Interactions between age, sex, and hormones in experimental ischemic stroke

Neurochemistry International

Volumn 61, Issue 8, 2012, Pages 1255-1265

  Liu, Fudong ^a   McCullough, Louise D ^a  

^a UNIVERSITY OF CONNECTICUT HEALTH CENTER   (United States)

Author keywords

Aging; Cerebral ischemia; Hormones; Sex differences; Stroke

Indexed keywords

ANDROGEN; ESTROGEN; SEX HORMONE;

AGE; AGING; ARTICLE; BRAIN ISCHEMIA; HORMONE SUBSTITUTION; HUMAN; LIFESPAN; NEUROPROTECTION; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; SEX; SEX DIFFERENCE; X CHROMOSOME;

EID: 84870290896     PISSN: 01970186     EISSN: 18729754     Source Type: Journal    
DOI: 10.1016/j.neuint.2012.10.003     Document Type: Short Survey

References (203)

1. I. Agartz, J. Saaf, L.O. Wahlund, and L. Wetterberg Quantitative estimations of cerebrospinal fluid spaces and brain regions in healthy controls using computer-assisted tissue classification of magnetic resonance images: relation to age and sex Magn. Reson. Imaging 10 2 1992 217 226
2. E. Ahlbom, L. Grandison, E. Bonfoco, B. Zhivotovsky, and S. Ceccatelli Androgen treatment of neonatal rats decreases susceptibility of cerebellar granule neurons to oxidative stress in vitro Eur. J. Neurosci. 11 4 1999 1285 1291
3. E. Ahlbom, G.S. Prins, and S. Ceccatelli Testosterone protects cerebellar granule cells from oxidative stress-induced cell death through a receptor mediated mechanism Brain Res. 892 2 2001 255 262
4. L.S. Allen, M. Hines, J.E. Shryne, and R.A. Gorski Two sexually dimorphic cell groups in the human brain J. Neurosci. 9 2 1989 497 506
5. M.A. Altinoz, and R. Korkmaz NF-kappaB, macrophage migration inhibitory factor and cyclooxygenase-inhibitions as likely mechanisms behind the acetaminophen- and NSAID-prevention of the ovarian cancer Neoplasma 51 4 2004 239 247
6. D. Amantea, R. Russo, G. Bagetta, and M.T. Corasaniti From clinical evidence to molecular mechanisms underlying neuroprotection afforded by estrogens Pharmacol. Res. 52 2 2005 119 132
7. P.J. Andreason, A.J. Zametkin, A.C. Guo, P. Baldwin, and R.M. Cohen Gender-related differences in regional cerebral glucose metabolism in normal volunteers Psychiatry Res. 51 2 1994 175 183
8. V.N. Anisimov, T.S. Piskunova, I.G. Popovich, M.A. Zabezhinski, M.L. Tyndyk, P.A. Egormin, M.V. Yurova, S.V. Rosenfeld, A.V. Semenchenko, and I.G. Kovalenko Gender differences in metformin effect on aging, life span and spontaneous tumorigenesis in 129/Sv mice Aging (Albany NY) 2 12 2010 945 958
9. E.C. Anyanwu Neurochemical changes in the aging process: implications in medication in the elderly Sci. World J. 7 2007 1603 1610
10. P. Appelros, B. Stegmayr, and A. Terent Sex differences in stroke epidemiology: a systematic review Stroke 40 4 2009 1082 1090
11. T.V. Arumugam, T.M. Phillips, A. Cheng, C.H. Morrell, M.P. Mattson, and R. Wan Age and energy intake interact to modify cell stress pathways and stroke outcome Ann. Neurol. 67 1 2010 41 52
12. N.P. Azari, S.I. Rapoport, C.L. Grady, C. DeCarli, J.V. Haxby, M.B. Schapiro, and B. Horwitz Gender differences in correlations of cerebral glucose metabolic rates in young normal adults Brain Res. 574 1-2 1992 198 208
13. I. Badan, I. Dinca, B. Buchhold, Y. Suofu, L. Walker, M. Gratz, D. Platt, C.H. Kessler, and A. Popa-Wagner Accelerated accumulation of N- and C-terminal beta APP fragments and delayed recovery of microtubule-associated protein 1B expression following stroke in aged rats Eur. J. Neurosci. 19 8 2004 2270 2280
14. K. Bala, B.C. Tripathy, and D. Sharma Neuroprotective and anti-ageing effects of curcumin in aged rat brain regions Biogerontology 7 2 2006 81 89
15. N.Z. Baquer, A. Taha, P. Kumar, P. McLean, S.M. Cowsik, R.K. Kale, R. Singh, and D. Sharma A metabolic and functional overview of brain aging linked to neurological disorders Biogerontology 10 4 2009 377 413
16. E. Barrett-Connor, and T.L. Bush Estrogen and coronary heart disease in women JAMA 265 14 1991 1861 1867
17. S. Basaria, A.D. Coviello, T.G. Travison, T.W. Storer, W.R. Farwell, A.M. Jette, R. Eder, S. Tennstedt, J. Ulloor, and A. Zhang Adverse events associated with testosterone administration N. Engl. J. Med. 363 2 2010 109 122
18. L.R. Baxter Jr.; J.C. Mazziotta, M.E. Phelps, C.E. Selin, B.H. Guze, and L. Fairbanks Cerebral glucose metabolic rates in normal human females versus normal males Psychiatry Res. 21 3 1987 237 245
19. C. Bertoni-Freddari, E. Mocchegiani, M. Malavolta, T. Casoli, G. Di Stefano, and P. Fattoretti Synaptic and mitochondrial physiopathologic changes in the aging nervous system and the role of zinc ion homeostasis Mech. Ageing Dev. 127 6 2006 590 596
20. E. Bona, H. Hagberg, E.M. Loberg, R. Bagenholm, and M. Thoresen Protective effects of moderate hypothermia after neonatal hypoxia-ischemia: short- and long-term outcome Pediatr. Res. 43 6 1998 738 745
21. M.G. Bousser Estrogens, migraine, and stroke Stroke 35 11 (Suppl. 1) 2004 2652 2656
22. H. Bowen, T.D. Mitchell, and R.B. Harris Method of leptin dosing, strain, and group housing influence leptin sensitivity in high-fat-fed weanling mice Am. J. Physiol. Regul. Integr. Comp. Physiol. 284 1 2003 R87 R100
