Astrocytic response to cerebral ischemia is influenced by sex differences and impaired by aging

Neurobiology of Disease

Volumn 85, Issue , 2016, Pages 245-253

  Chisholm, Nioka C ^a   Sohrabji, Farida ^a  

^a TEXAS A M COLLEGE OF MEDICINE   (United States)

Author keywords

Astrocyte; Blood brain barrier; Epigenetics; Estrogen; Excitotoxicity; GFAP; Glutamate; H3K4me3; HDAC; Hormones; IGF 1; Methylation; MicroRNA; Neuroinflammation; Oxidative stress; Progesterone; Sex differences; Stroke; VEGF

Indexed keywords

ESTROGEN; GLUTAMIC ACID; HISTONE ACETYLTRANSFERASE; HISTONE DEACETYLASE; MICRORNA; NEUROTROPHIC FACTOR; PROGESTERONE; SEX HORMONE; SOMATOMEDIN C; VASCULOTROPIN;

AGING; ASTROCYTE; BLOOD BRAIN BARRIER; BRAIN ISCHEMIA; CELL DEATH; CELL PROLIFERATION; DNA MODIFICATION; EPIGENETICS; EXCITOTOXICITY; GENE EXPRESSION; GENETIC ANALYSIS; GLIOSIS; METHYLATION; NERVOUS SYSTEM INFLAMMATION; NEUROPROTECTION; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SEX DIFFERENCE; ANIMAL; BRAIN; HUMAN; PATHOPHYSIOLOGY; PHYSIOLOGY; SEXUAL DEVELOPMENT;

AGING; ANIMALS; ASTROCYTES; BRAIN; BRAIN ISCHEMIA; HUMANS; SEX CHARACTERISTICS;

EID: 84949725932     PISSN: 09699961     EISSN: 1095953X     Source Type: Journal    
DOI: 10.1016/j.nbd.2015.03.028     Document Type: Review

References (150)

1. Abbott N.J., Ronnback L., Hansson E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat. Rev. Neurosci. 2006, 7:41-53.
2. Alkayed N.J., Harukuni I., Kimes A.S., London E.D., Traystman R.J., Hurn P.D. Gender-linked brain injury in experimental stroke. Stroke 1998, 29:159-165. (discussion 166).
3. Anderson C.M., Swanson R.A. Astrocyte glutamate transport: review of properties, regulation, and physiological functions. Glia 2000, 32:1-14.
4. Appelros P., Stegmayr B., Terent A. Sex differences in stroke epidemiology: a systematic review. Stroke 2009, 40:1082-1090.
5. Araque A., Navarrete M. Glial cells in neuronal network function. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2010, 365:2375-2381.
6. Arevalo M.A., Santos-Galindo M., Acaz-Fonseca E., Azcoitia I., Garcia-Segura L.M. Gonadal hormones and the control of reactive gliosis. Horm. Behav. 2013, 63:216-221.
7. Arias C., Zepeda A., Hernandez-Ortega K., Leal-Galicia P., Lojero C., Camacho-Arroyo I. Sex and estrous cycle-dependent differences in glial fibrillary acidic protein immunoreactivity in the adult rat hippocampus. Horm. Behav. 2009, 55:257-263.
8. Arimoto J.M., Wong A., Rozovsky I., Lin S.W., Morgan T.E., Finch C.E. Age increase of estrogen receptor-alpha (ERalpha) in cortical astrocytes impairs neurotrophic support in male and female rats. Endocrinology 2013, 154:2101-2113.
9. Arnold S., de Araujo G.W., Beyer C. Gender-specific regulation of mitochondrial fusion and fission gene transcription and viability of cortical astrocytes by steroid hormones. J. Mol. Endocrinol. 2008, 41:289-300.
10. Azcoitia I., Sierra A., Garcia-Segura L.M. Localization of estrogen receptor beta-immunoreactivity in astrocytes of the adult rat brain. Glia 1999, 26:260-267.
11. Azcoitia I., Sierra A., Veiga S., Garcia-Segura L.M. Aromatase expression by reactive astroglia is neuroprotective. Ann. N. Y. Acad. Sci. 2003, 1007:298-305.
12. Azcoitia I., Santos-Galindo M., Arevalo M.A., Garcia-Segura L.M. Role of astroglia in the neuroplastic and neuroprotective actions of estradiol. Eur. J. Neurosci. 2010, 32:1995-2002.
13. Badan I., Buchhold B., Hamm A., Gratz M., Walker L.C., Platt D., Kessler C., Popa-Wagner A. Accelerated glial reactivity to stroke in aged rats correlates with reduced functional recovery. J. Cereb. Blood Flow Metab. 2003, 23:845-854.
14. Baltan S. Histone deacetylase inhibitors preserve function in aging axons. J. Neurochem. 2012, 123(Suppl. 2):108-115.
