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. Author manuscript; available in PMC: 2010 Nov 1.
Published in final edited form as: Steroids. 2009 Nov 10;75(11):754–759. doi: 10.1016/j.steroids.2009.10.014

Table 1.

Sex-specific cell death mechanisms in ischemic brain injury.

Cell/species Insult/mechanism tested Sex difference References
Dopaminergic neurons High concentrations dopamine Female cells have greater survival vs. male [21]
Cortical plate neurons; ventricular zone neurons Longevity in culture, expression of protective kinases Female cells survive longer, respond to injury with higher kinase expression [22]
Primary neuronal culture Neurotoxins, including glutamate, ONOO, H2O2, staurosporine Higher sensitivity in males to glutamate-ONOO injury; females are more sensitive to apopototic challenges [23]
Cortical astrocytes OGD with or without inflammatory stimulus (TNFα; IL1β); role of P450 aromatase Greater survival of female cells after OGD, higher aromatase expression, higher ability to synthesize cytoprotective estradiol [24,25]
Cultured hippocampal slice OGD, NMDA exposure; NO toxicity Less injury in females slices; only male slices received benefit from nNOS inhibition [26]
Intact male vs. female mouse brain Focal cerebral ischemia; role of nNOS, PARP Male but not female brain is protected by genetic loss or pharmacological inhibitors of nNOS, PARP and downstream mechanisms [14]
Intact male vs. female mouse brain Focal cerebral ischemia; role of apoptotic mediators PAR formation and AIF nuclear translocation occurs in both sexes, but resulting apoptotic damage only in males [33]
Intact neonatal male vs. female mouse brain Hypoxia–ischemia; role of PARP Male but not female brain is protected by genetic loss of PARP [29]
Intact neonatal male vs. female mouse brain Moderate but not severe hypoxia–ischemia; role of AIF and caspase activation More pronounced AIF nuclear translocation in male brain; caspase activation greater in female brain [30]
Intact male vs. female mouse brain Focal cerebral ischemia; role of iNOS Male but not female brain is protected by genetic loss or pharmacological inhibition of iNOS [35]
Intact neonatal male vs. female rat brain Focal cerebral ischemia; role of caspase activation Female but not male brain was protected by pharmacological broad spectrum, caspase inhibition [31]
Young and aged male vs. female intact mouse brain Focal cerebral ischemia; role of cytochrome C release and caspase activation Earlier cytochrome C release in female vs. male brain; female brain but not male brain was protected by pharmacological broad spectrum, caspase inhibition [32]
Intact male vs. female mouse brain, expressing transgenic luciferase gene, GFAP promoter Focal cerebral ischemia; role of astrocyte activation Early brain inflammation as measured by GFAP intensity is higher in female vs. male; unlike male, GFAP intensity does not correlate with tissue damage in female [37]

Abbreviations—AIF: apoptosis-inducing factor; GFAP: glial fibrillary protein; H2O2 hydrogen peroxide; iNOS: inducible isoform nitric oxide synthase; IL1β: interleukin 1-β; nNOS: neuronal isoform nitric oxide synthase; NMDA: N-methyl-d-aspartic acid; OGD: oxygen-glucose deprivation; ONOO: peroxynitrate; PAR: poly-ADP-ribose; PARP: poly-ADP-ribose polymerase; TNFα: tumor necrosis factor α.