23. K.J. Brackley, M.M. Ramsay, F. Broughton Pipkin, and P.C. Rubin The effect of the menstrual cycle on human cerebral blood flow: studies using Doppler ultrasound Ultrasound Obstet. Gynecol. 14 1 1999 52 57
24. R.D. Brown, J.P. Whisnant, J.D. Sicks, W.M. O'Fallon, and D.O. Wiebers Stroke incidence, prevalence, and survival: secular trends in Rochester, Minnesota, through 1989 Stroke 27 3 1996 373 380
25. D.M. Caspary, T.M. Holder, L.F. Hughes, J.C. Milbrandt, R.M. McKernan, and D.K. Naritoku Age-related changes in GABA(A) receptor subunit composition and function in rat auditory system Neuroscience 93 1 1999 307 312
26. K.L. Chambliss, and P.W. Shaul Estrogen modulation of endothelial nitric oxide synthase Endocr. Rev. 23 5 2002 665 686
27. Y. Chen, and F.Y. Sun Age-related decrease of striatal neurogenesis is associated with apoptosis of neural precursors and newborn neurons in rat brain after ischemia Brain Res. 1166 2007 9 19
28. J.L. Cheong, and F.M. Cowan Neonatal arterial ischaemic stroke: obstetric issues Semin. Fetal Neonatal Med. 14 5 2009 267 271
29. W. Cookson, L. Liang, G. Abecasis, M. Moffatt, and M. Lathrop Mapping complex disease traits with global gene expression Nat. Rev. Genet. 10 3 2009 184 194
30. M.P. Corcoran, M. Meydani, A.H. Lichtenstein, E.J. Schaefer, A. Dillard, and S. Lamon-Fava Sex hormone modulation of proinflammatory cytokine and C-reactive protein expression in macrophages from older men and postmenopausal women J. Endocrinol. 206 2 2010 217 224
31. F. Correa, M. Gauberti, J. Parcq, R. Macrez, Y. Hommet, P. Obiang, M. Hernangomez, A. Montagne, G. Liot, and C. Guaza Tissue plasminogen activator prevents white matter damage following stroke J. Exp. Med. 208 6 2011 1229 1242
32. V. Darsalia, U. Heldmann, O. Lindvall, and Z. Kokaia Stroke-induced neurogenesis in aged brain Stroke 36 8 2005 1790 1795
33. C. DeCarli, J. Massaro, D. Harvey, J. Hald, M. Tullberg, R. Au, A. Beiser, R. D'Agostino, and P.A. Wolf Measures of brain morphology and infarction in the framingham heart study: establishing what is normal Neurobiol. Aging 26 4 2005 491 510
34. M.D. Devous Sr.; E.M. Stokely, H.H. Chehabi, and F.J. Bonte Normal distribution of regional cerebral blood flow measured by dynamic single-photon emission tomography J. Cereb. Blood Flow Metab. 6 1 1986 95 104
35. V.A. DiNapoli, J.D. Huber, K. Houser, X. Li, and C.L. Rosen Early disruptions of the blood-brain barrier may contribute to exacerbated neuronal damage and prolonged functional recovery following stroke in aged rats Neurobiol. Aging 29 5 2008 753 764
36. U. Dirnagl, R.P. Simon, and J.M. Hallenbeck Ischemic tolerance and endogenous neuroprotection Trends Neurosci. 26 5 2003 248 254
37. K.L. Double, G.M. Halliday, J.J. Kril, J.A. Harasty, K. Cullen, W.S. Brooks, H. Creasey, and G.A. Broe Topography of brain atrophy during normal aging and Alzheimer's disease Neurobiol. Aging 17 4 1996 513 521
38. D.B. Dubal, and P.M. Wise Neuroprotective effects of estradiol in middle-aged female rats Endocrinology 142 1 2001 43 48
39. D.B. Dubal, P.J. Shughrue, M.E. Wilson, I. Merchenthaler, and P.M. Wise Estradiol modulates bcl-2 in cerebral ischemia: a potential role for estrogen receptors J. Neurosci. 19 15 1999 6385 6393
40. D.B. Dubal, H. Zhu, J. Yu, S.W. Rau, P.J. Shughrue, I. Merchenthaler, M.S. Kindy, and P.M. Wise Estrogen receptor alpha, not beta, is a critical link in estradiol-mediated protection against brain injury Proc. Natl. Acad. Sci. USA 98 4 2001 1952 1957
41. C.N. Epperson, K. Haga, G.F. Mason, E. Sellers, R. Gueorguieva, W. Zhang, E. Weiss, D.L. Rothman, and J.H. Krystal Cortical gamma-aminobutyric acid levels across the menstrual cycle in healthy women and those with premenstrual dysphoric disorder: a proton magnetic resonance spectroscopy study Arch. Gen. Psychiatry 59 9 2002 851 858
42. G. Esposito, J.D. Van Horn, D.R. Weinberger, and K.F. Berman Gender differences in cerebral blood flow as a function of cognitive state with PET J. Nucl. Med. 37 4 1996 559 564
43. M.Y. Farhat, M.C. Lavigne, and P.W. Ramwell The vascular protective effects of estrogen FASEB J. 10 5 1996 615 624
44. J.Z. Fields, and J.H. Gordon Estrogen inhibits the dopaminergic supersensitivity induced by neuroleptics Life Sci. 30 3 1982 229 234
45. P.A. Filipek, C. Richelme, D.N. Kennedy, and V.S. Caviness Jr. The young adult human brain: an MRI-based morphometric analysis Cereb. Cortex 4 4 1994 344 360
46. A. Fromm, U. Waje-Andreassen, L. Thomassen, and H. Naess Comparison between ischemic stroke patients <50 years and ≥50 years admitted to a single centre: the Bergen stroke study Stroke Res. Treat. 2011 2011 183256
47. C.A. Frye, and C.M. McCormick Androgens are neuroprotective in the dentate gyrus of adrenalectomized female rats Stress 3 3 2000 185 194
48. M. Fukuda, T. Kanda, N. Kamide, T. Akutsu, and F. Sakai Gender differences in long-term functional outcome after first-ever ischemic stroke Intern. Med. 48 12 2009 967 973
