Astrocytes, therapeutic targets for neuroprotection and neurorestoration in ischemic stroke

Progress in Neurobiology

Volumn 144, Issue , 2016, Pages 103-120

  Liu, Zhongwu ^a   Chopp, Michael ^a,b  

^a HENRY FORD HOSPITAL   (United States)

^b OAKLAND UNIVERSITY   (United States)

Author keywords

Astrocytes; Neuroprotection; Neurorestoration; Stroke

Indexed keywords

ANTIOXIDANT; CARNOSINE; ERYTHROPOIETIN; GLUTAMIC ACID; GROWTH FACTOR; NEUROPROTECTIVE AGENT; NEUROTROPHIN; TAMOXIFEN;

ANGIOGENESIS; ASTROCYTE; ASTROCYTOSIS; BLOOD BRAIN BARRIER; BRAIN ISCHEMIA; CELL ACTIVATION; CELL THERAPY; EXCITOTOXICITY; GAP JUNCTION; HUMAN; NERVE CELL PLASTICITY; NERVOUS SYSTEM DEVELOPMENT; NEUROPROTECTION; NONHUMAN; PRIORITY JOURNAL; REVIEW; SCAR FORMATION; SYNAPSE; SYNAPTOGENESIS; ANIMAL; METABOLISM; NERVE REGENERATION; PHYSIOLOGY; STROKE;

ANIMALS; ASTROCYTES; BRAIN ISCHEMIA; HUMANS; NERVE REGENERATION; NEUROPROTECTION; STROKE;

EID: 84952837207     PISSN: 03010082     EISSN: 18735118     Source Type: Journal    
DOI: 10.1016/j.pneurobio.2015.09.008     Document Type: Review

References (333)

1. Abbott, N.J., Ronnback, L., Hansson, E., Astrocyte-endothelial interactions at the blood–brain barrier. Nat. Rev. Neurosci. 7 (2006), 41–53.
2. Abe, K., Therapeutic potential of neurotrophic factors and neural stem cells against ischemic brain injury. J. Cereb. Blood Flow Metab. 20 (2000), 1393–1408.
3. Addis, R.C., Hsu, F.C., Wright, R.L., Dichter, M.A., Coulter, D.A., Gearhart, J.D., Efficient conversion of astrocytes to functional midbrain dopaminergic neurons using a single polycistronic vector. PLoS ONE, 6, 2011, e28719.
4. Akaneya, Y., Tsumoto, T., Kinoshita, S., Hatanaka, H., Brain-derived neurotrophic factor enhances long-term potentiation in rat visual cortex. J. Neurosci. 17 (1997), 6707–6716.
5. Allen, N.J., Bennett, M.L., Foo, L.C., Wang, G.X., Chakraborty, C., Smith, S.J., Barres, B.A., Astrocyte glypicans 4 and 6 promote formation of excitatory synapses via GluA1 AMPA receptors. Nature 486 (2012), 410–414.
6. Almeida, A., Delgado-Esteban, M., Bolanos, J.P., Medina, J.M., Oxygen and glucose deprivation induces mitochondrial dysfunction and oxidative stress in neurones but not in astrocytes in primary culture. J. Neurochem. 81 (2002), 207–217.
7. Alvarez, J.I., Dodelet-Devillers, A., Kebir, H., Ifergan, I., Fabre, P.J., Terouz, S., Sabbagh, M., Wosik, K., Bourbonniere, L., Bernard, M., van Horssen, J., de Vries, H.E., Charron, F., Prat, A., The Hedgehog pathway promotes blood–brain barrier integrity and CNS immune quiescence. Science 334 (2011), 1727–1731.
8. Anderson, C.M., Swanson, R.A., Astrocyte glutamate transport: review of properties, regulation, and physiological functions. Glia 32 (2000), 1–14.
9. Araque, A., Parpura, V., Sanzgiri, R.P., Haydon, P.G., Tripartite synapses: glia, the unacknowledged partner. Trends Neurosci. 22 (1999), 208–215.
10. Arvidsson, A., Collin, T., Kirik, D., Kokaia, Z., Lindvall, O., Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat. Med. 8 (2002), 963–970.
11. Asada, H., Ip, N.Y., Pan, L., Razack, N., Parfitt, M.M., Plunkett, R.J., Time course of ciliary neurotrophic factor mRNA expression is coincident with the presence of protoplasmic astrocytes in traumatized rat striatum. J. Neurosci. Res. 40 (1995), 22–30.
12. Attwell, D., Buchan, A.M., Charpak, S., Lauritzen, M., Macvicar, B.A., Newman, E.A., Glial and neuronal control of brain blood flow. Nature 468 (2010), 232–243.
13. Auguste, K.I., Jin, S., Uchida, K., Yan, D., Manley, G.T., Papadopoulos, M.C., Verkman, A.S., Greatly impaired migration of implanted aquaporin-4-deficient astroglial cells in mouse brain toward a site of injury. FASEB J. 21 (2007), 108–116 (official publication of the Federation of American Societies for Experimental Biology).
14. Ballabh, P., Braun, A., Nedergaard, M., The blood–brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol. Dis. 16 (2004), 1–13.
15. Bao, Y., Qin, L., Kim, E., Bhosle, S., Guo, H., Febbraio, M., Haskew-Layton, R.E., Ratan, R., Cho, S., CD36 is involved in astrocyte activation and astroglial scar formation. J. Cereb. Blood Flow Metab. 32 (2012), 1567–1577.
16. Basic Kes, V., Simundic, A.M., Nikolac, N., Topic, E., Demarin, V., Pro-inflammatory and anti-inflammatory cytokines in acute ischemic stroke and their relation to early neurological deficit and stroke outcome. Clin. Biochem. 41 (2008), 1330–1334.
17. Baydas, G., Reiter, R.J., Nedzvetskii, V.S., Yasar, A., Tuzcu, M., Ozveren, F., Canatan, H., Melatonin protects the central nervous system of rats against toluene-containing thinner intoxication by reducing reactive gliosis. Toxicol. Lett. 137 (2003), 169–174.
18. Bejot, Y., Prigent-Tessier, A., Cachia, C., Giroud, M., Mossiat, C., Bertrand, N., Garnier, P., Marie, C., Time-dependent contribution of non neuronal cells to BDNF production after ischemic stroke in rats. Neurochem. Int. 58 (2011), 102–111.
19. Bergami, M., Santi, S., Formaggio, E., Cagnoli, C., Verderio, C., Blum, R., Berninger, B., Matteoli, M., Canossa, M., Uptake and recycling of pro-BDNF for transmitter-induced secretion by cortical astrocytes. J. Cell Biol. 183 (2008), 213–221.
20. Bernaudin, M., Bellail, A., Marti, H.H., Yvon, A., Vivien, D., Duchatelle, I., Mackenzie, E.T., Petit, E., Neurons and astrocytes express EPO mRNA: oxygen-sensing mechanisms that involve the redox-state of the brain. Glia 30 (2000), 271–278.
21. Bernaudin, M., Tang, Y., Reilly, M., Petit, E., Sharp, F.R., Brain genomic response following hypoxia and re-oxygenation in the neonatal rat. Identification of genes that might contribute to hypoxia-induced ischemic tolerance. J. Biol. Chem. 277 (2002), 39728–39738.
22. Berninger, B., Costa, M.R., Koch, U., Schroeder, T., Sutor, B., Grothe, B., Gotz, M., Functional properties of neurons derived from in vitro reprogrammed postnatal astroglia. J. Neurosci. 27 (2007), 8654–8664.
23. Bidmon, H.J., Jancsik, V., Schleicher, A., Hagemann, G., Witte, O.W., Woodhams, P., Zilles, K., Structural alterations and changes in cytoskeletal proteins and proteoglycans after focal cortical ischemia. Neuroscience 82 (1998), 397–420.
24. 2+ homeostasis and cell death. J. Neurochem. 70 (1998), 958–970.
25. Blum, R., Heinrich, C., Sanchez, R., Lepier, A., Gundelfinger, E.D., Berninger, B., Gotz, M., Neuronal network formation from reprogrammed early postnatal rat cortical glial cells. Cereb. Cortex 21 (2011), 413–424.
26. Brunello, A.G., Weissenberger, J., Kappeler, A., Vallan, C., Peters, M., Rose-John, S., Weis, J., Astrocytic alterations in interleukin-6/soluble interleukin-6 receptor alpha double-transgenic mice. Am. J. Pathol. 157 (2000), 1485–1493.
27. Bush, T.G., Puvanachandra, N., Horner, C.H., Polito, A., Ostenfeld, T., Svendsen, C.N., Mucke, L., Johnson, M.H., Sofroniew, M.V., Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice. Neuron 23 (1999), 297–308.
28. Buskila, Y., Farkash, S., Hershfinkel, M., Amitai, Y., Rapid and reactive nitric oxide production by astrocytes in mouse neocortical slices. Glia 52 (2005), 169–176.
29. Cardenas, H., Bolin, L.M., Compromised reactive microgliosis in MPTP-lesioned IL-6 KO mice. Brain Res. 985 (2003), 89–97.
30. Carmichael, S.T., Cellular and molecular mechanisms of neural repair after stroke: making waves. Ann. Neurol. 59 (2006), 735–742.
31. Catania, M.V., Giuffrida, R., Seminara, G., Barbagallo, G., Aronica, E., Gorter, J.A., Dell'Albani, P., Ravagna, A., Calabrese, V., Giuffrida-Stella, A.M., Upregulation of neuronal nitric oxide synthase in in vitro stellate astrocytes and in vivo reactive astrocytes after electrically induced status epilepticus. Neurochem. Res. 28 (2003), 607–615.
32. Cekanaviciute, E., Fathali, N., Doyle, K.P., Williams, A.M., Han, J., Buckwalter, M.S., Astrocytic transforming growth factor-beta signaling reduces subacute neuroinflammation after stroke in mice. Glia 62 (2014), 1227–1240.
33. Chen, J., Li, Y., Wang, L., Zhang, Z., Lu, D., Lu, M., Chopp, M., Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke 32 (2001), 1005–1011 (a journal of cerebral circulation).
34. Chen, J., Li, Y., Zhang, R., Katakowski, M., Gautam, S.C., Xu, Y., Lu, M., Zhang, Z., Chopp, M., Combination therapy of stroke in rats with a nitric oxide donor and human bone marrow stromal cells enhances angiogenesis and neurogenesis. Brain Res. 1005 (2004), 21–28.
35. Chen, J., Sanberg, P.R., Li, Y., Wang, L., Lu, M., Willing, A.E., Sanchez-Ramos, J., Chopp, M., Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats. Stroke 32 (2001), 2682–2688 (a journal of cerebral circulation).
