Neurological diseases as primary gliopathies: A reassessment of neurocentrism

ASN Neuro

Volumn 4, Issue 3, 2012, Pages 131-149

  Verkhratsky, Alexei ^a,b,c   Sofroniew, Michael V ^d   Messing, Albee ^e   deLanerollei, Nihal C ^f   Rempe, David ^g   Rodríguez, José Julio ^a,b,h   Nedergaard, Maiken ^a,g  

^a UNIVERSITY OF MANCHESTER   (United Kingdom)

^b BASQUE FOUNDATION FOR SCIENCE   (Spain)

^c UNIVERSITY OF THE BASQUE COUNTRY UPV EHU   (Spain)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e UNIVERSITY OF WISCONSIN MADISON   (United States)

^f YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^g UNIVERSITY OF ROCHESTER SCHOOL OF MEDICINE AND DENTISTRY   (United States)

^h INSTITUTE OF EXPERIMENTAL MEDICINE   (Czech Republic)

Author keywords

Aging; Astrocyte; Brain; Calcium; Disease; Supportive cell; Transmitter

Indexed keywords

ARUNDIC ACID; ERYTHROPOIETIN; GELATINASE B; GLIAL FIBRILLARY ACIDIC PROTEIN; GLUTAMATE AMMONIA LIGASE; NEUROPROTECTIVE AGENT; PROTEIN S100B; THROMBOSPONDIN 1; THROMBOSPONDIN 2; VASCULOTROPIN; VIMENTIN;

ALEXANDER DISEASE; ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; ASTROCYTE; ASTROCYTOSIS; BRAIN ISCHEMIA; CELL DEATH; DEMENTIA; DRUG EFFICACY; DRUG SAFETY; EPILEPSY; GAIN OF FUNCTION MUTATION; GENE; GFAP GENE; HIPPOCAMPAL SCLEROSIS; HOMEOSTASIS; HUMAN; LOSS OF FUNCTION MUTATION; MACROGLIA; NERVE DEGENERATION; NEUROLOGIC DISEASE; NEUROPATHOLOGY; NEUROPROTECTION; NONHUMAN; PARKINSON DISEASE; REACTIVE ASTROGLIOSIS; REVIEW; STROKE; TSC1 GENE; WERNICKE ENCEPHALOPATHY;

EID: 84860555370     PISSN: None     EISSN: 17590914     Source Type: Journal    
DOI: 10.1042/AN20120010     Document Type: Review

References (150)

