A, Lowe AW, Pandol SJ (2007) The pancreatic stellate cell: a star on the rise in pancreatic diseases. J Clin Invest 117:50–59PubMed
177.
Papadopoulos MC, Manley GT, Krishna S, Verkman AS (2004) Aquaporin-4 facilitates reabsorption of excess fluid in vasogenic brain edema. FASEB J 18:1291–1293PubMed
178.
Patel SC, Suresh S, Kumar U, Hu CY, Cooney A, Blanchette-Mackie EJ, Neufeld EB, Patel RC, Brady RO, Patel YC, Pentchev PG, Ong WY (1999) Localization of Niemann-Pick C1 protein in astrocytes: implications for neuronal degeneration in Niemann- Pick type C disease. Proc Natl Acad Sci USA 96:1657–1662PubMed
179.
Pekny M, Pekna M (2004) Astrocyte intermediate filaments in CNS pathologies and regeneration. J Pathol 204:428–437PubMed
180.
Pekny M, Leveen P, Pekna M, Eliasson C, Berthold CH, Westermark B, Betsholtz C (1995) Mice lacking glial fibrillary acidic protein display astrocytes devoid of intermediate filaments but develop and reproduce normally. EMBO J 14:1590–1598PubMed
181.
Pellerin L, Bouzier-Sore AK, Aubert A, Serres S, Merle M, Costalat R, Magistretti PJ (2007) Activity-dependent regulation of energy metabolism by astrocytes: an update. Glia 55:1251–1262PubMed
182.
Perea G, Navarrete M, Araque A (2009) Tripartite synapses: astrocytes process and control synaptic information. Trends Neurosci 32:t421–t431
183.
Peters A, Palay SL, Webster HD (1991) The fine structure of the nervous system, Third edn. Oxford University Press, New York
184.
Phelps CH (1972) Barbiturate-induced glycogen accumulation in brain. An electron microscopic study. Brain Res 39:225–234PubMed
185.
Pittock SJ, Lucchinetti CF (2007) The pathology of MS: new insights and potential clinical applications. Neurologist 13:45–56PubMed
186.
Powell EM, Geller HM (1999) Dissection of astrocyte-mediated cues in neuronal guidance and process extension. Glia 26:73–83PubMed
187.
Przedborski S, Jackson-Lewis V, Djaldetti R, Liberatore G, Vila M, Vukosavic S, Almer G (2000) The parkinsonian toxin MPTP: action and mechanism. Restor Neurol Neurosci 16:135–142PubMed
188.
Pun PB, Lu J, Moochhala S (2009) Involvement of ROS in BBB dysfunction. Free Radic Res 43:348–364PubMed
189.
Rajkowska G, Miguel-Hidalgo JJ (2007) Gliogenesis and glial pathology in depression. CNS Neurol Disord Drug Targets 6:219–233PubMed
190.
Rajkowska G, Miguel-Hidalgo JJ, Makkos Z, Meltzer H, Overholser J, Stockmeier C (2002) Layer-specific reductions in GFAP-reactive astroglia in the dorsolateral prefrontal cortex in schizophrenia. Schizophr Res 57:127–138PubMed
191.
Ramon Y, Cajal S (1909) Histologie du systeme nerveux de l’homme et des vertebres. Maloine, Paris
192.
Ramon y Cajal S (1928) Degeneration and regeneration of the nervous system. Oxford University Press, London
193.
Rao KV, Panickar KS, Jayakumar AR, Norenberg MD (2005) Astrocytes protect neurons from ammonia toxicity. Neurochem Res 30:1311–1318PubMed
194.
Rattray M, Bendotti C (2006) Does excitotoxic cell death of motor neurons in ALS arise from glutamate transporter and glutamate receptor abnormalities? Exp Neurol 201:15–23PubMed
195.
Roelofs RF, Fischer DF, Houtman SH, Sluijs JA, Van Haren W, Van Leeuwen FW, Hol EM (2005) Adult human subventricular, subgranular, and subpial zones contain astrocytes with a specialized intermediate filament cytoskeleton. Glia 52:289–300PubMed
196.