15. Banks W.A., Moinuddin A., Morley J.E. Regional transport of TNF-alpha across the blood-brain barrier in young ICR and young and aged SAMP8 mice. Neurobiol. Aging 2001, 22:671-676.
16. Bellaver B., Souza D.G., Souza D.O., Quincozes-Santos A. Resveratrol increases antioxidant defenses and decreases proinflammatory cytokines in hippocampal astrocyte cultures from newborn, adult and aged Wistar rats. Toxicol. In Vitro 2014, 28:479-484.
17. Berchtold N.C., Cribbs D.H., Coleman P.D., Rogers J., Head E., Kim R., Beach T., Miller C., Troncoso J., Trojanowski J.Q., Zielke H.R., Cotman C.W. Gene expression changes in the course of normal brain aging are sexually dimorphic. Proc. Natl. Acad. Sci. U. S. A. 2008, 105:15605-15610.
18. Bernal G.M., Peterson D.A. Phenotypic and gene expression modification with normal brain aging in GFAP-positive astrocytes and neural stem cells. Aging Cell 2011, 10:466-482.
19. Brown W.R., Thore C.R. Review: cerebral microvascular pathology in ageing and neurodegeneration. Neuropathol. Appl. Neurobiol. 2011, 37:56-74.
20. Buga A.M., Sascau M., Pisoschi C., Herndon J.G., Kessler C., Popa-Wagner A. The genomic response of the ipsilateral and contralateral cortex to stroke in aged rats. J. Cell. Mol. Med. 2008, 12:2731-2753.
21. Buga A.M., Scholz C.J., Kumar S., Herndon J.G., Alexandru D., Cojocaru G.R., Dandekar T., Popa-Wagner A. Identification of new therapeutic targets by genome-wide analysis of gene expression in the ipsilateral cortex of aged rats after stroke. PLoS One 2012, 7:e50985.
22. Campuzano O., Castillo-Ruiz M.M., Acarin L., Castellano B., Gonzalez B. Increased levels of proinflammatory cytokines in the aged rat brain attenuate injury-induced cytokine response after excitotoxic damage. J. Neurosci. Res. 2009, 87:2484-2497.
23. Carswell H.V., Dominiczak A.F., Garcia-Segura L.M., Harada N., Hutchison J.B., Macrae I.M. Brain aromatase expression after experimental stroke: topography and time course. J. Steroid Biochem. Mol. Biol. 2005, 96:89-91.
24. Castellano J.F., Fletcher B.R., Kelley-Bell B., Kim D.H., Gallagher M., Rapp P.R. Age-related memory impairment is associated with disrupted multivariate epigenetic coordination in the hippocampus. PLoS One 2012, 7:e33249.
25. Cerciat M., Unkila M., Garcia-Segura L.M., Arevalo M.A. Selective estrogen receptor modulators decrease the production of interleukin-6 and interferon-gamma-inducible protein-10 by astrocytes exposed to inflammatory challenge in vitro. Glia 2010, 58:93-102.
26. Chaban V.V., Lakhter A.J., Micevych P. A membrane estrogen receptor mediates intracellular calcium release in astrocytes. Endocrinology 2004, 145:3788-3795.
27. Cheng J., Alkayed N.J., Hurn P.D. Deleterious effects of dihydrotestosterone on cerebral ischemic injury. J. Cereb. Blood Flow Metab. 2007, 27:1553-1562.
28. Cheng J., Hu W., Toung T.J., Zhang Z., Parker S.M., Roselli C.E., Hurn P.D. Age-dependent effects of testosterone in experimental stroke. J. Cereb. Blood Flow Metab. 2009, 29:486-494.
29. Chisholm N., Henderson M., Selvamani A., Park M.J., Dindot S., Miranda R., Sohrabji F. Histone methylation patterns in astrocytes are influenced by age following ischemia. Epigenetics 2015, 0.
30. Copen W.A., Schwamm L.H., Gonzalez R.G., Wu O., Harmath C.B., Schaefer P.W., Koroshetz W.J., Sorensen A.G. Ischemic stroke: effects of etiology and patient age on the time course of the core apparent diffusion coefficient. Radiology 2001, 221:27-34.
31. Cordeau P., Lalancette-Hebert M., Weng Y.C., Kriz J. Live imaging of neuroinflammation reveals sex and estrogen effects on astrocyte response to ischemic injury. Stroke 2008, 39:935-942.
32. Cotrina M.L., Nedergaard M. Astrocytes in the aging brain. J. Neurosci. Res. 2002, 67:1-10.
33. De Butte-Smith M., Nguyen A.P., Zukin R.S., Etgen A.M., Colbourne F. Failure of estradiol to ameliorate global ischemia-induced CA1 sector injury in middle-aged female gerbils. Brain Res. 2007, 1153:214-220.