49. H.J. Fullerton, S.C. Johnston, and W.S. Smith Arterial dissection and stroke in children Neurology 57 7 2001 1155 1160
50. H.J. Fullerton, Y.W. Wu, S. Zhao, and S.C. Johnston Risk of stroke in children: ethnic and gender disparities Neurology 61 2 2003 189 194
51. K.F. Gangar, S. Vyas, M. Whitehead, D. Crook, H. Meire, and S. Campbell Pulsatility index in internal carotid artery in relation to transdermal oestradiol and time since menopause Lancet 338 8771 1991 839 842
52. J.N. Giedd, J.W. Snell, N. Lange, J.C. Rajapakse, B.J. Casey, P.L. Kozuch, A.C. Vaituzis, Y.C. Vauss, S.D. Hamburger, and D. Kaysen Quantitative magnetic resonance imaging of human brain development: ages 4-18 Cereb. Cortex 6 4 1996 551 560
53. L. Gimenez-Llort, L. Arranz, I. Mate, and M. De la Fuente Gender-specific neuroimmunoendocrine aging in a triple-transgenic 3xTg-AD mouse model for Alzheimer's disease and its relation with longevity NeuroImmunoModulation 15 4-6 2008 331 343
54. M.D. Ginsberg Neuroprotection for ischemic stroke: past, present and future Neuropharmacology 55 3 2008 363 389
55. E.L. Glader, B. Stegmayr, B. Norrving, A. Terent, K. Hulter-Asberg, P.O. Wester, and K. Asplund Sex differences in management and outcome after stroke: a Swedish national perspective Stroke 34 8 2003 1970 1975
56. J.M. Goldstein, L.J. Seidman, N.J. Horton, N. Makris, D.N. Kennedy, V.S. Caviness Jr.; S.V. Faraone, and M.T. Tsuang Normal sexual dimorphism of the adult human brain assessed by in vivo magnetic resonance imaging Cereb. Cortex 11 6 2001 490 497
57. M.R. Golomb, H.J. Fullerton, U. Nowak-Gottl, and G. Deveber Male predominance in childhood ischemic stroke: findings from the international pediatric stroke study Stroke 40 1 2009 52 57
58. C.R. Gomez, S. Hirano, B.T. Cutro, S. Birjandi, H. Baila, V. Nomellini, and E.J. Kovacs Advanced age exacerbates the pulmonary inflammatory response after lipopolysaccharide exposure Crit. Care Med. 35 1 2007 246 251
59. T. Goto, and M. Monk Regulation of X-chromosome inactivation in development in mice and humans Microbiol. Mol. Biol. Rev. 62 2 1998 362 378
60. I.D. Grachev, and A.V. Apkarian Anxiety in healthy humans is associated with orbital frontal chemistry Mol. Psychiatry 5 5 2000 482 488
61. R.C. Gur, R.E. Gur, W.D. Obrist, J.P. Hungerbuhler, D. Younkin, A.D. Rosen, B.E. Skolnick, and M. Reivich Sex and handedness differences in cerebral blood flow during rest and cognitive activity Science 217 4560 1982 659 661
62. R.C. Gur, B.I. Turetsky, M. Matsui, M. Yan, W. Bilker, P. Hughett, and R.E. Gur Sex differences in brain gray and white matter in healthy young adults: correlations with cognitive performance J. Neurosci. 19 10 1999 4065 4072
63. C.R. Guttmann, F.A. Jolesz, R. Kikinis, R.J. Killiany, M.B. Moss, T. Sandor, and M.S. Albert White matter changes with normal aging Neurology 50 4 1998 972 978
64. S. Haberman, R. Capildeo, and F.C. Rose Sex differences in the incidence of cerebrovascular disease J. Epidemiol. Community Health 35 1 1981 45 50
65. W. Hacke, M. Kaste, E. Bluhmki, M. Brozman, A. Davalos, D. Guidetti, V. Larrue, K.R. Lees, Z. Medeghri, and T. Machnig Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke N. Engl. J. Med. 359 13 2008 1317 1329
66. H. Hagberg, M.A. Wilson, H. Matsushita, C. Zhu, M. Lange, M. Gustavsson, M.F. Poitras, T.M. Dawson, V.L. Dawson, and F. Northington PARP-1 gene disruption in mice preferentially protects males from perinatal brain injury J. Neurochem. 90 5 2004 1068 1075
67. J. Hammond, Q. Le, C. Goodyer, M. Gelfand, M. Trifiro, and A. LeBlanc Testosterone-mediated neuroprotection through the androgen receptor in human primary neurons J. Neurochem. 77 5 2001 1319 1326
68. H.S. Han, and M.A. Yenari Cellular targets of brain inflammation in stroke Curr. Opin. Investig. Drugs 4 5 2003 522 529
69. J. Harasty, K.L. Double, G.M. Halliday, J.J. Kril, and D.A. McRitchie Language-associated cortical regions are proportionally larger in the female brain Arch. Neurol. 54 2 1997 171 176
70. N.R. Harris, and R.E. Rumbaut Age-related responses of the microcirculation to ischemia-reperfusion and inflammation Pathophysiology 8 1 2001 1 10
71. C. Hatakeyama, C.L. Anderson, C.L. Beever, M.S. Penaherrera, C.J. Brown, and W.P. Robinson The dynamics of X-inactivation skewing as women age Clin. Genet. 66 4 2004 327 332
72. J. Hatazawa, R.A. Brooks, G. Di Chiro, and G. Campbell Global cerebral glucose utilization is independent of brain size: a PET study J. Comput. Assist. Tomogr. 11 4 1987 571 576
73. T. Hawk, Y.Q. Zhang, G. Rajakumar, A.L. Day, and J.W. Simpkins Testosterone increases and estradiol decreases middle cerebral artery occlusion lesion size in male rats Brain Res. 796 1-2 1998 296 298
74. E. Heard, and C.M. Disteche Dosage compensation in mammals: fine-tuning the expression of the X chromosome Genes Dev. 20 14 2006 1848 1867
75. J.Y. Ho, M.J. Chen, W.H. Sheu, Y.C. Yi, A.C. Tsai, H.F. Guu, and E.S. Ho Differential effects of oral conjugated equine estrogen and transdermal estrogen on atherosclerotic vascular disease risk markers and endothelial function in healthy postmenopausal women Hum. Reprod. 21 10 2006 2715 2720