1. Abbott NJ (2005) Dynamics of CNS barriers: evolution, differentiation, and modulation. Cell Mol Neurobiol 25:5-23.
2. Alexander WS (1949) Progressive fibrinoid degeneration of fibrillary astrocytes associated with mental retardation in a hydrocephalic infant. Brain 72:373-381.
3. Allaman I, Gavillet M, Belanger M, Laroche T, Viertl D, Lashuel HA, Magistretti PJ (2010) Amyloid-b aggregates cause alterations of astrocytic metabolic phenotype: impact on neuronal viability. J Neurosci 30:3326-3338.
4. Alvarez-Buylla A, Garcia-Verdugo JM, Tramontin AD (2001) A unified hypothesis on the lineage of neural stem cells. Nat Rev Neurosci 2:287-293.
5. Alzheimer A (1910) Beiträge zur Kenntnis der pathologischen Neuroglia und ihrer Beziehungen zu den Abbauvorgängen im Nervengewebe. In: Nissl FAlzheimer A (eds) Histologische und Histopathologische Arbeiten über die Grosshirnrinde mit besonderer Berücksichtigung der pathologischen Anatomie der Geisteskrankheiten. Verlag von Gustav Fischer Jena, pp 401-562.
6. Apelt J, Ach K, Schliebs R (2003) Aging-related down-regulation of neprilysin, a putative b-amyloid-degrading enzyme, in transgenic Tg2576 Alzheimer-like mouse brain is accompanied by an astroglial upregulation in the vicinity of beta-amyloid plaques. Neurosci Lett 339:183-186.
7. Aronica E, Boer K, van Vliet EA, Redeker S, Baayen JC, Spliet WG, van Rijen PC, Troost D, da Silva FH, Wadman WJ, Gorter JA (2007) Complement activation in experimental and human temporal lobe epilepsy. Neurobiol Dis 26:497-511.
8. Barres BA (2008) The mystery and magic of glia: a perspective on their roles in health and disease. Neuron 60:430-440.
9. Barrett KM, Ding YH, Wagner DP, Kallmes DF, Johnston KC (2009) Change in diffusion-weighted imaging infarct volume predicts neurologic outcome at 90 days: results of the acute stroke accurate prediction (ASAP) trial serial imaging substudy. Stroke 40:2422-2427.
10. Beach TG, McGeer EG (1988) Lamina-specific arrangement of astrocytic gliosis and senile plaques in Alzheimer's disease visual cortex. Brain Res 463:357-361.
11. Beaulieu C, de Crespigny A, Tong DC, Moseley ME, Albers GW, Marks MP (1999) Longitudinal magnetic resonance imaging study of perfusion and diffusion in stroke: evolution of lesion volume and correlation with clinical outcome. Ann Neurol 46:568-578.
12. Bernaudin M, Marti HH, Roussel S, Divoux D, Nouvelot A, MacKenzie ET, Petit E (1999) A potential role for erythropoietin in focal permanent cerebral ischemia in mice. J Cereb Blood Flow Metab 19:643-651.
13. Bordey A, Sontheimer H (1998) Properties of human glial cells associated with epileptic seizure foci. Epilepsy Res 32:286-303.
14. Bourne JN, Harris KM (2008) Balancing structure and function at hippocampal dendritic spines. Annu Rev Neurosci 31:47-67.
15. Brady JP, Garland DL, Green DE, Tamm ER, Giblin FJ, Wawrousek EF (2001) AB-crystallin in lens development and muscle integrity: a gene knockout approach. Invest Ophthalmol Vis Sci 42:2924-2934.
16. Brambilla R, Bracchi-Ricard V, Hu WH, Frydel B, Bramwell A, Karmally S, Green EJ, Bethea JR (2005) Inhibition of astroglial nuclear factor kB reduces inflammation and improves functional recovery after spinal cord injury. J Exp Med 202:145-156.
17. 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-kB improves functional outcome in experimental autoimmune encephalomyelitis by suppressing chronic central nervous system inflammation. J Immunol 182:2628-2640.
18. 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 27:117-120.