34. Dhungana H., Malm T., Denes A., Valonen P., Wojciechowski S., Magga J., Savchenko E., Humphreys N., Grencis R., Rothwell N., Koistinaho J. Aging aggravates ischemic stroke-induced brain damage in mice with chronic peripheral infection. Aging Cell 2013, 12:842-850.
35. DiNapoli V.A., Huber J.D., Houser K., Li X., Rosen C.L. Early disruptions of the blood-brain barrier may contribute to exacerbated neuronal damage and prolonged functional recovery following stroke in aged rats. Neurobiol. Aging 2008, 29:753-764.
36. Djebaili M., Guo Q., Pettus E.H., Hoffman S.W., Stein D.G. The neurosteroids progesterone and allopregnanolone reduce cell death, gliosis, and functional deficits after traumatic brain injury in rats. J. Neurotrauma 2005, 22:106-118.
37. Dong P., Zhao J., Zhang Y., Dong J., Zhang L., Li D., Li L., Zhang X., Yang B., Lei W. Aging causes exacerbated ischemic brain injury and failure of sevoflurane post-conditioning: role of B-cell lymphoma-2. Neuroscience 2014, 275:2-11.
38. Dos Santos Sant'Anna G., Rostirola Elsner V., Moyses F., Reck Cechinel L., Agustini Lovatel G., Rodrigues Siqueira I. Histone deacetylase activity is altered in brain areas from aged rats. Neurosci. Lett. 2013, 556:152-154.
39. Dotson A.L., Zhu W., Libal N., Alkayed N.J., Offner H. Different immunological mechanisms govern protection from experimental stroke in young and older mice with recombinant TCR ligand therapy. Front. Cell. Neurosci. 2014, 8:284.
40. Dubal D.B., Kashon M.L., Pettigrew L.C., Ren J.M., Finklestein S.P., Rau S.W., Wise P.M. Estradiol protects against ischemic injury. J. Cereb. Blood Flow Metab. 1998, 18:1253-1258.
41. Duncan K.A., Moon J., Vartosis D., Zee I. Injury-induced expression of glial androgen receptor in the zebra finch brain. J. Neurotrauma 2013, 30:1919-1924.
42. Eng L.F., Ghirnikar R.S. GFAP and astrogliosis. Brain Pathol. 1994, 4:229-237.
43. Farrall A.J., Wardlaw J.M. Blood-brain barrier: ageing and microvascular disease-systematic review and meta-analysis. Neurobiol. Aging 2009, 30:337-352.
44. Figley C.R., Stroman P.W. The role(s) of astrocytes and astrocyte activity in neurometabolism, neurovascular coupling, and the production of functional neuroimaging signals. Eur. J. Neurosci. 2011, 33:577-588.
45. Fonarow G.C., Reeves M.J., Zhao X., Olson D.M., Smith E.E., Saver J.L., Schwamm L.H., Get With the Guidelines-Stroke Steering Committee and Investigators Age-related differences in characteristics, performance measures, treatment trends, and outcomes in patients with ischemic stroke. Circulation 2010, 121:879-891.
46. Fukuda M., Kanda T., Kamide N., Akutsu T., Sakai F. Gender differences in long-term functional outcome after first-ever ischemic stroke. Intern. Med. 2009, 48:967-973.
47. Garcia-Estrada J., Del Rio J.A., Luquin S., Soriano E., Garcia-Segura L.M. Gonadal hormones down-regulate reactive gliosis and astrocyte proliferation after a penetrating brain injury. Brain Res. 1993, 628:271-278.
48. Garcia-Estrada J., Luquin S., Fernandez A.M., Garcia-Segura L.M. Dehydroepiandrosterone, pregnenolone and sex steroids down-regulate reactive astroglia in the male rat brain after a penetrating brain injury. Int. J. Dev. Neurosci. 1999, 17:145-151.
49. Garcia-Segura L.M., Wozniak A., Azcoitia I., Rodriguez J.R., Hutchison R.E., Hutchison J.B. Aromatase expression by astrocytes after brain injury: implications for local estrogen formation in brain repair. Neuroscience 1999, 89:567-578.
50. Gargano J.W., Wehner S., Reeves M.J. Presenting symptoms and onset-to-arrival time in patients with acute stroke and transient ischemic attack. J. Stroke Cerebrovasc. Dis. 2011, 20:494-502.
51. Gattringer T., Ferrari J., Knoflach M., Seyfang L., Horner S., Niederkorn K., Culea V., Beitzke M., Lang W., Enzinger C., Fazekas F. Sex-related differences of acute stroke unit care: results from the Austrian stroke unit registry. Stroke 2014, 45:1632-1638.
52. Genis L., Davila D., Fernandez S., Pozo-Rodrigalvarez A., Martinez-Murillo R., Torres-Aleman I. Astrocytes Require Insulin-like Growth Factor I to Protect Neurons Against Oxidative Injury 2014, (F1000Res 3:28-28.v2. eCollection 2014).