36. Chen, Y., Swanson, R.A., Astrocytes and brain injury. J. Cereb. Blood Flow Metab. 23 (2003), 137–149.
37. Chen, Y., Vartiainen, N.E., Ying, W., Chan, P.H., Koistinaho, J., Swanson, R.A., Astrocytes protect neurons from nitric oxide toxicity by a glutathione-dependent mechanism. J. Neurochem. 77 (2001), 1601–1610.
38. Chiang, C.S., Stalder, A., Samimi, A., Campbell, I.L., Reactive gliosis as a consequence of interleukin-6 expression in the brain: studies in transgenic mice. Dev. Neurosci. 16 (1994), 212–221.
39. Cho, K.S., Yang, L., Lu, B., Feng Ma, H., Huang, X., Pekny, M., Chen, D.F., Re-establishing the regenerative potential of central nervous system axons in postnatal mice. J. Cell Sci. 118 (2005), 863–872.
40. Cho, S., Park, E.M., Febbraio, M., Anrather, J., Park, L., Racchumi, G., Silverstein, R.L., Iadecola, C., The class B scavenger receptor CD36 mediates free radical production and tissue injury in cerebral ischemia. J. Neurosci. 25 (2005), 2504–2512.
41. Choi, D.W., Glutamate neurotoxicity and diseases of the nervous system. Neuron 1 (1988), 623–634.
42. Chopp, M., Li, Y., Treatment of neural injury with marrow stromal cells. Lancet Neurol. 1 (2002), 92–100.
43. Christopherson, K.S., Ullian, E.M., Stokes, C.C., Mullowney, C.E., Hell, J.W., Agah, A., Lawler, J., Mosher, D.F., Bornstein, P., Barres, B.A., Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis. Cell 120 (2005), 421–433.
44. Chu, K., Lee, S.T., Sinn, D.I., Ko, S.Y., Kim, E.H., Kim, J.M., Kim, S.J., Park, D.K., Jung, K.H., Song, E.C., Lee, S.K., Kim, M., Roh, J.K., Pharmacological induction of ischemic tolerance by glutamate transporter-1 (EAAT2) upregulation. Stroke 38 (2007), 177–182 (a journal of cerebral circulation).
45. Cina, C., Maass, K., Theis, M., Willecke, K., Bechberger, J.F., Naus, C.C., Involvement of the cytoplasmic C-terminal domain of connexin43 in neuronal migration. J. Neurosci. 29 (2009), 2009–2021.
46. Clarke, S.R., Shetty, A.K., Bradley, J.L., Turner, D.A., Reactive astrocytes express the embryonic intermediate neurofilament nestin. NeuroReport 5 (1994), 1885–1888.
47. Colell, A., Garcia-Ruiz, C., Miranda, M., Ardite, E., Mari, M., Morales, A., Corrales, F., Kaplowitz, N., Fernandez-Checa, J.C., Selective glutathione depletion of mitochondria by ethanol sensitizes hepatocytes to tumor necrosis factor. Gastroenterology 115 (1998), 1541–1551.
48. Cornell-Bell, A.H., Thomas, P.G., Smith, S.J., The excitatory neurotransmitter glutamate causes filopodia formation in cultured hippocampal astrocytes. Glia 3 (1990), 322–334.
49. Cotrina, M.L., Kang, J., Lin, J.H., Bueno, E., Hansen, T.W., He, L., Liu, Y., Nedergaard, M., Astrocytic gap junctions remain open during ischemic conditions. J. Neurosci. 18 (1998), 2520–2537.
50. Cramer, S.C., Chopp, M., Recovery recapitulates ontogeny. Trends Neurosci. 23 (2000), 265–271.
51. Cunningham, L.A., Wetzel, M., Rosenberg, G.A., Multiple roles for MMPs and TIMPs in cerebral ischemia. Glia 50 (2005), 329–339.
52. Daneman, R., Prat, A., The blood–brain barrier. Cold Spring Harbor Perspect. Biol., 7, 2015, a020412.
53. Daskalopoulos, R., Korcok, J., Tao, L., Wilson, J.X., Accumulation of intracellular ascorbate from dehydroascorbic acid by astrocytes is decreased after oxidative stress and restored by propofol. Glia 39 (2002), 124–132.
54. de Pablo, Y., Nilsson, M., Pekna, M., Pekny, M., Intermediate filaments are important for astrocyte response to oxidative stress induced by oxygen-glucose deprivation and reperfusion. Histochem. Cell Biol. 140 (2013), 81–91.
55. del Zoppo, G.J., Hallenbeck, J.M., Advances in the vascular pathophysiology of ischemic stroke. Thrombosis Res. 98 (2000), 73–81.
56. Ding, M., Eliasson, C., Betsholtz, C., Hamberger, A., Pekny, M., Altered taurine release following hypotonic stress in astrocytes from mice deficient for GFAP and vimentin. Brain Res. Mol. Brain Res. 62 (1998), 77–81.
57. Ding, X., Li, Y., Liu, Z., Zhang, J., Cui, Y., Chen, X., Chopp, M., The sonic hedgehog pathway mediates brain plasticity and subsequent functional recovery after bone marrow stromal cell treatment of stroke in mice. J. Cereb. Blood Flow Metab. 33 (2013), 1015–1024.
58. Doetsch, F., Caille, I., Lim, D.A., Garcia-Verdugo, J.M., Alvarez-Buylla, A., Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97 (1999), 703–716.
59. Dringen, R., Metabolism and functions of glutathione in brain. Prog. Neurobiol. 62 (2000), 649–671.
60. Dringen, R., Pfeiffer, B., Hamprecht, B., Synthesis of the antioxidant glutathione in neurons: supply by astrocytes of CysGly as precursor for neuronal glutathione. J. Neurosci. 19 (1999), 562–569.
61. Duncan, P.W., Zorowitz, R., Bates, B., Choi, J.Y., Glasberg, J.J., Graham, G.D., Katz, R.C., Lamberty, K., Reker, D., Management of adult stroke rehabilitation care: a clinical practice guideline. Stroke 36 (2005), e100–e143 (a journal of cerebral circulation).
62. Dvoriantchikova, G., Barakat, D., Brambilla, R., Agudelo, C., Hernandez, E., Bethea, J.R., Shestopalov, V.I., Ivanov, D., Inactivation of astroglial NF-kappa B promotes survival of retinal neurons following ischemic injury. Eur. J. Neurosci. 30 (2009), 175–185.
63. Ehrenreich, H., Weissenborn, K., Prange, H., Schneider, D., Weimar, C., Wartenberg, K., Schellinger, P.D., 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., Group, E.P.O.S.T, Recombinant human erythropoietin in the treatment of acute ischemic stroke. Stroke 40 (2009), e647–e656 (a journal of cerebral circulation).
64. Endoh, M., Maiese, K., Wagner, J., Expression of the inducible form of nitric oxide synthase by reactive astrocytes after transient global ischemia. Brain Res. 651 (1994), 92–100.
65. Ezan, P., Andre, P., Cisternino, S., Saubamea, B., Boulay, A.C., Doutremer, S., Thomas, M.A., Quenech'du, N., Giaume, C., Cohen-Salmon, M., Deletion of astroglial connexins weakens the blood–brain barrier. J. Cereb. Blood Flow Metab. 32 (2012), 1457–1467.
66. Fang, M.C., Cutler, D.M., Rosen, A.B., Trends in thrombolytic use for ischemic stroke in the United States. J. Hosp. Med. 5 (2010), 406–409.
67. Fang, S.H., Wei, E.Q., Zhou, Y., Wang, M.L., Zhang, W.P., Yu, G.L., Chu, L.S., Chen, Z., Increased expression of cysteinyl leukotriene receptor-1 in the brain mediates neuronal damage and astrogliosis after focal cerebral ischemia in rats. Neuroscience 140 (2006), 969–979.
68. Faulkner, J.R., Herrmann, J.E., Woo, M.J., Tansey, K.E., Doan, N.B., Sofroniew, M.V., Reactive astrocytes protect tissue and preserve function after spinal cord injury. J. Neurosci. 24 (2004), 2143–2155.
69. Fellin, T., Pascual, O., Gobbo, S., Pozzan, T., Haydon, P.G., Carmignoto, G., Neuronal synchrony mediated by astrocytic glutamate through activation of extrasynaptic NMDA receptors. Neuron 43 (2004), 729–743.
70. Fitch, M.T., Silver, J., CNS injury, glial scars, and inflammation: inhibitory extracellular matrices and regeneration failure. Exp. Neurol. 209 (2008), 294–301.
71. Frantseva, M.V., Kokarovtseva, L., Perez Velazquez, J.L., Ischemia-induced brain damage depends on specific gap-junctional coupling. J. Cereb. Blood Flow Metab. 22 (2002), 453–462.
72. Frautschy, S.A., Walicke, P.A., Baird, A., Localization of basic fibroblast growth factor and its mRNA after CNS injury. Brain Res. 553 (1991), 291–299.
73. Fruhbeis, C., Frohlich, D., Kuo, W.P., Kramer-Albers, E.M., Extracellular vesicles as mediators of neuron–glia communication. Front. Cell. Neurosci., 7, 2013, 182.
74. Fuchs, E., Cleveland, D.W., A structural scaffolding of intermediate filaments in health and disease. Science 279 (1998), 514–519.
75. Fukuda, A.M., Badaut, J., Aquaporin 4: a player in cerebral edema and neuroinflammation. J. Neuroinflamm., 9, 2012, 279.
76. Fukuda, A.M., Pop, V., Spagnoli, D., Ashwal, S., Obenaus, A., Badaut, J., Delayed increase of astrocytic aquaporin 4 after juvenile traumatic brain injury: possible role in edema resolution?. Neuroscience 222 (2012), 366–378.
77. Furukawa, S., Furukawa, Y., Satoyoshi, E., Hayashi, K., Synthesis/secretion of nerve growth factor is associated with cell growth in cultured mouse astroglial cells. Biochem. Biophys. Res. Commun. 142 (1987), 395–402.
78. Gakhar-Koppole, N., Hundeshagen, P., Mandl, C., Weyer, S.W., Allinquant, B., Muller, U., Ciccolini, F., Activity requires soluble amyloid precursor protein alpha to promote neurite outgrowth in neural stem cell-derived neurons via activation of the MAPK pathway. Eur. J. Neurosci. 28 (2008), 871–882.
79. Gao, Q., Katakowski, M., Chen, X., Li, Y., Chopp, M., Human marrow stromal cells enhance connexin43 gap junction intercellular communication in cultured astrocytes. Cell Transplant. 14 (2005), 109–117.
80. Gao, Q., Li, Y., Chopp, M., Bone marrow stromal cells increase astrocyte survival via upregulation of phosphoinositide 3-kinase/threonine protein kinase and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathways and stimulate astrocyte trophic factor gene expression after anaerobic insult. Neuroscience 136 (2005), 123–134.