19. Brenner M, Goldman JE, Quinlan RA, Messing A (2009) Alexander disease: a genetic disorder of astrocytes. In Astrocytes in (Patho)Physiology of the Nervous System (Parpura V, Haydon PG eds), pp 591-648, Springer, New York.
20. Broe M, Kril J, Halliday GM (2004) Astrocytic degeneration relates to the severity of disease in frontotemporal dementia. Brain 127:2214-2220.
21. Brown AM, Ransom BR (2007) Astrocyte glycogen and brain energy metabolism. Glia 55:1263-1271.
22. Brown CE, Li P, Boyd JD, Delaney KR, Murphy TH (2007) Extensive turnover of dendritic spines and vascular remodeling in cortical tissues recovering from stroke. J Neurosci 27:4101-4109.
23. 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.
24. 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 scarforming, reactive astrocytes in adult transgenic mice. Neuron 23: 297-308.
25. Bushong EA, Martone ME, Jones YZ, Ellisman MH (2002) Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomical domains. J Neurosci 22:183-192.
26. Byts N, Siren AL (2009) Erythropoietin: a multimodal neuroprotective agent. Exp Transl Stroke Med 1:4.
27. Carmichael ST (2003) Plasticity of cortical projections after stroke. Neuroscientist 9:64-75.
28. Chavez JC, Baranova O, Lin J, Pichiule P (2006) The transcriptional activator hypoxia inducible factor 2 (HIF-2/EPAS-1) regulates the oxygendependent expression of erythropoietin in cortical astrocytes. J Neurosci 26:9471-9481.
29. Chen Y, Swanson RA (2003) Astrocytes and brain injury. J Cereb Blood Flow Metab 23:137-149.
30. Chen Y, Vartiainen NE, Ying W, Chan PH, Koistinaho J, Swanson RA (2001) Astrocytes protect neurons from nitric oxide toxicity by a glutathionedependent mechanism. J Neurochem 77:1601-1610.
31. Chesler M (2005) Failure and function of intracellular pH regulation in acute hypoxic-ischemic injury of astrocytes. Glia 50:398-406.
32. Cho W, Messing A (2009) Properties of astrocytes cultured from GFAP overexpressing and GFAP mutant mice. Exp Cell Res 315:1260-1272.
33. Cho W, Brenner M, Peters N, Messing A (2010) Drug screening to identify suppressors of GFAP expression. Hum Mol Genet 19:3169-3178.
34. 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 120:421-433.
35. Coleman P, Federoff H, Kurlan R (2004) A focus on the synapse for neuroprotection in Alzheimer disease and other dementias. Neurology 63:1155-1162.
36. Cunningham LA, Wetzel M, Rosenberg GA (2005) Multiple roles for MMPs and TIMPs in cerebral ischemia. Glia 50:329-339.
37. Danbolt NC (2001) Glutamate uptake. Progr Neurobiol 65:1-105.
38. de Lanerolle NC, Lee TS, Spencer DD (2010) Astrocytes and epilepsy. Neurotherapeutics 7:424-438.
39. DeKosky ST, Scheff SW (1990) Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity. Ann Neurol 27:457-464.
40. Del Bigio MR, Chudley AE, Sarnat HB, Campbell C, Goobie S, Chodirker BN, Selcen D (2011) Infantile muscular dystrophy in Canadian aboriginals is an aB-crystallinopathy. Ann Neurol 69:866-871.
41. Der Perng M, Su M, Wen SF, Li R, Gibbon T, Prescott AR, Brenner M, Quinlan RA (2006) The Alexander disease-causing glial fibrillary acidic protein mutant, R416W, accumulates into Rosenthal fibers by a pathway that involves filament aggregation and the association of aB-crystallin and HSP27. Am J Hum Genet 79:197-213.
42. Drage MG, Holmes GL, Seyfried TN (2002) Hippocampal neurons and glia in epileptic EL mice. J Neurocytol 31:681-692.
43. 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: 2683-2693.
44. During MJ, Spencer DD (1993) Extracellular hippocampal glutamate and spontaneous seizure in the conscious human brain. Lancet 341: 1607-1610.