53. Gibson C.L., Coomber B., Murphy S.P. Progesterone is neuroprotective following cerebral ischaemia in reproductively ageing female mice. Brain 2011, 134:2125-2133.
54. Giraud S.N., Caron C.M., Pham-Dinh D., Kitabgi P., Nicot A.B. Estradiol inhibits ongoing autoimmune neuroinflammation and NFkappaB-dependent CCL2 expression in reactive astrocytes. Proc. Natl. Acad. Sci. U. S. A. 2010, 107:8416-8421.
55. Go A.S., Mozaffarian D., Roger V.L., Benjamin E.J., Berry J.D., Blaha M.J., Dai S., Ford E.S., Fox C.S., Franco S., Fullerton H.J., Gillespie C., Hailpern S.M., Heit J.A., Howard V.J., Huffman M.D., Judd S.E., Kissela B.M., Kittner S.J., Lackland D.T., Lichtman J.H., Lisabeth L.D., Mackey R.H., Magid D.J., Marcus G.M., Marelli A., Matchar D.B., McGuire D.K., Mohler E.R., Moy C.S., Mussolino M.E., Neumar R.W., Nichol G., Pandey D.K., Paynter N.P., Reeves M.J., Sorlie P.D., Stein J., Towfighi A., Turan T.N., Virani S.S., Wong N.D., Woo D., Turner M.B., American Heart Association Statistics Committee and Stroke Statistics Subcommittee Heart disease and stroke statistics-2014 update: a report from the American Heart Association. Circulation 2014, 129:e28-e292.
56. Gulinello M., Lebesgue D., Jover-Mengual T., Zukin R.S., Etgen A.M. Acute and chronic estradiol treatments reduce memory deficits induced by transient global ischemia in female rats. Horm. Behav. 2006, 49:246-260.
57. Guo J., Duckles S.P., Weiss J.H., Li X., Krause D.N. 17Beta-estradiol prevents cell death and mitochondrial dysfunction by an estrogen receptor-dependent mechanism in astrocytes after oxygen-glucose deprivation/reperfusion. Free Radic. Biol. Med. 2012, 52:2151-2160.
58. Hall E.D., Pazara K.E., Linseman K.L. Sex differences in postischemic neuronal necrosis in gerbils. J. Cereb. Blood Flow Metab. 1991, 11:292-298.
59. Inagaki T., Etgen A.M. Neuroprotective action of acute estrogens: animal models of brain ischemia and clinical implications. Steroids 2013, 78:597-606.
60. Jiang T., Cadenas E. Astrocytic metabolic and inflammatory changes as a function of age. Aging Cell 2014, 13:1059-1067.
61. 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. 2007, 10:331-339.
62. Juraska J.M., Lowry N.C. Neuroanatomical changes associated with cognitive aging. Curr. Top. Behav. Neurosci. 2012, 10:137-162.
63. Kapral M.K., Fang J., Hill M.D., Silver F., Richards J., Jaigobin C., Cheung A.M., Investigators of the Registry of the Canadian Stroke Network Sex differences in stroke care and outcomes: results from the Registry of the Canadian Stroke Network. Stroke 2005, 36:809-814.
64. Kelly K.A., Li X., Tan Z., VanGilder R.L., Rosen C.L., Huber J.D. NOX2 inhibition with apocynin worsens stroke outcome in aged rats. Brain Res. 2009, 1292:165-172.
65. Kim Y.D., Sohn N.W., Kang C., Soh Y. DNA array reveals altered gene expression in response to focal cerebral ischemia. Brain Res. Bull. 2002, 58:491-498.
66. Kim J.B., Piao C.S., Lee K.W., Han P.L., Ahn J.I., Lee Y.S., Lee J.K. Delayed genomic responses to transient middle cerebral artery occlusion in the rat. J. Neurochem. 2004, 89:1271-1282.
67. Kuo J., Hamid N., Bondar G., Prossnitz E.R., Micevych P. Membrane estrogen receptors stimulate intracellular calcium release and progesterone synthesis in hypothalamic astrocytes. J. Neurosci. 2010, 30:12950-12957.
68. Kuo J., Hamid N., Bondar G., Dewing P., Clarkson J., Micevych P. Sex differences in hypothalamic astrocyte response to estradiol stimulation. Biol. Sex Differ. 2010, 1. (7-6410-1-7).
69. Kury P., Schroeter M., Jander S. Transcriptional response to circumscribed cortical brain ischemia: spatiotemporal patterns in ischemic vs. remote non-ischemic cortex. Eur. J. Neurosci. 2004, 19:1708-1720.
70. Latour A., Grintal B., Champeil-Potokar G., Hennebelle M., Lavialle M., Dutar P., Potier B., Billard J.M., Vancassel S., Denis I. Omega-3 fatty acids deficiency aggravates glutamatergic synapse and astroglial aging in the rat hippocampal CA1. Aging Cell 2013, 12:76-84.