81. Gardner-Medwin, A.R., Analysis of potassium dynamics in mammalian brain tissue. J. Physiol. 335 (1983), 393–426.
82. Giaume, C., Liu, X., From a glial syncytium to a more restricted and specific glial networking. J. Physiol. 106 (2012), 34–39 (Paris).
83. Giaume, C., McCarthy, K.D., Control of gap-junctional communication in astrocytic networks. Trends Neurosci. 19 (1996), 319–325.
84. Giordano, G., Kavanagh, T.J., Costa, L.G., Mouse cerebellar astrocytes protect cerebellar granule neurons against toxicity of the polybrominated diphenyl ether (PBDE) mixture DE-71. Neurotoxicology 30 (2009), 326–329.
85. Goldberg, M.P., Choi, D.W., Combined oxygen and glucose deprivation in cortical cell culture: calcium-dependent and calcium-independent mechanisms of neuronal injury. J. Neurosci. 13 (1993), 3510–3524.
86. Gordon, G.R., Howarth, C., MacVicar, B.A., Bidirectional control of arteriole diameter by astrocytes. Exp. Physiol. 96 (2011), 393–399.
87. Gordon, G.R., Mulligan, S.J., MacVicar, B.A., Astrocyte control of the cerebrovasculature. Glia 55 (2007), 1214–1221.
88. Gris, P., Tighe, A., Levin, D., Sharma, R., Brown, A., Transcriptional regulation of scar gene expression in primary astrocytes. Glia 55 (2007), 1145–1155.
89. Gunnarson, E., Song, Y., Kowalewski, J.M., Brismar, H., Brines, M., Cerami, A., Andersson, U., Zelenina, M., Aperia, A., Erythropoietin modulation of astrocyte water permeability as a component of neuroprotection. Proc. Natl. Acad. Sci. U.S.A. 106 (2009), 1602–1607.
90. Guo, Z., Zhang, L., Wu, Z., Chen, Y., Wang, F., Chen, G., In vivo direct reprogramming of reactive glial cells into functional neurons after brain injury and in an Alzheimer's disease model. Cell Stem Cell 14 (2014), 188–202.
91. Gurer, G., Gursoy-Ozdemir, Y., Erdemli, E., Can, A., Dalkara, T., Astrocytes are more resistant to focal cerebral ischemia than neurons and die by a delayed necrosis. Brain Pathol. 19 (2009), 630–641.
92. Gursoy-Ozdemir, Y., Can, A., Dalkara, T., Reperfusion-induced oxidative/nitrative injury to neurovascular unit after focal cerebral ischemia. Stroke 35 (2004), 1449–1453 (a journal of cerebral circulation).
93. Haber, M., Zhou, L., Murai, K.K., Cooperative astrocyte and dendritic spine dynamics at hippocampal excitatory synapses. J. Neurosci. 26 (2006), 8881–8891.
94. Halassa, M.M., Fellin, T., Haydon, P.G., The tripartite synapse: roles for gliotransmission in health and disease. Trends Mol Med. 13 (2007), 54–63.
95. Han, X., Chen, M., Wang, F., Windrem, M., Wang, S., Shanz, S., Xu, Q., Oberheim, N.A., Bekar, L., Betstadt, S., Silva, A.J., Takano, T., Goldman, S.A., Nedergaard, M., Forebrain engraftment by human glial progenitor cells enhances synaptic plasticity and learning in adult mice. Cell Stem Cell 12 (2013), 342–353.
96. Hansson, E., Ronnback, L., Glial neuronal signaling in the central nervous system. FASEB J. 17 (2003), 341–348 (official publication of the Federation of American Societies for Experimental Biology).
97. Hayakawa, K., Nakano, T., Irie, K., Higuchi, S., Fujioka, M., Orito, K., Iwasaki, K., Jin, G., Lo, E.H., Mishima, K., Fujiwara, M., Inhibition of reactive astrocytes with fluorocitrate retards neurovascular remodeling and recovery after focal cerebral ischemia in mice. J. Cereb. Blood Flow Metab. 30 (2010), 871–882.
98. Hayakawa, K., Pham, L.D., Katusic, Z.S., Arai, K., Lo, E.H., Astrocytic high-mobility group box 1 promotes endothelial progenitor cell-mediated neurovascular remodeling during stroke recovery. Proc. Natl. Acad. Sci. U.S.A. 109 (2012), 7505–7510.
99. Haydon, P.G., GLIA: listening and talking to the synapse. Nature reviews. Neuroscience 2 (2001), 185–193.
100. He, Q.W., Xia, Y.P., Chen, S.C., Wang, Y., Huang, M., Huang, Y., Li, J.Y., Li, Y.N., Gao, Y., Mao, L., Mei, Y.W., Hu, B., Astrocyte-derived sonic hedgehog contributes to angiogenesis in brain microvascular endothelial cells via RhoA/ROCK pathway after oxygen-glucose deprivation. Mol. Meurobiol. 47 (2013), 976–987.
101. Heinrich, C., Blum, R., Gascon, S., Masserdotti, G., Tripathi, P., Sanchez, R., Tiedt, S., Schroeder, T., Gotz, M., Berninger, B., Directing astroglia from the cerebral cortex into subtype specific functional neurons. PLoS Biol., 8, 2010, e1000373.
102. Heinrich, C., Gotz, M., Berninger, B., Reprogramming of postnatal astroglia of the mouse neocortex into functional, synapse-forming neurons. Methods Mol. Biol. 814 (2012), 485–498.
103. Heins, N., Malatesta, P., Cecconi, F., Nakafuku, M., Tucker, K.L., Hack, M.A., Chapouton, P., Barde, Y.A., Gotz, M., Glial cells generate neurons: the role of the transcription factor Pax6. Nat. Neurosci. 5 (2002), 308–315.
104. Herx, L.M., Yong, V.W., Interleukin-1 beta is required for the early evolution of reactive astrogliosis following CNS lesion. J. Neuropathol. Exp. Neurol. 60 (2001), 961–971.
105. Hill, J.J., Jin, K., Mao, X.O., Xie, L., Greenberg, D.A., Intracerebral chondroitinase ABC and heparan sulfate proteoglycan glypican improve outcome from chronic stroke in rats. Proc. Natl. Acad. Sci. U.S.A. 109 (2012), 9155–9160.
106. Ho, A., Blum, M., Regulation of astroglial-derived dopaminergic neurotrophic factors by interleukin-1 beta in the striatum of young and middle-aged mice. Exp. Neurol. 148 (1997), 348–359.
107. Hodges-Savola, C., Rogers, S.D., Ghilardi, J.R., Timm, D.R., Mantyh, P.W., Beta-adrenergic receptors regulate astrogliosis and cell proliferation in the central nervous system in vivo. Glia 17 (1996), 52–62.
108. Holmin, S., Almqvist, P., Lendahl, U., Mathiesen, T., Adult nestin-expressing subependymal cells differentiate to astrocytes in response to brain injury. Eur. J. Neurosci. 9 (1997), 65–75.
109. Huang, J., Agus, D.B., Winfree, C.J., Kiss, S., Mack, W.J., McTaggart, R.A., Choudhri, T.F., Kim, L.J., Mocco, J., Pinsky, D.J., Fox, W.D., Israel, R.J., Boyd, T.A., Golde, D.W., Connolly, E.S. Jr., Dehydroascorbic acid, a blood–brain barrier transportable form of vitamin C, mediates potent cerebroprotection in experimental stroke. Proc. Natl. Acad. Sci. U.S.A. 98 (2001), 11720–11724.
110. Huang, Z.G., Xue, D., Preston, E., Karbalai, H., Buchan, A.M., Biphasic opening of the blood–brain barrier following transient focal ischemia: effects of hypothermia. Can. J. Neurol. Sci. (Trans.) Le journal canadien des sciences neurologiques, 26, 1999, 298–304.
111. Hyder, C.L., Isoniemi, K.O., Torvaldson, E.S., Eriksson, J.E., Insights into intermediate filament regulation from development to ageing. J. Cell Sci. 124 (2011), 1363–1372.
112. Iadecola, C., Nedergaard, M., Glial regulation of the cerebral microvasculature. Nat. Neurosci. 10 (2007), 1369–1376.
113. Imitola, J., Raddassi, K., Park, K.I., Mueller, F.J., Nieto, M., Teng, Y.D., Frenkel, D., Li, J., Sidman, R.L., Walsh, C.A., Snyder, E.Y., Khoury, S.J., Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1alpha/CXC chemokine receptor 4 pathway. Proc. Natl. Acad. Sci. U.S.A. 101 (2004), 18117–18122.
114. Jain, R.K., Molecular regulation of vessel maturation. Nat. Med. 9 (2003), 685–693.
115. Jin, K., Minami, M., Lan, J.Q., Mao, X.O., Batteur, S., Simon, R.P., Greenberg, D.A., Neurogenesis in dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat. Proc. Natl. Acad. Sci. U.S.A. 98 (2001), 4710–4715.
116. Jin, K., Sun, Y., Xie, L., Peel, A., Mao, X.O., Batteur, S., Greenberg, D.A., Directed migration of neuronal precursors into the ischemic cerebral cortex and striatum. Mol. Cell. Neurosci. 24 (2003), 171–189.
117. Jourdain, P., Bergersen, L.H., Bhaukaurally, K., Bezzi, P., Santello, M., Domercq, M., Matute, C., Tonello, F., Gundersen, V., Volterra, A., Glutamate exocytosis from astrocytes controls synaptic strength. Nat. Neurosci. 10 (2007), 331–339.
118. Joyce, N., Annett, G., Wirthlin, L., Olson, S., Bauer, G., Nolta, J.A., Mesenchymal stem cells for the treatment of neurodegenerative disease. Regener. Med. 5 (2010), 933–946.
119. Junier, M.P., Coulpier, M., Le Forestier, N., Cadusseau, J., Suzuki, F., Peschanski, M., Dreyfus, P.A., Transforming growth factor alpha (TGF alpha) expression in degenerating motoneurons of the murine mutant wobbler: a neuronal signal for astrogliosis?. J. Neurosci. 14 (1994), 4206–4216.
120. Justicia, C., Perez-Asensio, F.J., Burguete, M.C., Salom, J.B., Planas, A.M., Administration of transforming growth factor-alpha reduces infarct volume after transient focal cerebral ischemia in the rat. J. Cereb. Blood Flow Metab. 21 (2001), 1097–1104.
121. Kader, A., Frazzini, V.I., Solomon, R.A., Trifiletti, R.R., Nitric oxide production during focal cerebral ischemia in rats. Stroke 24 (1993), 1709–1716 (a journal of cerebral circulation).
122. Kajihara, H., Tsutsumi, E., Kinoshita, A., Nakano, J., Takagi, K., Takeo, S., Activated astrocytes with glycogen accumulation in ischemic penumbra during the early stage of brain infarction: immunohistochemical and electron microscopic studies. Brain Res. 909 (2001), 92–101.