45. Ehrenreich H, Hasselblatt M, Dembowski C, Cepek L, Lewczuk P, Stiefel M, Rustenbeck HH, Breiter N, Jacob S, Knerlich F, Bohn M, Poser W, Ruther E, Kochen M, Gefeller O, Gleiter C, Wessel TC, De Ryck M, Itri L, Prange H, Cerami A, Brines M, Siren AL (2002) Erythropoietin therapy for acute stroke is both safe and beneficial. Mol Med 8:495-505.
46. Ehrenreich H, Weissenborn K, Prange H, Schneider D, Weimar C, Wartenberg K, Schellinger PD, Bohn M, Becker H, Wegrzyn M, Jahnig P, Herrmann M, Knauth M, Bahr M, Heide W, Wagner A, Schwab S, Reichmann H, Schwendemann G, Dengler R, Kastrup A, Bartels C (2009) Recombinant human erythropoietin in the treatment of acute ischemic stroke. Stroke 40:e647-e656.
47. Eid T, Thomas MJ, Spencer DD, Runden-Pran E, Lai JC, Malthankar GV, Kim JH, Danbolt NC, Ottersen OP, de Lanerolle NC (2004) Loss of glutamine synthetase in the human epileptogenic hippocampus: possible mechanism for raised extracellular glutamate in mesial temporal lobe epilepsy. Lancet 363:28-37.
48. 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.
49. Foerster O, Penfield W (1930) The structural basis of traumatic epilepsy and results of radical operations. Brain 53:99-119.
50. Garcia JH, Yoshida Y, Chen H, Li Y, Zhang ZG, Lian J, Chen S, Chopp M (1993) Progression from ischemic injury to infarct following middle cerebral artery occlusion in the rat. Am J Pathol 142:623-635.
51. Giaume C, Kirchhoff F, Matute C, Reichenbach A, Verkhratsky A (2007) Glia: the fulcrum of brain diseases. Cell Death Differ 14:1324-1335.
52. Giffard RG, Monyer H, Choi DW (1990) Selective vulnerability of cultured cortical glia to injury by extracellular acidosis. Brain Res 530:138-141.
53. Giffard RG, Papadopoulos MC, van Hooft JA, Xu L, Giuffrida R, Monyer H (2000) The electrogenic sodium bicarbonate cotransporter: developmental expression in rat brain and possible role in acid vulnerability. J Neurosci 20:1001-1008.
54. Gomi H, Yokoyama T, Fujimoto K, Ikeda T, Katoh A, Itoh T, Itohara S (1995) Mice devoid of the glial fibrillary acidic protein develop normally and are susceptible to scrapie prions. Neuron 14:29-41.
55. Gordon GR, Mulligan SJ, MacVicar BA (2007) Astrocyte control of the cerebrovasculature. Glia 55:1214-1221.
56. Gourine AV, Kasparov S (2011) Astrocytes as brain interoceptors. Exp Physiol 96:411-416.
57. Gourine AV, Kasymov V, Marina N, Tang F, Figueiredo MF, Lane S, Teschemacher AG, Spyer KM, Deisseroth K, Kasparov S (2010) Astrocytes control breathing through pH-dependent release of ATP. Science 329:571-575.
58. Griffin WS, Stanley LC, Ling C, White L, MacLeod V, Perrot LJ, White CL, 3rd, Araoz C (1989) Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc Natl Acad Sci USA 86:7611-7615.
59. Guenette SY (2003) Astrocytes: a cellular player in Ab clearance and degradation. Trends Mol Med 9:279-280.
60. Gurer G, Gursoy-Ozdemir Y, Erdemli E, Can A, Dalkara T (2009) Astrocytes are more resistant to focal cerebral ischemia than neurons and die by a delayed necrosis. Brain Pathol 19:630-641.
61. Hagemann TL, Connor JX, Messing A (2006) Alexander disease-associated glial fibrillary acidic protein mutations in mice induce Rosenthal fiber formation and a white matter stress response. J Neurosci 26:11162-11173.
62. Hagemann TL, Boelens WC, Wawrousek EF, Messing A (2009) Suppression of GFAP toxicity by aB-crystallin in mouse models of Alexander disease. Hum Mol Genet 18:1190-1199.
63. Halassa MM, Fellin T, Haydon PG (2007a) The tripartite synapse: roles for gliotransmission in health and disease. Trends Mol Med 13:54-63.
64. Halassa MM, Fellin T, Takano H, Dong JH, Haydon PG (2007b) Synaptic islands defined by the territory of a single astrocyte. J Neurosci 27:6473-6477.