Rossi DJ, Brady JD, Mohr C (2007) Astrocyte metabolism and signaling during brain ischemia. Nat Neurosci 10:1377–1386PubMed
197.
Rothstein JD, Martin LJ, Kuncl RW (1992) Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis. N Engl J Med 326:1464–1468PubMedCrossRef
198.
Rothstein JD, Dykes-Hoberg M, Pardo CA, Bristol LA, Jin L, Kunci RW, Kanai Y, Hediger MA, Wang Y, Schielke JP, Welty DF (1996) Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 16:675–686PubMed
199.
Rothstein JD, Patel S, Regan MR, Haenggeli C, Huang YH, Bergles DE, Jin L, Dykes Hoberg M, Vidensky S, Chung DS, Toan SV, Bruijn LI, Su ZZ, Gupta P, Fisher PB (2005) Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Nature 433:73–77PubMed
200.
Rouach N, Koulakoff A, Abudara V, Willecke K, Giaume C (2008) Astroglial metabolic networks sustain hippocampal synaptic transmission. Science 322:1551–1555PubMed
201.
Rowland LP, Shneider NA (2001) Amyotrophic lateral sclerosis. N Engl J Med 344:1688–1700PubMed
202.
Ruhl A (2005) Glial cells in the gut. Neurogastroenterol Motil 17:777–790PubMed
203.
Saijo K, Winner B, Carson CT, Collier JG, Boyer L, Rosenfeld MG, Gage FH, Glass CK (2009) A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. Cell 137:47–59PubMed
204.
Sanchez-Del-Rio M, Reuter U, Moskowitz MA (2006) New insights into migraine pathophysiology. Curr Opin Neurol 19:294–298PubMed
205.
Sattler R, Rothstein JD (2006) Regulation and dysregulation of glutamate transporters. Handb Exp Pharmacol 175:277–303
206.
Saunders NR, Ek CJ, Habgood MD, Dziegielewska KM (2008) Barriers in the brain: a renaissance? Trends Neurosci 31:279–286PubMed
207.
Savidge TC, Sofroniew MV, Neunlist M (2007) Starring roles for astroglia in barrier pathologies of gut and brain. Lab Invest 87:731–736PubMed
208.
Savidge TC, Newman P, Pothoulakis C, Ruhl A, Neunlist M, Bourreille A, Hurst R, Sofroniew MV (2007) Enteric glia regulate intestinal barrier function and inflammation via release of S-nitrosoglutathione. Gastroenterology 132:1344–1358PubMed
209.
Schlondorff D, Banas B (2009) The mesangial cell revisited: no cell is an island. J Am Soc Nephrol 20:1179–1187PubMed
210.
Schmitt A, Gofferje V, Weber M, Meyer J, Mossner R, Lesch KP (2003) The brain-specific protein MLC1 implicated in megalencephalic leukoencephalopathy with subcortical cysts is expressed in glial cells in the murine brain. Glia 44:283–295PubMed
211.
Schummers J, Yu H, Sur M (2008) Tuned responses of astrocytes and their influence on hemodynamic signals in the visual cortex. Science 320:1638–1643PubMed
212.
Seifert G, Schilling K, Steinhauser C (2006) Astrocyte dysfunction in neurological disorders: a molecular perspective. Nat Rev Neurosci 7:194–206PubMed
213.
Semmler A, Okulla T, Sastre M, Dumitrescu-Ozimek L, Heneka MT (2005) Systemic inflammation induces apoptosis with variable vulnerability of different brain regions. J Chem Neuroanat 30:144–157PubMed
214.
Seri B, Garcia-Verdugo JM, McEwen BS, Alvarez-Buylla A (2001) Astrocytes give rise to new neurons in the adult mammalian hippocampus. J Neurosci 21:7153–7160PubMed
215.
Shigetomi E, Bowser DN, Sofroniew MV, Khakh BS (2008) Two forms of astrocyte calcium excitability have distinct effects on NMDA receptor-mediated slow inward currents in pyramidal neurons. J Neurosci 28:6659–6663PubMed
216.