76. M. Hollander, P.J. Koudstaal, M.L. Bots, D.E. Grobbee, A. Hofman, and M.M. Breteler Incidence, risk, and case fatality of first ever stroke in the elderly population. The Rotterdam study J. Neurol. Neurosurg. Psychiatry 74 3 2003 317 321
77. J.S. Hothersall, A. El-Hassan, P. McLean, and A.L. Greenbaum Age-related changes in enzymes of rat brain. 2. Redox systems linked to NADP and glutathione Enzyme 26 5 1981 271 276
78. P.D. Hurn, and I.M. Macrae Estrogen as a neuroprotectant in stroke J. Cereb. Blood Flow Metab. 20 4 2000 631 652
79. M. Ishikawa, D. Cooper, T.V. Arumugam, J.H. Zhang, A. Nanda, and D.N. Granger Platelet-leukocyte-endothelial cell interactions after middle cerebral artery occlusion and reperfusion J. Cereb. Blood Flow Metab. 24 8 2004 907 915
80. K. Jones, K.A. Johnson, J.A. Becker, P.A. Spiers, M.S. Albert, and B.L. Holman Use of singular value decomposition to characterize age and gender differences in SPECT cerebral perfusion J. Nucl. Med. 39 6 1998 965 973
81. J.A. Kaye, C. DeCarli, J.S. Luxenberg, and S.I. Rapoport The significance of age-related enlargement of the cerebral ventricles in healthy men and women measured by quantitative computed X-ray tomography J. Am. Geriatr. Soc. 40 3 1992 225 231
82. K.A. Kelly, X. Li, Z. Tan, R.L. VanGilder, C.L. Rosen, and J.D. Huber NOX2 inhibition with apocynin worsens stroke outcome in aged rats Brain Res. 1292 2009 165 172
83. A. Kharlamov, E. Kharlamov, and D.M. Armstrong Age-dependent increase in infarct volume following photochemically induced cerebral infarction: putative role of astroglia J. Gerontol. A: Biol. Sci. Med. Sci. 55 3 2000 B135 B141 Discussion: B142-B143
84. R.J. Killiany, D.S. Meier, and C.R. Guttmann Image processing: global and regional changes with age Top. Magn. Reson. Imaging 15 6 2004 349 353
85. M. Knoflach, B. Matosevic, M. Rucker, M. Furtner, A. Mair, G. Wille, A. Zangerle, P. Werner, J. Ferrari, and C. Schmidauer Functional recovery after ischemic stroke - a matter of age: data from the Austrian Stroke Unit Registry Neurology 78 4 2012 279 285
86. J. Krejza, M. Huba, Z. Mariak, and M. Owlasiuk Measurement of cerebral blood flow volume in healthy adults using color duplex sonography Stroke 31 8 2000 2026 2028
87. S. Krishnan, K.A. Intlekofer, L.K. Aggison, and S.L. Petersen Central role of TRAF-interacting protein in a new model of brain sexual differentiation Proc. Natl. Acad. Sci. USA 106 39 2009 16692 16697
88. J. Kucharczak, M.J. Simmons, Y. Fan, and C. Gelinas To be, or not to be: NF-kappaB is the answer - role of Rel/NF-kappaB in the regulation of apoptosis Oncogene 22 56 2003 8961 8982
89. D.E. Kuhl, E.J. Metter, W.H. Riege, and M.E. Phelps Effects of human aging on patterns of local cerebral glucose utilization determined by the [18F]fluorodeoxyglucose method J. Cereb. Blood Flow Metab. 2 2 1982 163 171
90. K.E. Latham X chromosome imprinting and inactivation in preimplantation mammalian embryos Trends Genet. 21 2 2005 120 127
91. J. Lenicek Krleza, V. Duranovic, L. Lujic, D. Coen Herak, V. Mejaski-Bosnjak, M. Nakic, and R. Zadro The burden of paediatric stroke and cerebrovascular disorders in Croatia Int. J. Stroke 4 5 2009 390 394
92. D.K. Lewis, K.T. Thomas, A. Selvamani, and F. Sohrabji Age-related severity of focal ischemia in female rats is associated with impaired astrocyte function Neurobiol. Aging 33 6 2012 1123.e1 1123.e16
93. J. Li, and L.D. McCullough Effects of AMP-activated protein kinase in cerebral ischemia J. Cereb. Blood Flow Metab. 30 3 2010 480 492
94. N. Li, X. Kong, R. Ye, Q. Yang, J. Han, and L. Xiong Age-related differences in experimental stroke: possible involvement of mitochondrial dysfunction and oxidative damage Rejuvenation Res. 14 3 2011 261 273
95. M. Liu, S. Dziennis, P.D. Hurn, and N.J. Alkayed Mechanisms of gender-linked ischemic brain injury Restor. Neurol. Neurosci. 27 3 2009 163 179
96. F. Liu, R. Yuan, S.E. Benashski, and L.D. McCullough Changes in experimental stroke outcome across the life span J. Cereb. Blood Flow Metab. 29 4 2009 792 802
97. F. Liu, P. Akella, S.E. Benashski, Y. Xu, and L.D. McCullough Expression of Na-K-Cl cotransporter and edema formation are age dependent after ischemic stroke Exp. Neurol. 224 2 2010 356 361
98. F. Liu, S.E. Benashski, R. Persky, Y. Xu, J. Li, and L.D. McCullough Age-related changes in AMP-activated protein kinase after stroke Age (Dordr.) 34 1 2011 157 168
99. F. Liu, S.E. Benashski, Y. Xu, M. Siegel, and L.D. McCullough Effects of chronic and acute oestrogen replacement therapy in aged animals after experimental stroke J. Neuroendocrinol. 24 2 2012 319 330
100. J.K. Lynch, D.G. Hirtz, G. DeVeber, and K.B. Nelson Report of the National Institute of Neurological Disorders and Stroke workshop on perinatal and childhood stroke Pediatrics 109 1 2002 116 123
101. A.M. Mabb, S.M. Wuerzberger-Davis, and S. Miyamoto PIASy mediates NEMO sumoylation and NF-kappaB activation in response to genotoxic stress Nat. Cell Biol. 8 9 2006 986 993