65. Hamby ME, Sofroniew MV (2010) Reactive astrocytes as therapeutic targets for CNS disorders. Neurotherapeutics 7:494-506.
66. Hartlage-Rubsamen M, Zeitschel U, Apelt J, Gartner U, Franke H, Stahl T, Gunther A, Schliebs R, Penkowa M, Bigl V, Rossner S (2003) Astrocytic expression of the Alzheimer's disease b-secretase (BACE1) is stimulusdependent. Glia 41:169-179.
67. Harvey BK, Chang CF, Chiang YH, Bowers WJ, Morales M, Hoffer BJ, Wang Y, Federoff HJ (2003) HSV amplicon delivery of glial cell line-derived neurotrophic factor is neuroprotective against ischemic injury. Exp Neurol 183:47-55.
68. Hazell AS (2009) Astrocytes are a major target in thiamine deficiency and Wernicke's encephalopathy. Neurochem Int 55:129-135.
69. Hazell AS, Sheedy D, Oanea R, Aghourian M, Sun S, Jung JY, Wang D, Wang C (2009) Loss of astrocytic glutamate transporters in Wernicke encephalopathy. Glia 58:148-156.
70. Heneka MT, Sastre M, Dumitrescu-Ozimek L, Dewachter I, Walter J, Klockgether T, Van Leuven F (2005) Focal glial activation coincides with increased BACE1 activation and precedes amyloid plaque deposition in APP[V717I] transgenic mice. J Neuroinflam 2:22.
71. Heneka MT, Rodriguez JJ, Verkhratsky A (2010) Neuroglia in neurodegeneration. Brain Res Rev 63:189-211.
72. Hermann DM, Kilic E, Kugler S, Isenmann S, Bahr M (2001) Adenovirusmediated GDNF and CNTF pretreatment protects against striatal injury following transient middle cerebral artery occlusion in mice. Neurobiol Dis 8:655-666.
73. 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.
74. Hinterkeuser S, Schroder W, Hager G, Seifert G, Blumcke I, Elger CE, Schramm J, Steinhauser C (2000) Astrocytes in the hippocampus of patients with temporal lobe epilepsy display changes in potassium conductances. Eur J Neurosci 12:2087-2096.
75. Hsiao VC, Tian R, Long H, Der Perng M, Brenner M, Quinlan RA, Goldman JE (2005) Alexander-disease mutation of GFAP causes filament disorganization and decreased solubility of GFAP. J Cell Sci 118:2057-2065.
76. Hu J, Ferreira A, Van Eldik LJ (1997) S100b induces neuronal cell death through nitric oxide release from astrocytes. J Neurochem 69:2294-2301.
77. Huckstepp RT, id Bihi R, Eason R, Spyer KM, Dicke N, Willecke K, Marina N, Gourine AV, Dale N (2010) Connexin hemichannel-mediated CO2- dependent release of ATP in the medulla oblongata contributes to central respiratory chemosensitivity. J Physiol 588:3901-3920.
78. Iadecola C, Nedergaard M (2007) Glial regulation of the cerebral microvasculature. Nat Neurosci 10:1369-1376.
79. Ingram EM, Wiseman JW, Tessler S, Emson PC (2001) Reduction of glial glutamate transporters in the parietal cortex and hippocampus of the EL mouse. J Neurochem 79:564-575.
80. 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 46:1871-1880.
81. Jelkmann W, Wagner K (2004) Beneficial and ominous aspects of the pleiotropic action of erythropoietin. Ann Hematol 83:673-686.
82. Jian Liu K, Rosenberg GA (2005) Matrix metalloproteinases and free radicals in cerebral ischemia. Free Radic Biol Med 39:71-80.
83. Jin KL, Mao XO, Greenberg DA (2000) Vascular endothelial growth factor: direct neuroprotective effect in in vitro ischemia. Proc Natl Acad Sci USA 97:10242-10247.
84. Kano M, Hashimoto K (2009) Synapse elimination in the central nervous system. Curr Opin Neurobiol 19:154-161.
85. Kersaitis C, Halliday GM, Kril JJ (2004) Regional and cellular pathology in frontotemporal dementia: relationship to stage of disease in cases with and without Pick bodies. Acta Neuropathol 108:515-523.
86. Kettenmann H, Verkhratsky A (2008) Neuroglia: the 150 years after. Trends Neurosci 31:653-659.