71. Lee E.S., Sidoryk M., Jiang H., Yin Z., Aschner M. Estrogen and tamoxifen reverse manganese-induced glutamate transporter impairment in astrocytes. J. Neurochem. 2009, 110:530-544.
72. Leon R.L., Li X., Huber J.D., Rosen C.L. Worsened outcome from middle cerebral artery occlusion in aged rats receiving 17beta-estradiol. Endocrinology 2012, 153:3386-3393.
73. Lewis D.K., Johnson A.B., Stohlgren S., Harms A., Sohrabji F. Effects of estrogen receptor agonists on regulation of the inflammatory response in astrocytes from young adult and middle-aged female rats. J. Neuroimmunol. 2008, 195:47-59.
74. Lewis D.K., Thomas K.T., Selvamani A., Sohrabji F. Age-related severity of focal ischemia in female rats is associated with impaired astrocyte function. Neurobiol. Aging 2012, 33. (1123.e1-1123.16).
75. Li X., Blizzard K.K., Zeng Z., DeVries A.C., Hurn P.D., McCullough L.D. Chronic behavioral testing after focal ischemia in the mouse: functional recovery and the effects of gender. Exp. Neurol. 2004, 187:94-104.
76. Liu M., Hurn P.D., Roselli C.E., Alkayed N.J. Role of P450 aromatase in sex-specific astrocytic cell death. J. Cereb. Blood Flow Metab. 2007, 27:135-141.
77. Liu M., Oyarzabal E.A., Yang R., Murphy S.J., Hurn P.D. A novel method for assessing sex-specific and genotype-specific response to injury in astrocyte culture. J. Neurosci. Methods 2008, 171:214-217.
78. Liu F., Yuan R., Benashski S.E., McCullough L.D. Changes in experimental stroke outcome across the life span. J. Cereb. Blood Flow Metab. 2009, 29:792-802.
79. 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 2014, 62:2022-2033.
80. Liu F., Ni J.J., Huang J.J., Kou Z.W., Sun F.Y. VEGF overexpression enhances the accumulation of phospho-S292 MeCP2 in reactive astrocytes in the adult rat striatum following cerebral ischemia. Brain Res. 2015, 1599:32-43.
81. Loram L.C., Sholar P.W., Taylor F.R., Wiesler J.L., Babb J.A., Strand K.A., Berkelhammer D., Day H.E., Maier S.F., Watkins L.R. Sex and estradiol influence glial pro-inflammatory responses to lipopolysaccharide in rats. Psychoneuroendocrinology 2012, 37:1688-1699.
82. Lu T., Pan Y., Kao S.Y., Li C., Kohane I., Chan J., Yankner B.A. Gene regulation and DNA damage in the ageing human brain. Nature 2004, 429:883-891.
83. Ma Y.L., Qin P., Feng D.Y., Li Y., Zhang L.X., Liu Z.Y., Yin A.Q., Tang W.H., Dong H.L., Meng L.Z., Hou W.G., Xiong L.Z. Estrogen regulates the expression of Ndrg2 in astrocytes. Brain Res. 2014, 1569:1-8.
84. Manwani B., Liu F., Xu Y., Persky R., Li J., McCullough L.D. Functional recovery in aging mice after experimental stroke. Brain Behav. Immun. 2011, 25:1689-1700.
85. Manwani B., Liu F., Scranton V., Hammond M.D., Sansing L.H., McCullough L.D. Differential effects of aging and sex on stroke induced inflammation across the lifespan. Exp. Neurol. 2013, 249:120-131.
86. McCullough L.D., Blizzard K., Simpson E.R., Oz O.K., Hurn P.D. Aromatase cytochrome P450 and extragonadal estrogen play a role in ischemic neuroprotection. J. Neurosci. 2003, 23:8701-8705.
87. McLay R.N., Kastin A.J., Zadina J.E. Passage of interleukin-1-beta across the blood-brain barrier is reduced in aged mice: a possible mechanism for diminished fever in aging. Neuroimmunomodulation 2000, 8:148-153.
88. Miao J., Shen L.H., Tang Y.H., Wang Y.T., Tao M.X., Jin K.L., Zhao Y.J., Yang G.Y. Overexpression of adiponectin improves neurobehavioral outcomes after focal cerebral ischemia in aged mice. CNS Neurosci. Ther. 2013, 19:969-977.
89. Micevych P.E., Chaban V., Ogi J., Dewing P., Lu J.K., Sinchak K. Estradiol stimulates progesterone synthesis in hypothalamic astrocyte cultures. Endocrinology 2007, 148:782-789.
90. Middeldorp J., Hol E.M. GFAP in health and disease. Prog. Neurobiol. 2011, 93:421-443.
91. Montagne A., Barnes S.R., Sweeney M.D., Halliday M.R., Sagare A.P., Zhao Z., Toga A.W., Jacobs R.E., Liu C.Y., Amezcua L., Harrington M.G., Chui H.C., Law M., Zlokovic B.V. Blood-brain barrier breakdown in the aging human hippocampus. Neuron 2015, 85:296-302.