102. J.F. Maestre-Moreno, M.D. Fernandez-Perez, C. Arnaiz-Urrutia, A. Minguez, P. Navarrete-Navarro, and J. Martinez-Bosch Thrombolysis in stroke: inappropriate consideration of the 'window period' as the time available Rev. Neurol. 40 5 2005 274 278
103. A.K. Mantha, K. Moorthy, S.M. Cowsik, and N.Z. Baquer Membrane associated functions of neurokinin B (NKB) on Abeta (25-35) induced toxicity in aging rat brain synaptosomes Biogerontology 7 1 2006 19 33
104. B. Manwani, and L.D. McCullough Sexual dimorphism in ischemic stroke: lessons from the laboratory Womens Health (Lond. Engl.) 7 3 2011 319 339
105. M. Matsumae, R. Kikinis, I.A. Morocz, A.V. Lorenzo, T. Sandor, M.S. Albert, P.M. Black, and F.A. Jolesz Age-related changes in intracranial compartment volumes in normal adults assessed by magnetic resonance imaging J. Neurosurg. 84 6 1996 982 991
106. S.R. Mayoral, G. Omar, and A.A. Penn Sex differences in a hypoxia model of preterm brain damage Pediatr. Res. 66 3 2009 248 253
107. L.D. McCullough, and P.D. Hurn Estrogen and ischemic neuroprotection: an integrated view Trends Endocrinol. Metab. 14 5 2003 228 235
108. L.D. McCullough, N.J. Alkayed, R.J. Traystman, M.J. Williams, and P.D. Hurn Postischemic estrogen reduces hypoperfusion and secondary ischemia after experimental stroke Stroke 32 3 2001 796 802
109. L.D. McCullough, Z. Zeng, K.K. Blizzard, I. Debchoudhury, and P.D. Hurn Ischemic nitric oxide and poly (ADP-ribose) polymerase-1 in cerebral ischemia: male toxicity, female protection J. Cereb. Blood Flow Metab. 25 4 2005 502 512
110. M.E. Mendelsohn, and R.H. Karas The protective effects of estrogen on the cardiovascular system N. Engl. J. Med. 340 23 1999 1801 1811
111. B. Moosmann, and C. Behl The antioxidant neuroprotective effects of estrogens and phenolic compounds are independent from their estrogenic properties Proc. Natl. Acad. Sci. USA 96 16 1999 8867 8872
112. M. Morleo, and B. Franco Dosage compensation of the mammalian X chromosome influences the phenotypic variability of X-linked dominant male-lethal disorders J. Med. Genet. 45 7 2008 401 408
113. T. Moulin, L. Tatu, F. Vuillier, E. Berger, D. Chavot, and L. Rumbach Role of a stroke data bank in evaluating cerebral infarction subtypes: patterns and outcome of 1,776 consecutive patients from the Besancon stroke registry Cerebrovasc. Dis. 10 4 2000 261 271
114. D.G. Murphy, C. DeCarli, A.R. McIntosh, E. Daly, M.J. Mentis, P. Pietrini, J. Szczepanik, M.B. Schapiro, C.L. Grady, and B. Horwitz Sex differences in human brain morphometry and metabolism: an in vivo quantitative magnetic resonance imaging and positron emission tomography study on the effect of aging Arch. Gen. Psychiatry 53 7 1996 585 594
115. S.J. Murphy, L.D. McCullough, and J.M. Smith Stroke in the female: role of biological sex and estrogen ILAR J. 45 2 2004 147 159
116. S.A. Muwakkit, M. Majdalani, R. Hourani, R.A. Mahfouz, Z.K. Otrock, C. Bilalian, A.K. Chan, M. Abboud, and M.A. Mikati Inherited thrombophilia in childhood arterial stroke: data from Lebanon Pediatr. Neurol. 45 3 2011 155 158
117. M. Niewada, A. Kobayashi, P.A. Sandercock, B. Kaminski, and A. Czlonkowska Influence of gender on baseline features and clinical outcomes among 17,370 patients with confirmed ischaemic stroke in the international stroke trial Neuroepidemiology 24 3 2005 123 128
118. P. Nopoulos, M. Flaum, D. O'Leary, and N.C. Andreasen Sexual dimorphism in the human brain: evaluation of tissue volume, tissue composition and surface anatomy using magnetic resonance imaging Psychiatry Res. 98 1 2000 1 13
119. S. Normann, G. de Veber, M. Fobker, C. Langer, G. Kenet, T.J. Bernard, B. Fiedler, R. Strater, N.A. Goldenberg, and U. Nowak-Gottl Role of endogenous testosterone concentration in pediatric stroke Ann. Neurol. 66 6 2009 754 758
120. J.A. Ogeng'o, B.O. Olabu, A.N. Mburu, and S.R. Sinkeet Pediatric stroke in an African country J. Pediatr. Neurosci. 5 1 2010 22 24
121. K. Ohta, M. Iwai, K. Sato, N. Omori, I. Nagano, M. Shoji, and K. Abe Dissociative increase of oligodendrocyte progenitor cells between young and aged rats after transient cerebral ischemia Neurosci. Lett. 335 3 2003 159 162
122. G. Orlandi, A. Gelli, S. Fanucchi, G. Tognoni, G. Acerbi, and L. Murri Prevalence of stroke and transient ischaemic attack in the elderly population of an Italian rural community Eur. J. Epidemiol. 18 9 2003 879 882
123. J. Ortiz, F. Artigas, and E. Gelpi Serotonergic status in human blood Life Sci. 43 12 1988 983 990
124. B. Pakkenberg, and H.J. Gundersen Neocortical neuron number in humans: effect of sex and age J. Comp. Neurol. 384 2 1997 312 320
125. A. Panda, A. Arjona, E. Sapey, F. Bai, E. Fikrig, R.R. Montgomery, J.M. Lord, and A.C. Shaw Human innate immunosenescence. causes and consequences for immunity in old age Trends Immunol. 30 7 2009 325 333
126. Y. Park, Y. Kim, and D. Stanley Cellular immunosenescence in adult male crickets, Gryllus assimilis Arch. Insect Biochem. Physiol. 76 4 2011 185 194
127. T.J. Passe, P. Rajagopalan, L.A. Tupler, C.E. Byrum, J.R. MacFall, and K.R. Krishnan Age and sex effects on brain morphology Prog. Neuropsychopharmacol. Biol. Psychiatry 21 8 1997 1231 1237