87. Kitagawa H, Sasaki C, Sakai K, Mori A, Mitsumoto Y, Mori T, Fukuchi Y, Setoguchi Y, Abe K (1999) Adenovirus-mediated gene transfer of glial cell line-derived neurotrophic factor prevents ischemic brain injury after transient middle cerebral artery occlusion in rats. J Cereb Blood Flow Metab 19:1336-1344.
88. Koehler RC, Roman RJ, Harder DR (2009) Astrocytes and the regulation of cerebral blood flow. Trends Neurosci 32:160-169.
89. 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 10:719-726.
90. Kulijewicz-Nawrot M, Verkhratsky A, Chvatal A, Sykova ́ E, Rodri ́guez JJ (2011) Astrocytic morphological and functional alterations during the progression of Alzheimer's disease in the prefrontal cortex. Glia 59:S109.
91. Lalo U, Pankratov Y, Parpura V, Verkhratsky A (2011a) Ionotropic receptors in neuronal-astroglial signalling: what is the role of 'excitable' molecules in non-excitable cells. Biochim Biophys Acta 1813:992-1002.
92. Lalo U, Verkhratsky A, Pankratov Y (2011b) Ionotropic ATP receptors in neuronal-glial communication. Semin Cell Dev Biol 22:220-228.
93. Lee MY, Ju WK, Cha JH, Son BC, Chun MH, Kang JK, Park CK (1999) Expression of vascular endothelial growth factor mRNA following transient forebrain ischemia in rats. Neurosci Lett 265:107-110.
94. Lee SH, Magge S, Spencer DD, Sontheimer H, Cornell-Bell AH (1995) Human epileptic astrocytes exhibit increased gap junction coupling. Glia 15:195-202.
95. Lee TS, Mane S, Eid T, Zhao H, Lin A, Guan Z, Kim JH, Schweitzer J, King- Stevens D, Weber P, Spencer SS, Spencer DD, de Lanerolle NC (2007) Gene expression in temporal lobe epilepsy is consistent with increased release of glutamate by astrocytes. Mol Med 13:1-13.
96. 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 28:468-481.
97. Li R, Johnson AB, Salomons G, Goldman JE, Naidu S, Quinlan R, Cree B, Ruyle SZ, Banwell B, D'Hooghe M, Siebert JR, Rolf CM, Cox H, Reddy A, Gutierrez-Solana LG, Collins A, Weller RO, Messing A, van der Knaap MS, Brenner M (2005) Glial fibrillary acidic protein mutations in infantile, juvenile, and adult forms of Alexander disease. Ann Neurol 57:310-326.
98. Liauw J, Hoang S, Choi M, Eroglu C, Sun GH, Percy M, Wildman-Tobriner B, Bliss T, Guzman RG, Barres BA, Steinberg GK (2008) Thrombospondins 1 and 2 are necessary for synaptic plasticity and functional recovery after stroke. J Cereb Blood Flow Metab 28:1722-1732.
99. 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 28:681-695.
100. Lin JH, Weigel H, Cotrina ML, Liu S, Bueno E, Hansen AJ, Hansen TW, Goldman S, Nedergaard M (1998) Gap-junction-mediated propagation and amplification of cell injury. Nat Neurosci 1:494-500.
101. Liu D, Smith CL, Barone FC, Ellison JA, Lysko PG, Li K, Simpson IA (1999) Astrocytic demise precedes delayed neuronal death in focal ischemic rat brain. Brain Res Mol Brain Res 68:29-41.
102. Lobsiger CS, Cleveland DW (2007) Glial cells as intrinsic components of noncell- autonomous neurodegenerative disease. Nat Neurosci 10:1355-1360.
103. Magistretti PJ (2006) Neuron-glia metabolic coupling and plasticity. J Exp Biol 209:2304-2311.
104. Malthankar-Phatak GH, de Lanerolle N, Eid T, Spencer DD, Behar KL, Spencer SS, Kim JH, Lai JC (2006) Differential glutamate dehydrogenase (GDH) activity profile in patients with temporal lobe epilepsy. Epilepsia 47:1292-1299.
105. Marti HH, Gassmann M, Wenger RH, Kvietikova I, Morganti-Kossmann MC, Kossmann T, Trentz O, Bauer C (1997) Detection of erythropoietin in human liquor: intrinsic erythropoietin production in the brain. Kidney Int 51:416-418.
106. Masuda S, Okano M, Yamagishi K, Nagao M, Ueda M, Sasaki R (1994) A novel site of erythropoietin production. Oxygen-dependent production in cultured rat astrocytes. J Biol Chem 269:19488-19493.