123. Kaplan, M.S., Hinds, J.W., Neurogenesis in the adult rat: electron microscopic analysis of light radioautographs. Science 197 (1977), 1092–1094.
124. Kim, J.B., Lim, C.M., Yu, Y.M., Lee, J.K., Induction and subcellular localization of high-mobility group box-1 (HMGB1) in the postischemic rat brain. J. Neurosci. Res. 86 (2008), 1125–1131.
125. Kimelberg, H.K., Astrocytic swelling in cerebral ischemia as a possible cause of injury and target for therapy. Glia 50 (2005), 389–397.
126. Kimelberg, H.K., Feustel, P.J., Jin, Y., Paquette, J., Boulos, A., Keller, R.W. Jr., Tranmer, B.I., Acute treatment with tamoxifen reduces ischemic damage following middle cerebral artery occlusion. NeuroReport 11 (2000), 2675–2679.
127. Kinoshita, A., Yamada, K., Kohmura, E., Hayakawa, T., Effect of astrocyte-derived factors on ischemic brain edema induced by rat MCA occlusion. APMIS: Acta Pathol., Microbiol. Immunol. Scand. 98 (1990), 851–857.
128. Kinouchi, R., Takeda, M., Yang, L., Wilhelmsson, U., Lundkvist, A., Pekny, M., Chen, D.F., Robust neural integration from retinal transplants in mice deficient in GFAP and vimentin. Nat. Neurosci. 6 (2003), 863–868.
129. Koehler, R.C., Roman, R.J., Harder, D.R., Astrocytes and the regulation of cerebral blood flow. Trends Neurosci. 32 (2009), 160–169.
130. Kraft, A.W., Hu, X., Yoon, H., Yan, P., Xiao, Q., Wang, Y., Gil, S.C., Brown, J., Wilhelmsson, U., Restivo, J.L., Cirrito, J.R., Holtzman, D.M., Kim, J., Pekny, M., Lee, J.M., Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice. FASEB J. 27 (2013), 187–198 (official publication of the Federation of American Societies for Experimental Biology).
131. Kuroiwa, T., Ting, P., Martinez, H., Klatzo, I., The biphasic opening of the blood–brain barrier to proteins following temporary middle cerebral artery occlusion. Acta Neuropathol. 68 (1985), 122–129.
132. Landis, D.M., The early reactions of non-neuronal cells to brain injury. Annu. Rev. Neurosci. 17 (1994), 133–151.
133. Larsson, A., Wilhelmsson, U., Pekna, M., Pekny, M., Increased cell proliferation and neurogenesis in the hippocampal dentate gyrus of old GFAP(−/−)Vim(−/−) mice. Neurochem. Res. 29 (2004), 2069–2073.
134. Lee, E.S., Sidoryk, M., Jiang, H., Yin, Z., Aschner, M., Estrogen and tamoxifen reverse manganese-induced glutamate transporter impairment in astrocytes. J. Neurochem. 110 (2009), 530–544.
135. Lee, H.Y., Hwang, I.Y., Im, H., Koh, J.Y., Kim, Y.H., Non-proteolytic neurotrophic effects of tissue plasminogen activator on cultured mouse cerebrocortical neurons. J. Neurochem. 101 (2007), 1236–1247.
136. Lee, T.H., Kato, H., Chen, S.T., Kogure, K., Itoyama, Y., Expression of nerve growth factor and trkA after transient focal cerebral ischemia in rats. Stroke 29 (1998), 1687–1696 (discussion 1697, a journal of cerebral circulation).
137. Lepekhin, E.A., Eliasson, C., Berthold, C.H., Berezin, V., Bock, E., Pekny, M., Intermediate filaments regulate astrocyte motility. J. Neurochem. 79 (2001), 617–625.
138. Li, C.Y., Li, X., Liu, S.F., Qu, W.S., Wang, W., Tian, D.S., Inhibition of mTOR pathway restrains astrocyte proliferation, migration and production of inflammatory mediators after oxygen-glucose deprivation and reoxygenation. Neurochem. Int. 83-84 (2015), 9–18.
139. Li, L., Lundkvist, A., Andersson, D., Wilhelmsson, U., Nagai, N., Pardo, A.C., Nodin, C., Stahlberg, A., Aprico, K., Larsson, K., Yabe, T., Moons, L., Fotheringham, A., Davies, I., Carmeliet, P., Schwartz, J.P., Pekna, M., Kubista, M., Blomstrand, F., Maragakis, N., Nilsson, M., Pekny, M., Protective role of reactive astrocytes in brain ischemia. J. Cereb. Blood Flow Metab. 28 (2008), 468–481.
140. Li, P.C., Jiao, Y., Ding, J., Chen, Y.C., Cui, Y., Qian, C., Yang, X.Y., Ju, S.H., Yao, H.H., Teng, G.J., Cystamine improves functional recovery via axon remodeling and neuroprotection after stroke in mice. CNS Neurosci. Therap. 21 (2015), 231–240.
141. Li, Y., Chen, J., Zhang, C.L., Wang, L., Lu, D., Katakowski, M., Gao, Q., Shen, L.H., Zhang, J., Lu, M., Chopp, M., Gliosis and brain remodeling after treatment of stroke in rats with marrow stromal cells. Glia 49 (2005), 407–417.
142. Li, Y., Chopp, M., Temporal profile of nestin expression after focal cerebral ischemia in adult rat. Brain Res. 838 (1999), 1–10.
143. Li, Y., Chopp, M., Marrow stromal cell transplantation in stroke and traumatic brain injury. Neurosci. Lett. 456 (2009), 120–123.
144. Li, Y., Chopp, M., Jiang, N., Yao, F., Zaloga, C., Temporal profile of in situ DNA fragmentation after transient middle cerebral artery occlusion in the rat. J. Cereb. Blood Flow Metab. 15 (1995), 389–397.
145. Li, Y., Chopp, M., Jiang, N., Zaloga, C., In situ detection of DNA fragmentation after focal cerebral ischemia in mice. Brain Res. Mol. Brain Res. 28 (1995), 164–168.
146. Li, Y., Chopp, M., Jiang, N., Zhang, Z.G., Zaloga, C., Induction of DNA fragmentation after 10 to 120 min of focal cerebral ischemia in rats. Stroke 26 (1995), 1252–1257 (discussion 1257–1258, a journal of cerebral circulation).
147. Li, Y., Chopp, M., Zhang, Z.G., Zhang, R.L., Expression of glial fibrillary acidic protein in areas of focal cerebral ischemia accompanies neuronal expression of 72-kDa heat shock protein. J. Neurol. Sci. 128 (1995), 134–142.
148. Li, Y., Liu, Z., Xin, H., Chopp, M., The role of astrocytes in mediating exogenous cell-based restorative therapy for stroke. Glia 62 (2014), 1–16.
149. Li, Y., McIntosh, K., Chen, J., Zhang, C., Gao, Q., Borneman, J., Raginski, K., Mitchell, J., Shen, L., Zhang, J., Lu, D., Chopp, M., Allogeneic bone marrow stromal cells promote glial-axonal remodeling without immunologic sensitization after stroke in rats. Exp. Neurol. 198 (2006), 313–325.
150. Li, Y., Sharov, V.G., Jiang, N., Zaloga, C., Sabbah, H.N., Chopp, M., Ultrastructural and light microscopic evidence of apoptosis after middle cerebral artery occlusion in the rat. Am. J. Pathol. 146 (1995), 1045–1051.
151. Liauw, J., Hoang, S., Choi, M., Eroglu, C., Choi, M., Sun, G.H., Percy, M., Wildman-Tobriner, B., Bliss, T., Guzman, R.G., Barres, B.A., Steinberg, G.K., Thrombospondins 1 and 2 are necessary for synaptic plasticity and functional recovery after stroke. J. Cereb. Blood Flow Metab. 28 (2008), 1722–1732.
152. Lin, J.H., Weigel, H., Cotrina, M.L., Liu, S., Bueno, E., Hansen, A.J., Hansen, T.W., Goldman, S., Nedergaard, M., Gap-junction-mediated propagation and amplification of cell injury. Nat. Neurosci. 1 (1998), 494–500.
153. Lin, R., Cai, J., Nathan, C., Wei, X., Schleidt, S., Rosenwasser, R., Iacovitti, L., Neurogenesis is enhanced by stroke in multiple new stem cell niches along the ventricular system at sites of high BBB permeability. Neurobiol. Dis. 74 (2015), 229–239.
154. Lin, T.N., Kim, G.M., Chen, J.J., Cheung, W.M., He, Y.Y., Hsu, C.Y., Differential regulation of thrombospondin-1 and thrombospondin-2 after focal cerebral ischemia/reperfusion. Stroke 34 (2003), 177–186 (a journal of cerebral circulation).
155. Lindholm, D., Castren, E., Hengerer, B., Zafra, F., Berninger, B., Thoenen, H., Differential regulation of nerve growth factor (NGF) synthesis in neurons and astrocytes by glucocorticoid hormones. Eur. J. Neurosci. 4 (1992), 404–410.
156. Lipton, P., Ischemic cell death in brain neurons. Physiol. Rev. 79 (1999), 1431–1568.
157. Liu, X., Sun, L., Torii, M., Rakic, P., Connexin 43 controls the multipolar phase of neuronal migration to the cerebral cortex. Proc. Natl. Acad. Sci. U.S.A. 109 (2012), 8280–8285.
158. Liu, Z., Li, Y., Cui, Y., Roberts, C., Lu, M., Wilhelmsson, U., Pekny, M., Chopp, M., Beneficial effects of gfap/vimentin reactive astrocytes for axonal remodeling and motor behavioral recovery in mice after stroke. Glia 62 (2014), 2022–2033.
159. Liu, Z., Li, Y., Qu, R., Shen, L., Gao, Q., Zhang, X., Lu, M., Savant-Bhonsale, S., Borneman, J., Chopp, M., Axonal sprouting into the denervated spinal cord and synaptic and postsynaptic protein expression in the spinal cord after transplantation of bone marrow stromal cell in stroke rats. Brain Res. 1149 (2007), 172–180.
160. Liu, Z., Li, Y., Zhang, Z.G., Cui, X., Cui, Y., Lu, M., Savant-Bhonsale, S., Chopp, M., Bone marrow stromal cells enhance inter- and intracortical axonal connections after ischemic stroke in adult rats. J. Cereb. Blood Flow Metab. 30 (2010), 1288–1295.
161. Lo, E.H., A new penumbra: transitioning from injury into repair after stroke. Nat. Med. 14 (2008), 497–500.
162. Love, S., Oxidative stress in brain ischemia. Brain Pathol. 9 (1999), 119–131.
163. Lu, B., Yokoyama, M., Dreyfus, C.F., Black, I.B., NGF gene expression in actively growing brain glia. J. Neurosci. 11 (1991), 318–326.