Shih AY, Johnson DA, Wong G, Kraft AD, Jiang L, Erb H, Johnson JA, Murphy TH (2003) Coordinate regulation of glutathione biosynthesis and release by Nrf2-expressing glia potently protects neurons from oxidative stress. J Neurosci 23:3394–3406PubMed
217.
Shintaku M, Yutani C (2004) Oligodendrocytes within astrocytes (“emperipolesis”) in the white matter in Creutzfeldt-Jakob disease. Acta Neuropathol 108:201–206PubMed
218.
Si X, Miguel-Hidalgo JJ, O’Dwyer G, Stockmeier CA, Rajkowska G (2004) Age-dependent reductions in the level of glial fibrillary acidic protein in the prefrontal cortex in major depression. Neuropsychopharmacology 29:2088–2096PubMed
219.
Silver J, Miller JH (2004) Regeneration beyond the glial scar. Nature Rev Neurosci 5:146–156
220.
Simard M, Nedergaard M (2004) The neurobiology of glia in the context of water and ion homeostasis. Neuroscience 129:877–896PubMed
221.
Simpson JE, Ince PG, Lace G, Forster G, Shaw PJ, Matthews F, Savva G, Brayne C, Wharton SB (2008) Astrocyte phenotype in relation to Alzheimer-type pathology in the ageing brain. Neurobiol Aging (Epub 1 July 2008)
222.
Singh N, Paterson DL (2000) Encephalitis caused by human herpesvirus-6 in transplant recipients: relevance of a novel neurotropic virus. Transplantation 69:2474–2479PubMed
223.
Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432:396–401PubMed
224.
Sofroniew MV (2000) Astrocyte failure as a cause of CNS dysfunction. Mol Psychiatry 5:230–232PubMed
225.
Sofroniew MV (2005) Reactive astrocytes in neural repair and protection. Neuroscientist 5:400–407
226.
Sofroniew MV (2009) Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci 32:638–647PubMed
227.
Song YJC, Halliday GM, Holton JL, Lashley T, O’Sullivan SS, McCann H, Lees AJ, Ozawa T, Williams DR, Lockhart PJ, Revesz TR (2009) Degeneration in different parkinsonian syndromes relates to astrocyte type and astrocyte protein expression. J Neuropathol Exp Neurol 68:1073–1083PubMed
228.
Sontheimer H (2008) A role for glutamate in growth and invasion of primary brain tumors. J Neurochem 105:287–295PubMed
229.
Stellwagen D, Malenka RC (2006) Synaptic scaling mediated by glial TNF-alpha. Nature 440:1054–1059PubMed
230.
Stevens B, Allen NJ, Vazquez LE, Howell GR, Christopherson KS, Nouri N, Micheva KD, Mehalow AK, Huberman AD, Stafford B, Sher A, Litke AM, Lambris JD, Smith SJ, John SW, Barres BA (2007) The classical complement cascade mediates CNS synapse elimination. Cell 131:1164–1178PubMed
231.
Suh SW, Bergher JP, Anderson CM, Treadway JL, Fosgerau K, Swanson RA (2007) Astrocyte glycogen sustains neuronal activity during hypoglycemia: studies with the glycogen phosphorylase inhibitor CP-316, 819 ([R-R*, S*]-5-chloro-N-[2-hydroxy-3-(methoxymethylamino)-3-oxo-1-(phenylmet hyl)propyl]-1H-indole-2-carboxamide). J Pharmacol Exp Ther 321:45–50PubMed
232.
Sun D, Lye-Barthel M, Masland RH, Jakobs TC (2009) The morphology and spatial arrangement of astrocytes in the optic nerve head of the mouse. J Comp Neurol 516:1–19PubMed
233.
Suzuki M, McHugh J, Tork C, Shelley B, Klein SM, Aebischer P, Svendsen CN (2007) GDNF secreting human neural progenitor cells protect dying motor neurons, but not their projection to muscle, in a rat model of familial ALS. PLoS One 2:e689PubMed
234.
Swanson RA, Ying W, Kauppinen TM (2004) Astrocyte influences on ischemic neuronal death. Curr Mol Med 4:193–205PubMed
235.