107. Matsui T, Mori T, Tateishi N, Kagamiishi Y, Satoh S, Katsube N, Morikawa E, Morimoto T, Ikuta F, Asano T (2002) Astrocytic activation and delayed infarct expansion after permanent focal ischemia in rats. Part I: enhanced astrocytic synthesis of s-100b in the periinfarct area precedes delayed infarct expansion. J Cereb Blood Flow Metab 22:711-722.
108. Matthias K, Kirchhoff F, Seifert G, Huttmann K, Matyash M, Kettenmann H, Steinhauser C (2003) Segregated expression of AMPA-type glutamate receptors and glutamate transporters defines distinct astrocyte populations in the mouse hippocampus. J Neurosci 23:1750-1758.
109. McCall MA, Gregg RG, Behringer RR, Brenner M, Delaney CL, Galbreath EJ, Zhang CL, Pearce RA, Chiu SY, Messing A (1996) Targeted deletion in astrocyte intermediate filament (Gfap) alters neuronal physiology. Proc Natl Acad Sci USA 93:6361-6366.
110. McGeer PL, McGeer EG (2002) Inflammatory processes in amyotrophic lateral sclerosis. Muscle Nerve 26:459-470.
111. McGeer PL, McGeer EG (2008) Glial reactions in Parkinson's disease. Mov Disord 23:474-483.
112. Mena MA, Casarejos MJ, Carazo A, Paino CL, Garcia de Yebenes J (1996) Glia conditioned medium protects fetal rat midbrain neurones in culture from L-DOPA toxicity. Neuroreport 7:441-445.
113. Mena MA, Casarejos MJ, Garcia de Yebenes J (1999) The effect of gliaconditioned medium on dopamine neurons in culture. Modulation of apoptosis, tyrosine hydroxylase expression and 1-methyl-4-phenylpyridinium toxicity. J Neural Transm 106:1105-1123.
114. Mena MA, Garcia de Yebenes J (2008) Glial cells as players in Parkinsonism: the 'good,' the 'bad,' and the 'mysterious' glia. Neuroscientist 14:544-560.
115. Messing A, Daniels CM, Hagemann TL (2010) Strategies for treatment in Alexander disease. Neurotherapeutics 7:507-515.
116. 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 152:391-398.
117. Messing A, Li R, Naidu S, Taylor JP, Silverman L, Flint D, van der Knaap MS, Brenner M (2011) Archetypal and new families with Alexander disease and novel mutations in GFAP. Arch Neurol
118. Morishita E, Masuda S, Nagao M, Yasuda Y, Sasaki R (1997) Erythropoietin receptor is expressed in rat hippocampal and cerebral cortical neurons, and erythropoietin prevents in vitro glutamate-induced neuronal death. Neuroscience 76:105-116.
119. Mrak RE, Griffin WS (2005) Glia and their cytokines in progression of neurodegeneration. Neurobiol Aging 26:349-354.
120. 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.
121. 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 10:615-622.
122. Nagele RG, D'Andrea MR, Lee H, Venkataraman V, Wang HY (2003) Astrocytes accumulate Ab 42 and give rise to astrocytic amyloid plaques in Alzheimer disease brains. Brain Res 971:197-209.
123. 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 25:663-674.
124. Nedergaard M, Dirnagl U (2005) Role of glial cells in cerebral ischemia. Glia 50:281-286.
125. Nedergaard M, Ransom B, Goldman SA (2003) New roles for astrocytes: redefining the functional architecture of the brain. Trends Neurosci 26:523-530.
126. Nedergaard M, Rodriguez JJ, Verkhratsky A (2010) Glial calcium and diseases of the nervous system. Cell Calcium 47:140-149.
127. Nedergaard M, Verkhratsky A (2012) Artifact versus reality-How astrocytes contribute to synaptic events? Glia, doi:10.1002/glia.22288 Newman EA (1995) Glial cell regulation of extracellular potassium. In Neuroglia (Kettenmann H, Ransom B, eds), pp 717-731, Oxford University Press, New York.