164. Lu, Y.B., Iandiev, I., Hollborn, M., Korber, N., Ulbricht, E., Hirrlinger, P.G., Pannicke, T., Wei, E.Q., Bringmann, A., Wolburg, H., Wilhelmsson, U., Pekny, M., Wiedemann, P., Reichenbach, A., Kas, J.A., Reactive glial cells: increased stiffness correlates with increased intermediate filament expression. FASEB J. 25 (2011), 624–631 (official publication of the Federation of American Societies for Experimental Biology).
165. Luo, C., Yi, B., Fan, W., Chen, K., Gui, L., Chen, Z., Li, L., Feng, H., Chi, L., Enhanced angiogenesis and astrocyte activation by ecdysterone treatment in a focal cerebral ischemia rat model. Acta Neurochir. 110:Supplement (2011), 151–155.
166. Magnusson, J.P., Goritz, C., Tatarishvili, J., Dias, D.O., Smith, E.M., Lindvall, O., Kokaia, Z., Frisen, J., A latent neurogenic program in astrocytes regulated by Notch signaling in the mouse. Science 346 (2014), 237–241.
167. Manley, G.T., Fujimura, M., Ma, T., Noshita, N., Filiz, F., Bollen, A.W., Chan, P., Verkman, A.S., Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke. Nat. Med. 6 (2000), 159–163.
168. Markiewicz, I., Lukomska, B., The role of astrocytes in the physiology and pathology of the central nervous system. Acta Neurobiol. Exp. 66 (2006), 343–358.
169. Martinez, A.D., Saez, J.C., Regulation of astrocyte gap junctions by hypoxia-reoxygenation. Brain Res. Brain Res. Rev. 32 (2000), 250–258.
170. Mathiisen, T.M., Lehre, K.P., Danbolt, N.C., Ottersen, O.P., The perivascular astroglial sheath provides a complete covering of the brain microvessels: an electron microscopic 3D reconstruction. Glia 58 (2010), 1094–1103.
171. Matsui, T., Mori, T., Tateishi, N., Kagamiishi, Y., Satoh, S., Katsube, N., Morikawa, E., Morimoto, T., Ikuta, F., Asano, T., Astrocytic activation and delayed infarct expansion after permanent focal ischemia in rats. Part I: Enhanced astrocytic synthesis of s-100beta in the periinfarct area precedes delayed infarct expansion. J. Cereb. Blood Flow Metab. 22 (2002), 711–722.
172. Mattson, M.P., NF-kappaB in the survival and plasticity of neurons. Neurochem. Res. 30 (2005), 883–893.
173. Mattson, M.P., Murrain, M., Guthrie, P.B., Kater, S.B., Fibroblast growth factor and glutamate: opposing roles in the generation and degeneration of hippocampal neuroarchitecture. J. Neurosci. 9 (1989), 3728–3740.
174. Mauch, D.H., Nagler, K., Schumacher, S., Goritz, C., Muller, E.C., Otto, A., Pfrieger, F.W., CNS synaptogenesis promoted by glia-derived cholesterol. Science 294 (2001), 1354–1357.
175. McKeon, R.J., Schreiber, R.C., Rudge, J.S., Silver, J., Reduction of neurite outgrowth in a model of glial scarring following CNS injury is correlated with the expression of inhibitory molecules on reactive astrocytes. J. Neurosci. 11 (1991), 3398–3411.
176. Mehta, S.H., Dhandapani, K.M., De Sevilla, L.M., Webb, R.C., Mahesh, V.B., Brann, D.W., Tamoxifen, a selective estrogen receptor modulator, reduces ischemic damage caused by middle cerebral artery occlusion in the ovariectomized female rat. Neuroendocrinology 77 (2003), 44–50.
177. Menet, V., Prieto, M., Privat, A., Gimenez, Ribotta, M., 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. U.S.A. 100 (2003), 8999–9004.
178. Miao, Y., Qiu, Y., Lin, Y., Miao, Z., Zhang, J., Lu, X., Protection by pyruvate against glutamate neurotoxicity is mediated by astrocytes through a glutathione-dependent mechanism. Mol. Biol. Rep. 38 (2011), 3235–3242.
179. Minnerup, J., Sutherland, B.A., Buchan, A.M., Kleinschnitz, C., Neuroprotection for stroke: current status and future perspectives. Int. J. Mol. Sci. 13 (2012), 11753–11772.
180. Mizui, T., Kinouchi, H., Chan, P.H., Depletion of brain glutathione by buthionine sulfoximine enhances cerebral ischemic injury in rats. Am. J. Physiol. 262 (1992), H313–H317.
181. Moskowitz, M.A., Lo, E.H., Iadecola, C., The science of stroke: mechanisms in search of treatments. Neuron 67 (2010), 181–198.
182. Mulligan, S.J., MacVicar, B.A., Calcium transients in astrocyte endfeet cause cerebrovascular constrictions. Nature 431 (2004), 195–199.
183. Mun-Bryce, S., Rosenberg, G.A., Matrix metalloproteinases in cerebrovascular disease. J. Cereb. Blood Flow Metab. 18 (1998), 1163–1172.
184. Nagy, J.I., Rash, J.E., Connexins and gap junctions of astrocytes and oligodendrocytes in the CNS. Brain Res. Brain Res. Rev. 32 (2000), 29–44.
185. Nakase, T., Fushiki, S., Naus, C.C., Astrocytic gap junctions composed of connexin 43 reduce apoptotic neuronal damage in cerebral ischemia. Stroke 34 (2003), 1987–1993 (a journal of cerebral circulation).
186. Nakase, T., Naus, C.C., Gap junctions and neurological disorders of the central nervous system. Biochim. Biophys. Acta 1662 (2004), 149–158.
187. Nakase, T., Sohl, G., Theis, M., Willecke, K., Naus, C.C., Increased apoptosis and inflammation after focal brain ischemia in mice lacking connexin43 in astrocytes. Am. J. Pathol. 164 (2004), 2067–2075.
188. Nakazawa, T., Takeda, M., Lewis, G.P., Cho, K.S., Jiao, J., Wilhelmsson, U., Fisher, S.K., Pekny, M., Chen, D.F., Miller, J.W., Attenuated glial reactions and photoreceptor degeneration after retinal detachment in mice deficient in glial fibrillary acidic protein and vimentin. Investig. Ophthalmol. Visual Sci. 48 (2007), 2760–2768.
189. Nardai, S., Dobolyi, A., Pal, G., Skopal, J., Pinter, N., Lakatos, K., Merkely, B., Nagy, Z., Selegiline promotes NOTCH-JAGGED signaling in astrocytes of the peri-infarct region and improves the functional integrity of the neurovascular unit in a rat model of focal ischemia. Restor. Neurol. Neurosci. 33 (2015), 1–14.
190. Naus, C.C., Ozog, M.A., Bechberger, J.F., Nakase, T., A neuroprotective role for gap junctions. Cell Commun. Adhes. 8 (2001), 325–328.
191. Nawashiro, H., Brenner, M., Fukui, S., Shima, K., Hallenbeck, J.M., High susceptibility to cerebral ischemia in GFAP-null mice. J. Cereb. Blood Flow Metab. 20 (2000), 1040–1044.
192. Nayak, A.R., Kashyap, R.S., Kabra, D., Purohit, H.J., Taori, G.M., Daginawala, H.F., Time course of inflammatory cytokines in acute ischemic stroke patients and their relation to inter-alfa trypsin inhibitor heavy chain 4 and outcome. Ann. Indian Acad. Neurol. 15 (2012), 181–185.
193. Nedergaard, M., Ransom, B., Goldman, S.A., New roles for astrocytes: redefining the functional architecture of the brain. Trends Neurosci. 26 (2003), 523–530.
194. Newman, E.A., New roles for astrocytes: regulation of synaptic transmission. Trends Neurosci. 26 (2003), 536–542.
195. Nicole, O., Ali, C., Docagne, F., Plawinski, L., MacKenzie, E.T., Vivien, D., Buisson, A., Neuroprotection mediated by glial cell line-derived neurotrophic factor: involvement of a reduction of NMDA-induced calcium influx by the mitogen-activated protein kinase pathway. J. Neurosci. 21 (2001), 3024–3033.
196. 2+ transients in astrocytes. Neuroscience 54 (1993), 605–614.
197. Niu, W., Zang, T., Zou, Y., Fang, S., Smith, D.K., Bachoo, R., Zhang, C.L., In vivo reprogramming of astrocytes to neuroblasts in the adult brain. Nat. Cell Biol. 15 (2013), 1164–1175.
198. Odemis, V., Moepps, B., Gierschik, P., Engele, J., Interleukin-6 and cAMP induce stromal cell-derived factor-1 chemotaxis in astroglia by up-regulating CXCR4 cell surface expression. Implications for brain inflammation. J. Biol. Chem. 277 (2002), 39801–39808.
199. Ohab, J.J., Fleming, S., Blesch, A., Carmichael, S.T., A neurovascular niche for neurogenesis after stroke. J. Neurosci. 26 (2006), 13007–13016.
200. Orrenius, S., Zhivotovsky, B., Nicotera, P., Regulation of cell death: the calcium-apoptosis link. Nat. Rev. Mol. Cell Biol. 4 (2003), 552–565.
201. Orzylowska, O., Oderfeld-Nowak, B., Zaremba, M., Januszewski, S., Mossakowski, M., Prolonged and concomitant induction of astroglial immunoreactivity of interleukin-1beta and interleukin-6 in the rat hippocampus after transient global ischemia. Neurosci. Lett. 263 (1999), 72–76.
202. Ouyang, Y.B., Voloboueva, L.A., Xu, L.J., Giffard, R.G., Selective dysfunction of hippocampal CA1 astrocytes contributes to delayed neuronal damage after transient forebrain ischemia. J. Neurosci. 27 (2007), 4253–4260.
203. Overman, J.J., Clarkson, A.N., Wanner, I.B., Overman, W.T., Eckstein, I., Maguire, J.L., Dinov, I.D., Toga, A.W., Carmichael, S.T., A role for ephrin-A5 in axonal sprouting, recovery, and activity-dependent plasticity after stroke. Proc. Natl. Acad. Sci. U.S.A. 109 (2012), E2230–E2239.
204. Ozog, M.A., Siushansian, R., Naus, C.C., Blocked gap junctional coupling increases glutamate-induced neurotoxicity in neuron–astrocyte co-cultures. J. Neuropathol. Exp. Neurol. 61 (2002), 132–141.
205. Pallari, H.M., Eriksson, J.E., Intermediate filaments as signaling platforms. Sci. STKE: Signal Transduct. Knowl. Environ., 2006, 2006, pe53.
206. Parent, J.M., Vexler, Z.S., Gong, C., Derugin, N., Ferriero, D.M., Rat forebrain neurogenesis and striatal neuron replacement after focal stroke. Ann. Neurol. 52 (2002), 802–813.