Szymocha R, Akaoka H, Dutuit M, Malcus C, Didier-Bazes M, Belin MF, Giraudon P (2000) Human T-cell lymphotropic virus type 1-infected T lymphocytes impair catabolism and uptake of glutamate by astrocytes via Tax-1 and tumor necrosis factor alpha. J Virol 74:6433–6441PubMed
236.
Takahashi T, Fujihara K, Nakashima I, Misu T, Miyazawa I, Nakamura M, Watanabe S, Shiga Y, Kanaoka C, Fujimori J, Sato S, Itoyama Y (2007) Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre. Brain 130:1235–1243PubMed
237.
Takano T, Oberheim N, Cotrina ML, Nedergaard M (2009) Astrocytes and ischemic injury. Stroke 40:S8–12PubMed
238.
Takano T, Kang J, Jaiswal JK, Simon SM, Lin JH, Yu Y, Li Y, Yang J, Dienel G, Zielke HR, Nedergaard M (2005) Receptor-mediated glutamate release from volume sensitive channels in astrocytes. Proc Natl Acad Sci USA 102:16466–16471PubMed
239.
Thal DR, Schultz C, Dehghani F, Yamaguchi H, Braak H, Braak E (2000) Amyloid beta-protein (Abeta)-containing astrocytes are located preferentially near N-terminal-truncated Abeta deposits in the human entorhinal cortex. Acta Neuropathol 100:608–617PubMed
240.
Tian GF, Azmi H, Takano T, Xu Q, Peng W, Lin J, Oberheim N, Lou N, Wang X, Zielke HR, Kang J, Nedergaard M (2005) An astrocytic basis of epilepsy. Nat Med 11:973–981PubMed
241.
Tiegs G, Lohse AW (2009) Immune tolerance: what is unique about the liver. J Autoimmun (Epub 1 September 2009)
242.
Tomita M, Khan RL, Blehm BH, Santoro TJ (2004) The potential pathogenetic link between peripheral immune activation and the central innate immune response in neuropsychiatric systemic lupus erythematosus. Med Hypotheses 62:325–335PubMed
243.
Ullian EK, Sapperstein SK, Christopherson KS, Barres BA (2001) Control of synapse number by glia. Science 291:657–661PubMed
244.
van Kollenburg B, van Dijk J, Garbern J, Thomas AA, Scheper GC, Powers JM, van der Knaap MS (2006) Glia-specific activation of all pathways of the unfolded protein response in vanishing white matter disease. J Neuropathol Exp Neurol 65:707–715PubMed
245.
Vargas MR, Johnson DA, Sirkis DW, Messing A, Johnson JA (2008) Nrf2 activation in astrocytes protects against neurodegeneration in mouse models of familial amyotrophic lateral sclerosis. J Neurosci 28:13574–13581PubMed
246.
Vinters HV, Miyata H (2006) Neuropathologic features of tuberous sclerosis. In: McLendon RE, Rosenblum MK, Bigner DD (eds) Russel and Rubenstein’s Pathology of Tumors of the Nervous System, 7th edn. Hodder Arnold, Oxford, pp 955–969
247.
Vinters HV, Farrell MA, Mischel PS, Anders K (1998) Diagnostic Neuropathology. Marcel Dekker, Inc., New York
248.
Vinters HV, Kwok MK, Ho HW, Anders KH, Tomiyasu U, Wolfson WL, Robert F (1989) Cytomegalovirus in the nervous system of patients with the acquired immune deficiency syndrome. Brain 112(Pt 1):245–268PubMed
249.
Volterra A, Meldolesi J (2005) Astrocytes, from brain glue to communication elements: the revolution continues. Nat Rev Neurosci 6:626–640PubMed
250.
von Einsiedel RW, Samorei IW, Pawlita M, Zwissler B, Deubel M, Vinters HV (2004) New JC virus infection patterns by in situ polymerase chain reaction in brains of acquired immunodeficiency syndrome patients with progressive multifocal leukoencephalopathy. J Neurovirol 10:1–11
251.
Voskuhl RR, Peterson RS, Song B, Ao Y, Morales LB, Tiwari-Woodruff S, Sofroniew MV (2009) Reactive astrocytes form scar-like perivascular barriers to leukocytes during adaptive immune inflammation of the CNS. J Neurosci 29:11511–11522PubMed
252.