128. Nicoll JA, Weller RO (2003) A new role for astrocytes: b-amyloid homeostasis and degradation. Trends Mol Med 9:281-282.
129. Nudo RJ (2007) Postinfarct cortical plasticity and behavioral recovery. Stroke 38:840-845.
130. O'Connor ER, Sontheimer H, Spencer DD, de Lanerolle NC (1998) Astrocytes from human hippocampal epileptogenic foci exhibit action potential-like responses. Epilepsia 39:347-354.
131. 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 28:3264-3276.
132. Oberheim NA, Wang X, Goldman S, Nedergaard M (2006) Astrocytic complexity distinguishes the human brain. Trends Neurosci 29:547-553.
133. Ogata K, Kosaka T (2002) Structural and quantitative analysis of astrocytes in the mouse hippocampus. Neuroscience 113:221-233.
134. 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. Nat Med 12:829-834.
135. Olabarria M, Noristani HN, Verkhratsky A, Rodriguez JJ (2010) Concomitant astroglial atrophy and astrogliosis in a triple transgenic animal model of Alzheimer's disease. Glia 58:831-838.
136. Olabarria M, Noristani HN, Verkhratsky A, Rodriguez JJ (2011) Age-dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic Alzheimer's disease mouse model: mechanism for deficient glutamatergic transmission? Mol Neurodegener 6:55.
137. 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 14:1590-1598.
138. Pekny M, Nilsson M (2005) Astrocyte activation and reactive gliosis. Glia 50:427-434.
139. Penfield W, Humphreys S (1940) Epileptogenic lesions of the brain. A histologic study. Arch Neurol Psychiatry 43:240-259.
140. Perea G, Navarrete M, Araque A (2009) Tripartite synapses: astrocytes process and control synaptic information. Trends Neurosci 32:421-431.
141. Perng MD, Wen SF, Gibbon T, Middeldorp J, Sluijs J, Hol EM, Quinlan RA (2008) Glial fibrillary acidic protein filaments can tolerate the incorporation of assembly-compromised GFAP-d, but with consequences for filament organization and aB-crystallin association. Mol Biol Cell 19:4521-4533.
142. Pfrieger FW (2009) Roles of glial cells in synapse development. Cell Mol Life Sci 66:2037-2047.
143. Potts R, Leech RW (2005) Thalamic dementia: an example of primary astroglial dystrophy of Seitelberger. Clin Neuropathol 24:271-275.
144. Prass K, Scharff A, Ruscher K, Lowl D, Muselmann C, Victorov I, Kapinya K, Dirnagl U, Meisel A (2003) Hypoxia-induced stroke tolerance in the mouse is mediated by erythropoietin. Stroke 34:1981-1986.
145. Prust M, Wang J, Morizono H, Messing A, Brenner M, Gordon E, Hartka T, Sokohl A, Schiffmann R, Gordish-Dressman H, Albin R, Amartino H, Brockman K, Dinopoulos A, Dotti MT, Fain D, Fernandez R, Ferreira J, Fleming J, Gill D, Griebel M, Heilstedt H, Kaplan P, Lewis D, Nakagawa M, Pedersen R, Reddy A, Sawaishi Y, Schneider M, Sherr E, Takiyama Y, Wakabayashi K, Gorospe JR, Vanderver A (2011) GFAP mutations, age at onset, and clinical subtypes in Alexander disease. Neurology 77:1287-1294.
146. Rao KV, Panickar KS, Jayakumar AR, Norenberg MD (2005) Astrocytes protect neurons from ammonia toxicity. Neurochem Res 30:1311-1318.
147. Reichenbach A, Wolburg H (2005) Astrocytes and ependymal glia. In Neuroglia (Kettenmann H, Ransom BR, eds), pp 19-35, Oxford University Press, Oxford.
148. Rodriguez JJ, Olabarria M, Chvatal A, Verkhratsky A (2009) Astroglia in dementia and Alzheimer's disease. Cell Death Differ 16:378-385.
149. Rodriguez JJ, Verkhratsky A (2011) Neuroglial roots of neurodegenerative diseases? Mol Neurobiol 43:87-96.
150. Rossi D, Brambilla L, Valori CF, Roncoroni C, Crugnola A, Yokota T, Bredesen DE, Volterra A (2008) Focal degeneration of astrocytes in amyotrophic lateral sclerosis. Cell Death Differ 15:1691-1700.