92. Morizawa Y., Sato K., Takaki J., Kawasaki A., Shibata K., Suzuki T., Ohta S., Koizumi S. Cell-autonomous enhancement of glutamate-uptake by female astrocytes. Cell. Mol. Neurobiol. 2012, 32:953-956.
93. Neufeld G., Tessler S., Gitay-Goren H., Cohen T., Levi B.Z. Vascular endothelial growth factor and its receptors. Prog. Growth Factor Res. 1994, 5:89-97.
94. Orre M., Kamphuis W., Osborn L.M., Melief J., Kooijman L., Huitinga I., Klooster J., Bossers K., Hol E.M. Acute isolation and transcriptome characterization of cortical astrocytes and microglia from young and aged mice. Neurobiol. Aging 2014, 35:1-14.
95. Ovbiagele B., Goldstein L.B., Higashida R.T., Howard V.J., Johnston S.C., Khavjou O.A., Lackland D.T., Lichtman J.H., Mohl S., Sacco R.L., Saver J.L., Trogdon J.G., American Heart Association Advocacy Coordinating Committee and Stroke Council Forecasting the future of stroke in the United States: a policy statement from the American Heart Association and American Stroke Association. Stroke 2013, 44:2361-2375.
96. Pawlak J., Brito V., Kuppers E., Beyer C. Regulation of glutamate transporter GLAST and GLT-1 expression in astrocytes by estrogen. Brain Res. Mol. Brain Res. 2005, 138:1-7.
97. Pawlak J., Karolczak M., Krust A., Chambon P., Beyer C. Estrogen receptor-alpha is associated with the plasma membrane of astrocytes and coupled to the MAP/Src-kinase pathway. Glia 2005, 50:270-275.
98. Peleg S., Sananbenesi F., Zovoilis A., Burkhardt S., Bahari-Javan S., Agis-Balboa R.C., Cota P., Wittnam J.L., Gogol-Doering A., Opitz L., Salinas-Riester G., Dettenhofer M., Kang H., Farinelli L., Chen W., Fischer A. Altered histone acetylation is associated with age-dependent memory impairment in mice. Science 2010, 328:753-756.
99. Pelegri C., Canudas A.M., del Valle J., Casadesus G., Smith M.A., Camins A., Pallas M., Vilaplana J. Increased permeability of blood-brain barrier on the hippocampus of a murine model of senescence. Mech. Ageing Dev. 2007, 128:522-528.
100. Perez-Alvarez M.J., Maza Mdel C., Anton M., Ordonez L., Wandosell F. Post-ischemic estradiol treatment reduced glial response and triggers distinct cortical and hippocampal signaling in a rat model of cerebral ischemia. J. Neuroinflammation 2012, 9. (157-2094-9-157).
101. Petrea R.E., Beiser A.S., Seshadri S., Kelly-Hayes M., Kase C.S., Wolf P.A. Gender differences in stroke incidence and poststroke disability in the Framingham heart study. Stroke 2009, 40:1032-1037.
102. Pfrieger F.W. Role of glial cells in the formation and maintenance of synapses. Brain Res. Rev. 2010, 63:39-46.
103. Pineau I., Sun L., Bastien D., Lacroix S. Astrocytes initiate inflammation in the injured mouse spinal cord by promoting the entry of neutrophils and inflammatory monocytes in an IL-1 receptor/MyD88-dependent fashion. Brain Behav. Immun. 2010, 24:540-553.
104. Popa-Wagner A., Badan I., Walker L., Groppa S., Patrana N., Kessler C. Accelerated infarct development, cytogenesis and apoptosis following transient cerebral ischemia in aged rats. Acta Neuropathol. 2007, 113:277-293.
105. Ridet J.L., Malhotra S.K., Privat A., Gage F.H. Reactive astrocytes: cellular and molecular cues to biological function. Trends Neurosci. 1997, 20:570-577.
106. Rodriguez J.J., Yeh C.Y., Terzieva S., Olabarria M., Kulijewicz-Nawrot M., Verkhratsky A. Complex and region-specific changes in astroglial markers in the aging brain. Neurobiol. Aging 2014, 35:15-23.
107. Rosen C.L., Dinapoli V.A., Nagamine T., Crocco T. Influence of age on stroke outcome following transient focal ischemia. J. Neurosurg. 2005, 103:687-694.
108. Rusa R., Alkayed N.J., Crain B.J., Traystman R.J., Kimes A.S., London E.D., Klaus J.A., Hurn P.D. 17Beta-estradiol reduces stroke injury in estrogen-deficient female animals. Stroke 1999, 30:1665-1670.