128. T. Paus, N. Otaky, Z. Caramanos, D. MacDonald, A. Zijdenbos, D. D'Avirro, D. Gutmans, C. Holmes, F. Tomaiuolo, and A.C. Evans In vivo morphometry of the intrasulcal gray matter in the human cingulate, paracingulate, and superior-rostral sulci: hemispheric asymmetries, gender differences and probability maps J. Comp. Neurol. 376 4 1996 664 673
129. K. Peremans, K. Audenaert, P. Blanckaert, F. Jacobs, F. Coopman, F. Verschooten, H. Van Bree, C. Van Heeringen, J. Mertens, and G. Slegers Effects of aging on brain perfusion and serotonin-2A receptor binding in the normal canine brain measured with single photon emission tomography Prog. Neuropsychopharmacol. Biol. Psychiatry 26 7-8 2002 1393 1404
130. E.K. Perry, G. Blessed, B.E. Tomlinson, R.H. Perry, T.J. Crow, A.J. Cross, G.J. Dockray, R. Dimaline, and A. Arregui Neurochemical activities in human temporal lobe related to aging and Alzheimer-type changes Neurobiol. Aging 2 4 1981 251 256
131. A. Pfefferbaum, D.H. Mathalon, E.V. Sullivan, J.M. Rawles, R.B. Zipursky, and K.O. Lim A quantitative magnetic resonance imaging study of changes in brain morphology from infancy to late adulthood Arch. Neurol. 51 9 1994 874 887
132. C.J. Pike Testosterone attenuates beta-amyloid toxicity in cultured hippocampal neurons Brain Res. 919 1 2001 160 165
133. I. Podreka, C. Baumgartner, E. Suess, C. Muller, T. Brucke, W. Lang, F. Holzner, M. Steiner, and L. Deecke Quantification of regional cerebral blood flow with IMP-SPECT. Reproducibility and clinical relevance of flow values Stroke 20 2 1989 183 191
134. K.E. Prothero, J.M. Stahl, and L. Carrel Dosage compensation and gene expression on the mammalian X chromosome: one plus one does not always equal two Chromosome Res. 17 5 2009 637 648
135. J. Putaala, A.J. Metso, T.M. Metso, N. Konkola, Y. Kraemer, E. Haapaniemi, M. Kaste, and T. Tatlisumak Analysis of 1008 consecutive patients aged 15 to 49 with first-ever ischemic stroke: the Helsinki young stroke registry Stroke 40 4 2009 1195 1203
136. T. Rabinowicz, D.E. Dean, J.M. Petetot, and G.M. de Courten-Myers Gender differences in the human cerebral cortex: more neurons in males; more processes in females J. Child Neurol. 14 2 1999 98 107
137. S.W. Rau, D.B. Dubal, M. Bottner, L.M. Gerhold, and P.M. Wise Estradiol attenuates programmed cell death after stroke-like injury J. Neurosci. 23 36 2003 11420 11426
138. N. Raz Aging of the brain and its impact on cognitive performance: integration of structural and functional findings F.I.M. Craik, T.A. Salthouse, Handbook of Aging and Cognition 2000 Erlbaum Mahwah, NJ
139. A. Razmara, D.N. Krause, and S.P. Duckles Testosterone augments endotoxin-mediated cerebrovascular inflammation in male rats Am. J. Physiol. Heart Circ. Physiol. 289 5 2005 H1843 H1850
140. E.M. Reiman, S.M. Armstrong, K.S. Matt, and J.H. Mattox The application of positron emission tomography to the study of the normal menstrual cycle Hum. Reprod. 11 12 1996 2799 2805
141. J. Ren Influence of gender on oxidative stress, lipid peroxidation, protein damage and apoptosis in hearts and brains from spontaneously hypertensive rats Clin. Exp. Pharmacol. Physiol. 34 5-6 2007 432 438
142. S. Renolleau, S. Fau, C. Goyenvalle, L.M. Joly, D. Chauvier, E. Jacotot, J. Mariani, and C. Charriaut-Marlangue Specific caspase inhibitor Q-VD-OPh prevents neonatal stroke in P7 rat: a role for gender J. Neurochem. 100 4 2007 1062 1071
143. S.M. Resnick, A.F. Goldszal, C. Davatzikos, S. Golski, M.A. Kraut, E.J. Metter, R.N. Bryan, and A.B. Zonderman One-year age changes in MRI brain volumes in older adults Cereb. Cortex 10 5 2000 464 472
144. P. Riccardi, D. Zald, R. Li, S. Park, M.S. Ansari, B. Dawant, S. Anderson, N. Woodward, D. Schmidt, and R. Baldwin Sex differences in amphetamine-induced displacement of [(18)F]fallypride in striatal and extrastriatal regions: a PET study Am. J. Psychiatry 163 9 2006 1639 1641
145. R.M. Ritzel, L.A. Capozzi, and L.D. McCullough Sex, stroke, and inflammation: the potential for estrogen-mediated immunoprotection in stroke Horm. Behav. 2012 http://dx.doi.org/10.1016/j.yhbeh.2012.04.007
146. V.L. Roger, A.S. Go, D.M. Lloyd-Jones, E.J. Benjamin, J.D. Berry, W.B. Borden, D.M. Bravata, S. Dai, E.S. Ford, and C.S. Fox Heart disease and stroke statistics - 2012 update: a report from the American Heart Association Circulation 125 1 2011 e2 e220
147. V.L. Roger, A.S. Go, D.M. Lloyd-Jones, E.J. Benjamin, J.D. Berry, W.B. Borden, D.M. Bravata, S. Dai, E.S. Ford, and C.S. Fox Heart disease and stroke statistics - 2012 update: a report from the American Heart Association Circulation 125 1 2012 e2 e220
148. J.I. Rojas, M.C. Zurru, M. Romano, L. Patrucco, and E. Cristiano Acute ischemic stroke and transient ischemic attack in the very old - risk factor profile and stroke subtype between patients older than 80 years and patients aged less than 80 years Eur. J. Neurol. 14 8 2007 895 899
149. J. Roquer, A.R. Campello, and M. Gomis Sex differences in first-ever acute stroke Stroke 34 7 2003 1581 1585