207. Pascual, O., Casper, K.B., Kubera, C., Zhang, J., Revilla-Sanchez, R., Sul, J.Y., Takano, H., Moss, S.J., McCarthy, K., Haydon, P.G., Astrocytic purinergic signaling coordinates synaptic networks. Science 310 (2005), 113–116.
208. Pavlichenko, N., Sokolova, I., Vijde, S., Shvedova, E., Alexandrov, G., Krouglyakov, P., Fedotova, O., Gilerovich, E.G., Polyntsev, D.G., Otellin, V.A., Mesenchymal stem cells transplantation could be beneficial for treatment of experimental ischemic stroke in rats. Brain Res. 1233 (2008), 203–213.
209. Pearson-Fuhrhop, K.M., Cramer, S.C., Genetic influences on neural plasticity. PM R 2 (2010), S227–S240.
210. Pekny, M., Johansson, C.B., Eliasson, C., Stakeberg, J., Wallen, A., Perlmann, T., Lendahl, U., Betsholtz, C., Berthold, C.H., Frisen, J., Abnormal reaction to central nervous system injury in mice lacking glial fibrillary acidic protein and vimentin. J. Cell Biol. 145 (1999), 503–514.
211. Pekny, M., Lane, E.B., Intermediate filaments and stress. Exp. Cell Res. 313 (2007), 2244–2254.
212. Pekny, M., Wilhelmsson, U., Pekna, M., The dual role of astrocyte activation and reactive gliosis. Neurosci. Lett. 565 (2014), 30–38.
213. Perea, G., Navarrete, M., Araque, A., Tripartite synapses: astrocytes process and control synaptic information. Trends Neurosci. 32 (2009), 421–431.
214. Petito, C.K., Early and late mechanisms of increased vascular permeability following experimental cerebral infarction. J. Neuropathol. Exp. Neurol. 38 (1979), 222–234.
215. Petzold, G.C., Albeanu, D.F., Sato, T.F., Murthy, V.N., Coupling of neural activity to blood flow in olfactory glomeruli is mediated by astrocytic pathways. Neuron 58 (2008), 897–910.
216. Porter, J.T., McCarthy, K.D., Astrocytic neurotransmitter receptors in situ and in vivo. Prog. Neurobiol. 51 (1997), 439–455.
217. Potokar, M., Kreft, M., Li, L., Daniel Andersson, J., Pangrsic, T., Chowdhury, H.H., Pekny, M., Zorec, R., Cytoskeleton and vesicle mobility in astrocytes. Traffic 8 (2007), 12–20.
218. Potokar, M., Stenovec, M., Gabrijel, M., Li, L., Kreft, M., Grilc, S., Pekny, M., Zorec, R., Intermediate filaments attenuate stimulation-dependent mobility of endosomes/lysosomes in astrocytes. Glia 58 (2010), 1208–1219.
219. Privat, A., Gimenez-Ribotta, M., Ridet, J.-L., Morphology of astrocytes. Ransom, B.R., Kettenmann, H., (eds.) Neuroglia, 1995, Oxford University Press, New York, NY, 3–22.
220. Qu, W.S., Wang, Y.H., Wang, J.P., Tang, Y.X., Zhang, Q., Tian, D.S., Yu, Z.Y., Xie, M.J., Wang, W., Galectin-1 enhances astrocytic BDNF production and improves functional outcome in rats following ischemia. Neurochem. Res. 35 (2010), 1716–1724.
221. Rabchevsky, A.G., Weinitz, J.M., Coulpier, M., Fages, C., Tinel, M., Junier, M.P., A role for transforming growth factor alpha as an inducer of astrogliosis. J. Neurosci. 18 (1998), 10541–10552.
222. Rami, A., Volkmann, T., Winckler, J., Effective reduction of neuronal death by inhibiting gap junctional intercellular communication in a rodent model of global transient cerebral ischemia. Exp. Neurol. 170 (2001), 297–304.
223. Ransom, B.R., Ransom, C.B., Astrocytes: multitalented stars of the central nervous system. Methods Mol. Biol. 814 (2012), 3–7.
224. Rathinam, M.L., Watts, L.T., Narasimhan, M., Riar, A.K., Mahimainathan, L., Henderson, G.I., Astrocyte mediated protection of fetal cerebral cortical neurons from rotenone and paraquat. Environ. Toxicol. Pharmacol. 33 (2012), 353–360.
225. Rawanduzy, A., Hansen, A., Hansen, T.W., Nedergaard, M., Effective reduction of infarct volume by gap junction blockade in a rodent model of stroke. J. Neurosurg. 87 (1997), 916–920.
226. Reichenbach, A., Wolburg, H., Astrocytes and ependymal glia. Kettenmann, H., Ransom, B.R., (eds.) Neuroglia, 2013, Oxford University Press, New York, NY, 35–49.
227. Reitmeir, R., Kilic, E., Kilic, U., Bacigaluppi, M., ElAli, A., Salani, G., Pluchino, S., Gassmann, M., Hermann, D.M., Post-acute delivery of erythropoietin induces stroke recovery by promoting perilesional tissue remodelling and contralesional pyramidal tract plasticity. Brain 134 (2011), 84–99.
228. Ridet, J.L., Malhotra, S.K., Privat, A., Gage, F.H., Reactive astrocytes: cellular and molecular cues to biological function. Trends Neurosci. 20 (1997), 570–577.
229. Rosenberg, G.A., Estrada, E.Y., Dencoff, J.E., Matrix metalloproteinases and TIMPs are associated with blood–brain barrier opening after reperfusion in rat brain. Stroke 29 (1998), 2189–2195 (a journal of cerebral circulation).
230. Rosenberg, P.A., Aizenman, E., Hundred-fold increase in neuronal vulnerability to glutamate toxicity in astrocyte-poor cultures of rat cerebral cortex. Neurosci. Lett. 103 (1989), 162–168.
231. Rossi, D.J., Brady, J.D., Mohr, C., Astrocyte metabolism and signaling during brain ischemia. Nat. Neurosci. 10 (2007), 1377–1386.
232. Rother, J., Neuroprotection does not work!. Stroke 39 (2008), 523–524 (a journal of cerebral circulation).
233. Rouach, N., Avignone, E., Meme, W., Koulakoff, A., Venance, L., Blomstrand, F., Giaume, C., Gap junctions and connexin expression in the normal and pathological central nervous system. Biol. Cell 94 (2002), 457–475 (under the auspices of the European Cell Biology Organization).
234. Rouach, N., Glowinski, J., Giaume, C., Activity-dependent neuronal control of gap-junctional communication in astrocytes. J. Cell Biol. 149 (2000), 1513–1526.
235. Rouach, N., Koulakoff, A., Abudara, V., Willecke, K., Giaume, C., Astroglial metabolic networks sustain hippocampal synaptic transmission. Science 322 (2008), 1551–1555.
236. Saadoun, S., Papadopoulos, M.C., Watanabe, H., Yan, D., Manley, G.T., Verkman, A.S., Involvement of aquaporin-4 in astroglial cell migration and glial scar formation. J. Cell Sci. 118 (2005), 5691–5698.
237. Saito, R., Graf, R., Hubel, K., Fujita, T., Rosner, G., Heiss, W.D., Reduction of infarct volume by halothane: effect on cerebral blood flow or perifocal spreading depression-like depolarizations. J. Cereb. Blood Flow Metab. 17 (1997), 857–864.
238. Sancho-Tello, M., Valles, S., Montoliu, C., Renau-Piqueras, J., Guerri, C., Developmental pattern of GFAP and vimentin gene expression in rat brain and in radial glial cultures. Glia 15 (1995), 157–166.
239. Sasaki, T., Hirabayashi, J., Manya, H., Kasai, K., Endo, T., Galectin-1 induces astrocyte differentiation, which leads to production of brain-derived neurotrophic factor. Glycobiology 14 (2004), 357–363.
240. Sattler, R., Tymianski, M., Molecular mechanisms of glutamate receptor-mediated excitotoxic neuronal cell death. Mol. Neurobiol. 24 (2001), 107–129.
241. Scarisbrick, I.A., Radulovic, M., Burda, J.E., Larson, N., Blaber, S.I., Giannini, C., Blaber, M., Vandell, A.G., Kallikrein 6 is a novel molecular trigger of reactive astrogliosis. Biol. Chem. 393 (2012), 355–367.
242. Scemes, E., Suadicani, S.O., Spray, D.C., Intercellular communication in spinal cord astrocytes: fine tuning between gap junctions and P2 nucleotide receptors in calcium wave propagation. J. Neurosci. 20 (2000), 1435–1445.
243. Schaar, D.G., Sieber, B.A., Dreyfus, C.F., Black, I.B., Regional and cell-specific expression of GDNF in rat brain. Exp. Neurol. 124 (1993), 368–371.
244. Schummers, J., Yu, H., Sur, M., Tuned responses of astrocytes and their influence on hemodynamic signals in the visual cortex. Science 320 (2008), 1638–1643.
245. Semkova, I., Wolz, P., Schilling, M., Krieglstein, J., Selegiline enhances NGF synthesis and protects central nervous system neurons from excitotoxic and ischemic damage. Eur. J. Pharmacol. 315 (1996), 19–30.
246. Sharif, A., Legendre, P., Prevot, V., Allet, C., Romao, L., Studler, J.M., Chneiweiss, H., Junier, M.P., Transforming growth factor alpha promotes sequential conversion of mature astrocytes into neural progenitors and stem cells. Oncogene 26 (2007), 2695–2706.
247. Shen, L.H., Li, Y., Chen, J., Cui, Y., Zhang, C., Kapke, A., Lu, M., Savant-Bhonsale, S., Chopp, M., One-year follow-up after bone marrow stromal cell treatment in middle-aged female rats with stroke. Stroke 38 (2007), 2150–2156 (a journal of cerebral circulation).
248. Shen, L.H., Li, Y., Chopp, M., Astrocytic endogenous glial cell derived neurotrophic factor production is enhanced by bone marrow stromal cell transplantation in the ischemic boundary zone after stroke in adult rats. Glia 58 (2010), 1074–1081.
249. Shen, L.H., Li, Y., Gao, Q., Savant-Bhonsale, S., Chopp, M., Down-regulation of neurocan expression in reactive astrocytes promotes axonal regeneration and facilitates the neurorestorative effects of bone marrow stromal cells in the ischemic rat brain. Glia 56 (2008), 1747–1754.
250. Shen, Y., He, P., Fan, Y.Y., Zhang, J.X., Yan, H.J., Hu, W.W., Ohtsu, H., Chen, Z., Carnosine protects against permanent cerebral ischemia in histidine decarboxylase knockout mice by reducing glutamate excitotoxicity. Free Radic. Biol. Med. 48 (2010), 727–735.
251. Shigetomi, E., Bowser, D.N., Sofroniew, M.V., Khakh, B.S., Two forms of astrocyte calcium excitability have distinct effects on NMDA receptor-mediated slow inward currents in pyramidal neurons. J. Neurosci. 28 (2008), 6659–6663.