Voutsinos-Porche B, Bonvento G, Tanaka K, Steiner P, Welker E, Chatton JY, Magistretti PJ, Pellerin L (2003) Glial glutamate transporters mediate a functional metabolic crosstalk between neurons and astrocytes in the mouse developing cortex. Neuron 37:275–286PubMed
253.
Wang Z, Trillo-Pazos G, Kim SY, Canki M, Morgello S, Sharer LR, Gelbard HA, Su ZZ, Kang DC, Brooks AI, Fisher PB, Volsky DJ (2004) Effects of human immunodeficiency virus type 1 on astrocyte gene expression and function: potential role in neuropathogenesis. J Neurovirol 10(Suppl 1):25–32
254.
Weggen S, Diehlmann A, Buslei R, Beyreuther K, Bayer TA (1998) Prominent expression of presenilin-1 in senile plaques and reactive astrocytes in Alzheimer’s disease brain. Neuroreport 9:3279–3283PubMed
255.
Weidenfeller C, Svendsen CN, Shusta EV (2007) Differentiating embryonic neural progenitor cells induce blood-brain barrier properties. J Neurochem 101:555–565PubMed
256.
Whitney KD, McNamara JO (2000) GluR3 autoantibodies destroy neural cells in a complement-dependent manner modulated by complement regulatory proteins. J Neurosci 20:7307–7316PubMed
257.
Wilhelmsson U, Bushong EA, Price DL, Smarr BL, Phung V, Terada M, Ellisman MH, Pekny M (2006) Redefining the concept of reactive astrocytes as cells that remain within their unique domains upon reaction to injury. Proc Natl Acad Sci USA 103:17513–17518PubMed
258.
Winau F, Quack C, Darmoise A, Kaufmann SH (2008) Starring stellate cells in liver immunology. Curr Opin Immunol 20:68–74PubMed
259.
Winau F, Hegasy G, Weiskirchen R, Weber S, Cassan C, Sieling PA, Modlin RL, Liblau RS, Gressner AM, Kaufmann SH (2007) Ito cells are liver-resident antigen-presenting cells for activating T cell responses. Immunity 26:117–129PubMed
260.
Wolf F, Kirchhoff F (2008) Neuroscience. Imaging astrocyte activity. Science 320:1597–1599PubMed
261.
Wyss-Coray T, Loike JD, Brionne TC, Lu E, Anankov R, Yan F, Silverstein SC, Husemann J (2003) Adult mouse astrocytes degrade amyloid-beta in vitro and in situ. Nat Med 9:453–457PubMed
262.
Yang H, Downs JC, Sigal IA, Roberts MD, Thompson H, Burgoyne CF (2009) Deformation of the normal monkey optic nerve head connective tissue following acute iop elevation within 3-D histomorphometric reconstructions. Invest Ophthalmol Vis Sci (Epub 2009/2007/2025)
263.
Yeh TH, Lee da Y, Gianino SM, Gutmann DH (2009) Microarray analyses reveal regional astrocyte heterogeneity with implications for neurofibromatosis type 1 (NF1)-regulated glial proliferation. Glia 57:1239–1249PubMed
264.
Zador Z, Stiver S, Wang V, Manley GT (2009) Role of aquaporin-4 in cerebral edema and stroke. Handb Exp Pharmacol 190:159–170PubMed
265.
Zhang M, Strnatka D, Donohue C, Hallows JL, Vincent I, Erickson RP (2008) Astrocyte-only Npc1 reduces neuronal cholesterol and triples life span of Npc1-/- mice. J Neurosci Res 86:2848–2856PubMed
266.
Zhao L, Burt AD (2007) The diffuse stellate cell system. J Mol Histol 38:53–64PubMed
Metadata
Title
Astrocytes: biology and pathology
Authors
Michael V. Sofroniew
Harry V. Vinters
Publication date
01-01-2010
Publisher
Springer-Verlag
Published in
Acta Neuropathologica / Issue 1/2010
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-009-0619-8

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