150. W. Rosamond, K. Flegal, K. Furie, A. Go, K. Greenlund, N. Haase, S.M. Hailpern, M. Ho, V. Howard, and B. Kissela Heart disease and stroke statistics - 2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee Circulation 117 4 2008 e25 e146
151. C.L. Rosen, V.A. Dinapoli, T. Nagamine, and T. Crocco Influence of age on stroke outcome following transient focal ischemia J. Neurosurg. 103 4 2005 687 694
152. J.E. Rossouw, G.L. Anderson, R.L. Prentice, A.Z. LaCroix, C. Kooperberg, M.L. Stefanick, R.D. Jackson, S.A. Beresford, B.V. Howard, and K.C. Johnson Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial JAMA 288 3 2002 321 333
153. G. Sanacora, G.F. Mason, D.L. Rothman, K.L. Behar, F. Hyder, O.A. Petroff, R.M. Berman, D.S. Charney, and J.H. Krystal Reduced cortical gamma-aminobutyric acid levels in depressed patients determined by proton magnetic resonance spectroscopy Arch. Gen. Psychiatry 56 11 1999 1043 1047
154. E. Schroeder, S. Vogelgesang, A. Popa-Wagner, and C. Kessler Neurofilament expression in the rat brain after cerebral infarction: effect of age Neurobiol. Aging 24 1 2003 135 145
155. J.F. Seymour, B. Pro, L.M. Fuller, J.T. Manning, F.B. Hagemeister, J. Romaguera, M.A. Rodriguez, C.S. Ha, T.L. Smith, and A. Ayala Long-term follow-up of a prospective study of combined modality therapy for stage I-II indolent non-Hodgkin's lymphoma J. Clin. Oncol. 21 11 2003 2115 2122
156. S. Shapira, M. Sapir, A. Wengier, E. Grauer, and T. Kadar Aging has a complex effect on a rat model of ischemic stroke Brain Res. 925 2 2002 148 158
157. B.B. Sherwin The critical period hypothesis: can it explain discrepancies in the oestrogen-cognition literature? J. Neuroendocrinol. 19 2 2007 77 81
158. M.W. Sieber, R.A. Claus, O.W. Witte, and C. Frahm Attenuated inflammatory response in aged mice brains following stroke PLoS ONE 6 10 2011 e26288
159. J.W. Simpkins, S.H. Yang, Y. Wen, and M. Singh Estrogens, progestins, menopause and neurodegeneration: basic and clinical studies Cell. Mol. Life Sci. 62 3 2005 271 280
160. N. Sinha, N.Z. Baquer, and D. Sharma Anti-lipidperoxidative role of exogenous dehydroepiendrosterone (DHEA) administration in normal ageing rat brain Indian J. Exp. Biol. 43 5 2005 420 424
161. D.O. Slosman, C. Chicherio, C. Ludwig, L. Genton, S. de Ribaupierre, D. Hans, C. Pichard, E. Mayer, J.M. Annoni, and A. de Ribaupierre (133)Xe SPECT cerebral blood flow study in a healthy population: determination of T-scores J. Nucl. Med. 42 6 2001 864 870
162. Y.R. Smith, J.K. Zubieta, M.G. del Carmen, R.F. Dannals, H.T. Ravert, H.A. Zacur, and J.J. Frost Brain opioid receptor measurements by positron emission tomography in normal cycling women: relationship to luteinizing hormone pulsatility and gonadal steroid hormones J. Clin. Endocrinol. Metab. 83 12 1998 4498 4505
163. Y.R. Smith, S. Minoshima, D.E. Kuhl, and J.K. Zubieta Effects of long-term hormone therapy on cholinergic synaptic concentrations in healthy postmenopausal women J. Clin. Endocrinol. Metab. 86 2 2001 679 684
164. R.D. Smrt, R.L. Pfeiffer, and X. Zhao Age-dependent expression of MeCP2 in a heterozygous mosaic mouse model Hum. Mol. Genet. 20 9 2011 1834 1843
165. R. Soares, S. Guo, J. Russo, and F. Schmitt Role of the estrogen antagonist ICI 182,780 in vessel assembly and apoptosis of endothelial cells Ultrastruct. Pathol. 27 1 2003 33 39
166. V. Solfrizzi, A.M. Colacicco, A. D'Introno, C. Capurso, A.D. Parigi, S.A. Capurso, F. Torres, A. Capurso, and F. Panza Macronutrients, aluminium from drinking water and foods, and other metals in cognitive decline and dementia J. Alzheimers Dis. 10 2-3 2006 303 330
167. K. Spengos, and K.N. Vemmos Female predominance at very young ages and other similarities between Finnish and Greek young ischemic stroke patients Stroke 40 7 2009 e491 author reply e492
168. Z. Spolarics The X-files of inflammation: cellular mosaicism of X-linked polymorphic genes and the female advantage in the host response to injury and infection Shock 27 6 2007 597 604
169. C. Stehlik, R. de Martin, I. Kumabashiri, J.A. Schmid, B.R. Binder, and J. Lipp Nuclear factor (NF)-kappaB-regulated X-chromosome-linked iap gene expression protects endothelial cells from tumor necrosis factor alpha-induced apoptosis J. Exp. Med. 188 1 1998 211 216
170. R.H. Straub The complex role of estrogens in inflammation Endocr. Rev. 28 5 2007 521 574
171. L. Sunday, C. Osuna, D.N. Krause, and S.P. Duckles Age alters cerebrovascular inflammation and effects of estrogen Am. J. Physiol. Heart Circ. Physiol. 292 5 2007 H2333 H2340
172. G.R. Sutherland, G.A. Dix, and R.N. Auer Effect of age in rodent models of focal forebrain ischemia Stroke 27 9 1996 1663 1667 Discussion: 1668
173. S. Suzuki, C.M. Brown, C.D. Dela Cruz, E. Yang, D.A. Bridwell, and P.M. Wise Timing of estrogen therapy after ovariectomy dictates the efficacy of its neuroprotective and antiinflammatory actions Proc. Natl. Acad. Sci. USA 104 14 2007 6013 6018
174. S. Suzuki, C.M. Brown, and P.M. Wise Neuroprotective effects of estrogens following ischemic stroke Front. Neuroendocrinol. 30 2 2009 201 211