252. Silver, J., Miller, J.H., Regeneration beyond the glial scar. Nat. Rev. Neurosci. 5 (2004), 146–156.
253. Simard, M., Arcuino, G., Takano, T., Liu, Q.S., Nedergaard, M., Signaling at the gliovascular interface. J. Neurosci. 23 (2003), 9254–9262.
254. Sivenius, J., Sarasoja, T., Aaltonen, H., Heinonen, E., Kilkku, O., Reinikainen, K., Selegiline treatment facilitates recovery after stroke. Neurorehabil. Neural Repair 15 (2001), 183–190.
255. Smith, G.M., Strunz, C., Growth factor and cytokine regulation of chondroitin sulfate proteoglycans by astrocytes. Glia 52 (2005), 209–218.
256. Sofroniew, M.V., Reactive astrocytes in neural repair and protection. Neuroscientist 11 (2005), 400–407.
257. Sofroniew, M.V., Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci. 32 (2009), 638–647.
258. Song, H., Stevens, C.F., Gage, F.H., Astroglia induce neurogenesis from adult neural stem cells. Nature 417 (2002), 39–44.
259. Stecca, B., Ruiz i Altaba, A., Brain as a paradigm of organ growth: Hedgehog-Gli signaling in neural stem cells and brain tumors. J. Neurobiol. 64 (2005), 476–490.
260. Stellwagen, D., Malenka, R.C., Synaptic scaling mediated by glial TNF-alpha. Nature 440 (2006), 1054–1059.
261. Stoll, G., Jander, S., Schroeter, M., Inflammation and glial responses in ischemic brain lesions. Prog. Neurobiol. 56 (1998), 149–171.
262. Stroke Therapy Academic Industry Roundtable, Recommendations for clinical trial evaluation of acute stroke therapies. Stroke 32 (2001), 1598–1606 (a journal of cerebral circulation).
263. Sugawara, T., Chan, P.H., Reactive oxygen radicals and pathogenesis of neuronal death after cerebral ischemia. Antioxid. Redox Signal. 5 (2003), 597–607.
264. Sun, Y., Jin, K., Xie, L., Childs, J., Mao, X.O., Logvinova, A., Greenberg, D.A., VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia. J. Clin. Invest. 111 (2003), 1843–1851.
265. Sutherland, B.A., Minnerup, J., Balami, J.S., Arba, F., Buchan, A.M., Kleinschnitz, C., Neuroprotection for ischaemic stroke: translation from the bench to the bedside. Int. J. Stroke 7 (2012), 407–418.
266. Sutor, B., Hagerty, T., Involvement of gap junctions in the development of the neocortex. Biochim. Biophys. Acta 1719 (2005), 59–68.
267. Swanson, R.A., Ying, W., Kauppinen, T.M., Astrocyte influences on ischemic neuronal death. Curr. Mol. Med. 4 (2004), 193–205.
268. Sykova, E., Glial diffusion barriers during aging and pathological states. Prog. Brain Res. 132 (2001), 339–363.
269. Szydlowska, K., Zawadzka, M., Kaminska, B., Neuroprotectant FK506 inhibits glutamate-induced apoptosis of astrocytes in vitro and in vivo. J. Neurochem. 99 (2006), 965–975.
270. Teramoto, T., Qiu, J., Plumier, J.C., Moskowitz, M.A., EGF amplifies the replacement of parvalbumin-expressing striatal interneurons after ischemia. J. Clin. Invest. 111 (2003), 1125–1132.
271. Thiele, C., Hannah, M.J., Fahrenholz, F., Huttner, W.B., Cholesterol binds to synaptophysin and is required for biogenesis of synaptic vesicles. Nat. Cell Biol. 2 (2000), 42–49.
272. Thored, P., Arvidsson, A., Cacci, E., Ahlenius, H., Kallur, T., Darsalia, V., Ekdahl, C.T., Kokaia, Z., Lindvall, O., Persistent production of neurons from adult brain stem cells during recovery after stroke. Stem Cells 24 (2006), 739–747.
273. Thoren, A.E., Helps, S.C., Nilsson, M., Sims, N.R., Astrocytic function assessed from 1-14C-acetate metabolism after temporary focal cerebral ischemia in rats. J. Cereb. Blood Flow Metab. 25 (2005), 440–450.
274. Tian, W., Kyriakides, T.R., Matrix metalloproteinase-9 deficiency leads to prolonged foreign body response in the brain associated with increased IL-1beta levels and leakage of the blood–brain barrier. Matrix Biol. 28 (2009), 148–159 (journal of the International Society for Matrix Biology).
275. Tian, W., Sawyer, A., Kocaoglu, F.B., Kyriakides, T.R., Astrocyte-derived thrombospondin-2 is critical for the repair of the blood–brain barrier. Am. J. Pathol. 179 (2011), 860–868.
276. Tokumine, J., Kakinohana, O., Cizkova, D., Smith, D.W., Marsala, M., Changes in spinal GDNF, BDNF, and NT-3 expression after transient spinal cord ischemia in the rat. J. Neurosci. Res. 74 (2003), 552–561.
277. Tourdias, T., Mori, N., Dragonu, I., Cassagno, N., Boiziau, C., Aussudre, J., Brochet, B., Moonen, C., Petry, K.G., Dousset, V., Differential aquaporin 4 expression during edema build-up and resolution phases of brain inflammation. J. Neuroinflamm., 8, 2011, 143.
278. Tournell, C.E., Bergstrom, R.A., Ferreira, A., Progesterone-induced agrin expression in astrocytes modulates glia-neuron interactions leading to synapse formation. Neuroscience 141 (2006), 1327–1338.
279. Treutiger, C.J., Mullins, G.E., Johansson, A.S., Rouhiainen, A., Rauvala, H.M., Erlandsson-Harris, H., Andersson, U., Yang, H., Tracey, K.J., Andersson, J., Palmblad, J.E., High mobility group 1 B-box mediates activation of human endothelium. J. Intern. Med. 254 (2003), 375–385.
280. Tuinstra, H.M., Ducommun, M.M., Briley, W.E., Shea, L.D., Gene delivery to overcome astrocyte inhibition of axonal growth: an in vitro model of the glial scar. Biotechnol. Bioeng. 110 (2013), 947–957.
281. Turner, R.C., Dodson, S.C., Rosen, C.L., Huber, J.D., The science of cerebral ischemia and the quest for neuroprotection: navigating past failure to future success. J. Neurosurg. 118 (2013), 1072–1085.
282. Tuttolomondo, A., Di Raimondo, D., di Sciacca, R., Pinto, A., Licata, G., Inflammatory cytokines in acute ischemic stroke. Curr. Pharm. Des. 14 (2008), 3574–3589.
283. Valles, S., Sancho-Tello, M., Minana, R., Climent, E., Renau-Piqueras, J., Guerri, C., Glial fibrillary acidic protein expression in rat brain and in radial glia culture is delayed by prenatal ethanol exposure. J. Neurochem. 67 (1996), 2425–2433.
284. Vardjan, N., Gabrijel, M., Potokar, M., Svajger, U., Kreft, M., Jeras, M., de Pablo, Y., Faiz, M., Pekny, M., Zorec, R., IFN-gamma-induced increase in the mobility of MHC class II compartments in astrocytes depends on intermediate filaments. J. Neuroinflamm., 9, 2012, 144.
285. Venters, H.D., Dantzer, R., Kelley, K.W., Tumor necrosis factor-alpha induces neuronal death by silencing survival signals generated by the type I insulin-like growth factor receptor. Ann. N. Y. Acad. Sci. 917 (2000), 210–220.
286. Verkhratsky, A., Physiology of neuronal-glial networking. Neurochem. Int. 57 (2010), 332–343.
287. Verkhratsky, A., Kettenmann, H., Calcium signalling in glial cells. Trends Neurosci. 19 (1996), 346–352.
288. Verkhratsky, A., Kirchhoff, F., Glutamate-mediated neuronal-glial transmission. J. Anat. 210 (2007), 651–660.
289. Wang, F.W., Hao, H.B., Zhao, S.D., Zhang, Y.M., Liu, Q., Liu, H.J., Liu, S.M., Yuan, Q.H., Bing, L.J., Ling, E.A., Hao, A.J., Roles of activated astrocyte in neural stem cell proliferation and differentiation. Stem Cell Res. 7 (2011), 41–53.
290. Wang, H.Y., Wang, G.L., Yu, Y.H., Wang, Y., The role of phosphoinositide-3-kinase/Akt pathway in propofol-induced postconditioning against focal cerebral ischemia-reperfusion injury in rats. Brain Res. 1297 (2009), 177–184.
291. Wang, J., Shi, Y., Zhang, L., Zhang, F., Hu, X., Zhang, W., Leak, R.K., Gao, Y., Chen, L., Chen, J., Omega-3 polyunsaturated fatty acids enhance cerebral angiogenesis and provide long-term protection after stroke. Neurobiol. Dis. 68 (2014), 91–103.
292. Wang, L., Zhang, Z., Wang, Y., Zhang, R., Chopp, M., Treatment of stroke with erythropoietin enhances neurogenesis and angiogenesis and improves neurological function in rats. Stroke 35 (2004), 1732–1737 (a journal of cerebral circulation).
293. Wang, W., Redecker, C., Yu, Z.Y., Xie, M.J., Tian, D.S., Zhang, L., Bu, B.T., Witte, O.W., Rat focal cerebral ischemia induced astrocyte proliferation and delayed neuronal death are attenuated by cyclin-dependent kinase inhibition. J. Clin. Neurosci. 15 (2008), 278–285.
294. Wang, Y., Jin, S., Sonobe, Y., Cheng, Y., Horiuchi, H., Parajuli, B., Kawanokuchi, J., Mizuno, T., Takeuchi, H., Suzumura, A., Interleukin-1beta induces blood–brain barrier disruption by downregulating Sonic hedgehog in astrocytes. PLoS ONE, 9, 2014, e110024.
295. Wang, Y., Lin, S.Z., Chiou, A.L., Williams, L.R., Hoffer, B.J., Glial cell line-derived neurotrophic factor protects against ischemia-induced injury in the cerebral cortex. J. Neurosci. 17 (1997), 4341–4348.
296. Wei, L., Cui, L., Snider, B.J., Rivkin, M., Yu, S.S., Lee, C.S., Adams, L.D., Gottlieb, D.I., Johnson, E.M. Jr., Yu, S.P., Choi, D.W., Transplantation of embryonic stem cells overexpressing Bcl-2 promotes functional recovery after transient cerebral ischemia. Neurobiol. Dis. 19 (2005), 183–193.
297. Weller, M.L., Stone, I.M., Goss, A., Rau, T., Rova, C., Poulsen, D.J., Selective overexpression of excitatory amino acid transporter 2 (EAAT2) in astrocytes enhances neuroprotection from moderate but not severe hypoxia-ischemia. Neuroscience 155 (2008), 1204–1211.