109. Santos-Galindo M., Acaz-Fonseca E., Bellini M.J., Garcia-Segura L.M. Sex differences in the inflammatory response of primary astrocytes to lipopolysaccharide. Biol. Sex Differ. 2011, 2. (7-6410-2-7).
110. Scuderi C., Stecca C., Bronzuoli M.R., Rotili D., Valente S., Mai A., Steardo L. Sirtuin modulators control reactive gliosis in an in vitro model of Alzheimer's disease. Front. Pharmacol. 2014, 5:89.
111. Selvamani A., Sohrabji F. The neurotoxic effects of estrogen on ischemic stroke in older female rats is associated with age-dependent loss of insulin-like growth factor-1. J. Neurosci. 2010, 30:6852-6861.
112. Selvamani A., Sohrabji F. Reproductive age modulates the impact of focal ischemia on the forebrain as well as the effects of estrogen treatment in female rats. Neurobiol. Aging 2010, 31:1618-1628.
113. Selvamani A., Williams M.H., Miranda R.C., Sohrabji F. Circulating miRNA profiles provide a biomarker for severity of stroke outcomes associated with age and sex in a rat model. Clin. Sci. (Lond.) 2014, 127:77-89.
114. Shapira S., Sapir M., Wengier A., Grauer E., Kadar T. Aging has a complex effect on a rat model of ischemic stroke. Brain Res. 2002, 925:148-158.
115. Shen Y., Gao H., Shi X., Wang N., Ai D., Li J., Ouyang L., Yang J., Tian Y., Lu J. Glutamine synthetase plays a role in d-galactose-induced astrocyte aging in vitro and in vivo. Exp. Gerontol. 2014, 58:166-173.
116. Sieber M.W., Guenther M., Jaenisch N., Albrecht-Eckardt D., Kohl M., Witte O.W., Frahm C. Age-specific transcriptional response to stroke. Neurobiol. Aging 2014, 35:1744-1754.
117. Simpkins J.W., Rajakumar G., Zhang Y.Q., Simpkins C.E., Greenwald D., Yu C.J., Bodor N., Day A.L. Estrogens may reduce mortality and ischemic damage caused by middle cerebral artery occlusion in the female rat. J. Neurosurg. 1997, 87:724-730.
118. Sofroniew M.V. Multiple roles for astrocytes as effectors of cytokines and inflammatory mediators. Neuroscientist 2014, 20:160-172.
119. Sofroniew M.V., Vinters H.V. Astrocytes: biology and pathology. Acta Neuropathol. 2010, 119:7-35.
120. Sohrabji F. Estrogen-IGF-1 interactions in neuroprotection: ischemic stroke as a case study. Front. Neuroendocrinol. 2015, 36C:1-14.
121. Spence R.D., Hamby M.E., Umeda E., Itoh N., Du S., Wisdom A.J., Cao Y., Bondar G., Lam J., Ao Y., Sandoval F., Suriany S., Sofroniew M.V., Voskuhl R.R. Neuroprotection mediated through estrogen receptor-alpha in astrocytes. Proc. Natl. Acad. Sci. U. S. A. 2011, 108:8867-8872.
122. Starkov A.A., Chinopoulos C., Fiskum G. Mitochondrial calcium and oxidative stress as mediators of ischemic brain injury. Cell Calcium 2004, 36:257-264.
123. Stipursky J., Romao L., Tortelli V., Neto V.M., Gomes F.C. Neuron-glia signaling: implications for astrocyte differentiation and synapse formation. Life Sci. 2011, 89:524-531.
124. 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. 2003, 111:1843-1851.
125. Suzuki K., Ikegaya Y., Matsuura S., Kanai Y., Endou H., Matsuki N. Transient upregulation of the glial glutamate transporter GLAST in response to fibroblast growth factor, insulin-like growth factor and epidermal growth factor in cultured astrocytes. J. Cell Sci. 2001, 114:3717-3725.
126. Suzuki T., Bramlett H.M., Dietrich W.D. The importance of gender on the beneficial effects of posttraumatic hypothermia. Exp. Neurol. 2003, 184:1017-1026.
127. Tan Z., Li X., Kelly K.A., Rosen C.L., Huber J.D. Plasminogen activator inhibitor type 1 derived peptide, EEIIMD, diminishes cortical infarct but fails to improve neurological function in aged rats following middle cerebral artery occlusion. Brain Res. 2009, 1281:84-90.
128. Tennant K.A., Kerr A.L., Adkins D.L., Donlan N., Thomas N., Kleim J.A., Jones T.A. Age-dependent reorganization of peri-infarct "premotor" cortex with task-specific rehabilitative training in mice. Neurorehabil. Neural Repair 2014, 29(2):193-202.
129. Towfighi A., Saver J.L., Engelhardt R., Ovbiagele B. A midlife stroke surge among women in the United States. Neurology 2007, 69:1898-1904.