175. D.F. Swaab, and E. Fliers A sexually dimorphic nucleus in the human brain Science 228 4703 1985 1112 1115
176. Z. Talebizadeh, S.D. Simon, and M.G. Butler X chromosome gene expression in human tissues: male and female comparisons Genomics 88 6 2006 675 681
177. Z. Tan, X. Li, K.A. Kelly, C.L. Rosen, and J.D. Huber 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. 1281 2009 84 90
178. G. Tang, Y. Minemoto, B. Dibling, N.H. Purcell, Z. Li, M. Karin, and A. Lin Inhibition of JNK activation through NF-kappaB target genes Nature 414 6861 2001 313 317
179. X.K. Tong, C. Lecrux, and E. Hamel Age-dependent rescue by simvastatin of Alzheimer's disease cerebrovascular and memory deficits J. Neurosci. 32 14 2012 4705 4715
180. A. Towfighi, J.L. Saver, R. Engelhardt, and B. Ovbiagele A midlife stroke surge among women in the United States Neurology 69 20 2007 1898 1904
181. A. Towfighi, D. Markovic, and B. Ovbiagele Persistent sex disparity in midlife stroke prevalence in the United States Cerebrovasc. Dis. 31 4 2011 322 328
182. B.B. Turner, and D.A. Weaver Sexual dimorphism of glucocorticoid binding in rat brain Brain Res. 343 1 1985 16 23
183. L.C. Turtzo, and L.D. McCullough Sex-specific responses to stroke Future Neurol. 5 1 2010 47 59
184. L.C. Turtzo, C. Siegel, and L.D. McCullough X chromosome dosage and the response to cerebral ischemia J. Neurosci. 31 37 2011 13255 13259
185. S.J. Vannucci, and P.D. Hurn Gender differences in pediatric stroke: is elevated testosterone a risk factor for boys? Ann. Neurol. 66 6 2009 713 714
186. E. Vegeto, S. Ghisletti, C. Meda, S. Etteri, S. Belcredito, and A. Maggi Regulation of the lipopolysaccharide signal transduction pathway by 17beta-estradiol in macrophage cells J. Steroid Biochem. Mol. Biol. 91 1-2 2004 59 66
187. C.M. Viscoli, L.M. Brass, W.N. Kernan, P.M. Sarrel, S. Suissa, and R.I. Horwitz A clinical trial of estrogen-replacement therapy after ischemic stroke N. Engl. J. Med. 345 17 2001 1243 1249
188. R.Y. Wang, P.S. Wang, and Y.R. Yang Effect of age in rats following middle cerebral artery occlusion Gerontology 49 1 2003 27 32
189. R.Y. Wang, S.M. Yu, and Y.R. Yang Treadmill training effects in different age groups following middle cerebral artery occlusion in rats Gerontology 51 3 2005 161 165
190. Q. Wang, X.N. Tang, and M.A. Yenari The inflammatory response in stroke J. Neuroimmunol. 184 1-2 2007 53 68
191. J.M. Wang, X. Hou, S. Adeosun, R. Hill, S. Henry, I. Paul, R.W. Irwin, X.M. Ou, S. Bigler, and C. Stockmeier A dominant negative ERbeta splice variant determines the effectiveness of early or late estrogen therapy after ovariectomy in rats PLoS ONE 7 3 2012 e33493
192. S.F. Witelson Hand and sex differences in the isthmus and genu of the human corpus callosum. A postmortem morphological study Brain 112 Pt. 3 1989 799 835
193. S.F. Witelson, I.I. Glezer, and D.L. Kigar Women have greater density of neurons in posterior temporal cortex J. Neurosci. 15 5 Pt 1 1995 3418 3428
194. S.J. Won, L. Xie, S.H. Kim, H. Tang, Y. Wang, X. Mao, S. Banwait, and K. Jin Influence of age on the response to fibroblast growth factor-2 treatment in a rat model of stroke Brain Res. 1123 1 2006 237 244
195. D.F. Wong, E.P. Broussolle, G. Wand, V. Villemagne, R.F. Dannals, J.M. Links, H.A. Zacur, J. Harris, S. Naidu, and C. Braestrup In vivo measurement of dopamine receptors in human brain by positron emission tomography. Age and sex differences Ann. N.Y. Acad. Sci. 515 1988 203 214
196. S.M. Wuerzberger-Davis, Y. Nakamura, B.J. Seufzer, and S. Miyamoto NF-kappaB activation by combinations of NEMO SUMOylation and ATM activation stresses in the absence of DNA damage Oncogene 26 5 2007 641 651
197. J. Xu, and C.M. Disteche Sex differences in brain expression of X- and Y-linked genes Brain Res. 1126 1 2006 50 55
198. B.B. Yeap, Z. Hyde, O.P. Almeida, P.E. Norman, S.A. Chubb, K. Jamrozik, L. Flicker, and G.J. Hankey Lower testosterone levels predict incident stroke and transient ischemic attack in older men J. Clin. Endocrinol. Metab. 94 7 2009 2353 2359
199. T. Yoshida, Y. Kuwabara, M. Sasaki, T. Fukumura, A. Ichimiya, M. Takita, K. Ogomori, Y. Ichiya, and K. Masuda Sex-related differences in the muscarinic acetylcholinergic receptor in the healthy human brain - a positron emission tomography study Ann. Nucl. Med. 14 2 2000 97 101
200. M. Yuan, C. Siegel, Z. Zeng, J. Li, F. Liu, and L.D. McCullough Sex differences in the response to activation of the poly (ADP-ribose) polymerase pathway after experimental stroke Exp. Neurol. 217 1 2009 210 218
201. X. Zhao, and M. Eghbali-Webb Gender-related differences in basal and hypoxia-induced activation of signal transduction pathways controlling cell cycle progression and apoptosis, in cardiac fibroblasts Endocrine 18 2 2002 137 145
202. J.N. Zhou, M.A. Hofman, L.J. Gooren, and D.F. Swaab A sex difference in the human brain and its relation to transsexuality Nature 378 6552 1995 68 70
203. J.K. Zubieta, R.F. Dannals, and J.J. Frost Gender and age influences on human brain mu-opioid receptor binding measured by PET Am. J. Psychiatry 156 6 1999 842 848