298. Wick, A., Wick, W., Waltenberger, J., Weller, M., Dichgans, J., Schulz, J.B., Neuroprotection by hypoxic preconditioning requires sequential activation of vascular endothelial growth factor receptor and Akt. J. Neurosci. 22 (2002), 6401–6407.
299. −/− mice. Stem cells 25 (2007), 2619–2627.
300. Wilhelmsson, U., Bushong, E.A., Price, D.L., Smarr, B.L., Phung, V., Terada, M., Ellisman, M.H., Pekny, M., Redefining the concept of reactive astrocytes as cells that remain within their unique domains upon reaction to injury. Proc. Natl. Acad. Sci. U.S.A. 103 (2006), 17513–17518.
301. Wilhelmsson, U., Faiz, M., de Pablo, Y., Sjoqvist, M., Andersson, D., Widestrand, A., Potokar, M., Stenovec, M., Smith, P.L., Shinjyo, N., Pekny, T., Zorec, R., Stahlberg, A., Pekna, M., Sahlgren, C., Pekny, M., Astrocytes negatively regulate neurogenesis through the Jagged1-mediated Notch pathway. Stem Cells 30 (2012), 2320–2329.
302. Wilhelmsson, U., Li, L., Pekna, M., Berthold, C.H., Blom, S., Eliasson, C., Renner, O., Bushong, E., Ellisman, M., Morgan, T.E., Pekny, M., Absence of glial fibrillary acidic protein and vimentin prevents hypertrophy of astrocytic processes and improves post-traumatic regeneration. J. Neurosci. 24 (2004), 5016–5021.
303. Winter, C.G., Saotome, Y., Levison, S.W., Hirsh, D., A role for ciliary neurotrophic factor as an inducer of reactive gliosis, the glial response to central nervous system injury. Proc. Natl. Acad. Sci. U.S.A. 92 (1995), 5865–5869.
304. 2+ release enhances neuroprotection by increasing astrocyte mitochondrial metabolism during aging. J. Neurosci. 27 (2007), 6510–6520.
305. Wu, X., Zhou, C., Du, F., Lu, Y., Peng, B., Chen, L., Zhu, L., Ginkgolide B preconditioning on astrocytes promotes neuronal survival in ischemic injury via up-regulating erythropoietin secretion. Neurochem. Int. 62 (2013), 157–164.
306. Wullner, U., Seyfried, J., Groscurth, P., Beinroth, S., Winter, S., Gleichmann, M., Heneka, M., Loschmann, P., Schulz, J.B., Weller, M., Klockgether, T., Glutathione depletion and neuronal cell death: the role of reactive oxygen intermediates and mitochondrial function. Brain Res. 826 (1999), 53–62.
307. Xia, C.F., Yin, H., Borlongan, C.V., Chao, J., Chao, L., Adrenomedullin gene delivery protects against cerebral ischemic injury by promoting astrocyte migration and survival. Hum. Gene Ther. 15 (2004), 1243–1254.
308. Xin, H., Li, Y., Chen, X., Chopp, M., Bone marrow stromal cells induce BMP2/4 production in oxygen-glucose-deprived astrocytes, which promotes an astrocytic phenotype in adult subventricular progenitor cells. J. Neurosci. Res. 83 (2006), 1485–1493.
309. Xin, H., Li, Y., Chopp, M., Exosomes/miRNAs as mediating cell-based therapy of stroke. Front. Cell. Neurosci., 8, 2014, 377.
310. Xin, H., Li, Y., Shen, L.H., Liu, X., Hozeska-Solgot, A., Zhang, R.L., Zhang, Z.G., Chopp, M., Multipotent mesenchymal stromal cells increase tPA expression and concomitantly decrease PAI-1 expression in astrocytes through the sonic hedgehog signaling pathway after stroke (in vitro study). J. Cereb. Blood Flow Metab. 31 (2011), 2181–2188.
311. Xin, H., Li, Y., Shen, L.H., Liu, X., Wang, X., Zhang, J., Pourabdollah-Nejad, D.S., Zhang, C., Zhang, L., Jiang, H., Zhang, Z.G., Chopp, M., Increasing tPA activity in astrocytes induced by multipotent mesenchymal stromal cells facilitate neurite outgrowth after stroke in the mouse. PLoS ONE, 5, 2010, e9027.
312. Xu, L., Emery, J.F., Ouyang, Y.B., Voloboueva, L.A., Giffard, R.G., Astrocyte targeted overexpression of Hsp72 or SOD2 reduces neuronal vulnerability to forebrain ischemia. Glia 58 (2010), 1042–1049.
313. Yamagata, K., Tagami, M., Ikeda, K., Tsumagari, S., Yamori, Y., Nara, Y., Differential regulation of glial cell line-derived neurotrophic factor (GDNF) mRNA expression during hypoxia and reoxygenation in astrocytes isolated from stroke-prone spontaneously hypertensive rats. Glia 37 (2002), 1–7.
314. Yamakuni, T., Ozawa, F., Hishinuma, F., Kuwano, R., Takahashi, Y., Amano, T., Expression of beta-nerve growth factor mRNA in rat glioma cells and astrocytes from rat brain. FEBS Lett. 223 (1987), 117–121.
315. Yang, G.Y., Gong, C., Qin, Z., Liu, X.H., Lorris Betz, A., Tumor necrosis factor alpha expression produces increased blood–brain barrier permeability following temporary focal cerebral ischemia in mice. Brain Res. Mol. Brain Res. 69 (1999), 135–143.
316. Yasuda, Y., Tateishi, N., Shimoda, T., Satoh, S., Ogitani, E., Fujita, S., Relationship between S100beta and GFAP expression in astrocytes during infarction and glial scar formation after mild transient ischemia. Brain Res. 1021 (2004), 20–31.
317. Zacharek, A., Chen, J., Cui, X., Li, A., Li, Y., Roberts, C., Feng, Y., Gao, Q., Chopp, M., Angiopoietin1/Tie2 and VEGF/Flk1 induced by MSC treatment amplifies angiogenesis and vascular stabilization after stroke. J. Cereb. Blood Flow Metab. 27 (2007), 1684–1691.
318. Zamanian, J.L., Xu, L., Foo, L.C., Nouri, N., Zhou, L., Giffard, R.G., Barres, B.A., Genomic analysis of reactive astrogliosis. J. Neurosci. 32 (2012), 6391–6410.
319. Zhang, J., Yu, Z., Yu, Z., Yang, Z., Zhao, H., Liu, L., Zhao, J., rAAV-mediated delivery of brain-derived neurotrophic factor promotes neurite outgrowth and protects neurodegeneration in focal ischemic model. Int. J. Clin. Exp. Pathol. 4 (2011), 496–504.
320. Zhang, R., Zhang, L., Zhang, Z., Wang, Y., Lu, M., Lapointe, M., Chopp, M., A nitric oxide donor induces neurogenesis and reduces functional deficits after stroke in rats. Ann. Neurol. 50 (2001), 602–611.
321. Zhang, R., Zhang, Z., Wang, L., Wang, Y., Gousev, A., Zhang, L., Ho, K.L., Morshead, C., Chopp, M., Activated neural stem cells contribute to stroke-induced neurogenesis and neuroblast migration toward the infarct boundary in adult rats. J. Cereb. Blood Flow Metab. 24 (2004), 441–448.
322. Zhang, R.L., LeTourneau, Y., Gregg, S.R., Wang, Y., Toh, Y., Robin, A.M., Zhang, Z.G., Chopp, M., Neuroblast division during migration toward the ischemic striatum: a study of dynamic migratory and proliferative characteristics of neuroblasts from the subventricular zone. J. Neurosci. 27 (2007), 3157–3162.
323. Zhang, R.L., Zhang, Z.G., Wang, Y., LeTourneau, Y., Liu, X.S., Zhang, X., Gregg, S.R., Wang, L., Chopp, M., Stroke induces ependymal cell transformation into radial glia in the subventricular zone of the adult rodent brain. J. Cereb. Blood Flow Metab. 27 (2007), 1201–1212.
324. Zhang, Y., Jin, Y., Behr, M.J., Feustel, P.J., Morrison, J.P., Kimelberg, H.K., Behavioral and histological neuroprotection by tamoxifen after reversible focal cerebral ischemia. Exp. Neurol. 196 (2005), 41–46.
325. Zhang, Z.G., Chopp, M., Neurorestorative therapies for stroke: underlying mechanisms and translation to the clinic. Lancet Neurol. 8 (2009), 491–500.
326. Zhang, Z.G., Zhang, L., Jiang, Q., Zhang, R., Davies, K., Powers, C., Bruggen, N., Chopp, M., VEGF enhances angiogenesis and promotes blood–brain barrier leakage in the ischemic brain. J. Clin. Invest. 106 (2000), 829–838.
327. Zhao, B.Q., Wang, S., Kim, H.Y., Storrie, H., Rosen, B.R., Mooney, D.J., Wang, X., Lo, E.H., Role of matrix metalloproteinases in delayed cortical responses after stroke. Nat. Med. 12 (2006), 441–445.
328. Zheng, W., Talley Watts, L., Holstein, D.M., Wewer, J., Lechleiter, J.D., P2Y1R-initiated, IP3R-dependent stimulation of astrocyte mitochondrial metabolism reduces and partially reverses ischemic neuronal damage in mouse. J. Cereb. Blood Flow Metab. 33 (2013), 600–611.
329. Zheng, W., Watts, L.T., Holstein, D.M., Prajapati, S.I., Keller, C., Grass, E.H., Walter, C.A., Lechleiter, J.D., Purinergic receptor stimulation reduces cytotoxic edema and brain infarcts in mouse induced by photothrombosis by energizing glial mitochondria. PLoS ONE, 5, 2010, e14401.
330. Zhou, Y., Fang, S.H., Ye, Y.L., Chu, L.S., Zhang, W.P., Wang, M.L., Wei, E.Q., Caffeic acid ameliorates early and delayed brain injuries after focal cerebral ischemia in rats. Acta Pharmacol. Sin. 27 (2006), 1103–1110.
331. Zonta, M., Angulo, M.C., Gobbo, S., Rosengarten, B., Hossmann, K.A., Pozzan, T., Carmignoto, G., Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation. Nat. Neurosci. 6 (2003), 43–50.
332. Zorowitz, R.D., Chen, E., Tong, K.B., Laouri, M., Costs and rehabilitation use of stroke survivors: a retrospective study of medicare beneficiaries. Top. Stroke Rehabil. 16 (2009), 309–320.
333. Zuo, J., Ferguson, T.A., Hernandez, Y.J., Stetler-Stevenson, W.G., Muir, D., Neuronal matrix metalloproteinase-2 degrades and inactivates a neurite-inhibiting chondroitin sulfate proteoglycan. J. Neurosci. 18 (1998), 5203–5211.