130. Uchida M., Palmateer J.M., Herson P.S., DeVries A.C., Cheng J., Hurn P.D. Dose-dependent effects of androgens on outcome after focal cerebral ischemia in adult male mice. J. Cereb. Blood Flow Metab. 2009, 29:1454-1462.
131. Ueno M., Akiguchi I., Yagi H., Naiki H., Fujibayashi Y., Kimura J., Takeda T. Age-related changes in barrier function in mouse brain I. Accelerated age-related increase of brain transfer of serum albumin in accelerated senescence prone SAM-P/8 mice with deficits in learning and memory. Arch. Gerontol. Geriatr. 1993, 16:233-248.
132. Vagnerova K., Liu K., Ardeshiri A., Cheng J., Murphy S.J., Hurn P.D., Herson P.S. Poly (ADP-ribose) polymerase-1 initiated neuronal cell death pathway-do androgens matter?. Neuroscience 2010, 166:476-481.
133. Venturelli S., Berger A., Bocker A., Busch C., Weiland T., Noor S., Leischner C., Schleicher S., Mayer M., Weiss T.S., Bischoff S.C., Lauer U.M., Bitzer M. Resveratrol as a pan-HDAC inhibitor alters the acetylation status of histone [corrected] proteins in human-derived hepatoblastoma cells. PLoS One 2013, 8:e73097.
134. Verkhratsky A., Kirchhoff F. Glutamate-mediated neuronal-glial transmission. J. Anat. 2007, 210:651-660.
135. Vorbrodt A.W., Dobrogowska D.H., Meeker H.C., Carp R.I. Immunogold study of regional differences in the distribution of glucose transporter (GLUT-1) in mouse brain associated with physiological and accelerated aging and scrapie infection. J. Neurocytol. 1999, 28:711-719.
136. Wagner A.K., Bayir H., Ren D., Puccio A., Zafonte R.D., Kochanek P.M. Relationships between cerebrospinal fluid markers of excitotoxicity, ischemia, and oxidative damage after severe TBI: the impact of gender, age, and hypothermia. J. Neurotrauma 2004, 21:125-136.
137. Wang Z., Tsai L.K., Munasinghe J., Leng Y., Fessler E.B., Chibane F., Leeds P., Chuang D.M. Chronic valproate treatment enhances postischemic angiogenesis and promotes functional recovery in a rat model of ischemic stroke. Stroke 2012, 43:2430-2436.
138. Wang C., Jie C., Dai X. Possible roles of astrocytes in estrogen neuroprotection during cerebral ischemia. Rev. Neurosci. 2014, 25:255-268.
139. Wong R., Renton C., Gibson C.L., Murphy S.J., Kendall D.A., Bath P.M., Progesterone Pre-Clinical Stroke Pooling Project Collaboration Progesterone treatment for experimental stroke: an individual animal meta-analysis. J. Cereb. Blood Flow Metab. 2013, 33:1362-1372.
140. Xia W., Han J., Huang G., Ying W. Inflammation in ischaemic brain injury: current advances and future perspectives. Clin. Exp. Pharmacol. Physiol. 2010, 37:253-258.
141. Xu X., Zhan M., Duan W., Prabhu V., Brenneman R., Wood W., Firman J., Li H., Zhang P., Ibe C., Zonderman A.B., Longo D.L., Poosala S., Becker K.G., Mattson M.P. Gene expression atlas of the mouse central nervous system: impact and interactions of age, energy intake and gender. Genome Biol. 2007, 8:R234.
142. Yang Y., Rosenberg G.A. Blood-brain barrier breakdown in acute and chronic cerebrovascular disease. Stroke 2011, 42:3323-3328.
143. Yang X.J., Seto E. HATs and HDACs: from structure, function and regulation to novel strategies for therapy and prevention. Oncogene 2007, 26:5310-5318.
144. Yenari M.A., Han H.S. Neuroprotective mechanisms of hypothermia in brain ischaemia. Nat. Rev. Neurosci. 2012, 13:267-278.
145. 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. 2012, 32:6391-6410.
146. Zhang X.M., Zhu S.W., Duan R.S., Mohammed A.H., Winblad B., Zhu J. Gender differences in susceptibility to kainic acid-induced neurodegeneration in aged C57BL/6 mice. Neurotoxicology 2008, 29:406-412.
147. Zhang Q.G., Wang R., Tang H., Dong Y., Chan A., Sareddy G.R., Vadlamudi R.K., Brann D.W. Brain-derived estrogen exerts anti-inflammatory and neuroprotective actions in the rat hippocampus. Mol. Cell. Endocrinol. 2014, 389:84-91.
148. 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 2010, 5:e14401.
149. 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. 2013, 33:600-611.
150. Zwain I.H., Yen S.S. Neurosteroidogenesis in astrocytes, oligodendrocytes, and neurons of cerebral cortex of rat brain. Endocrinology 1999, 140:3843-3852.