X chromosome dosage and the response to cerebral ischemia

Abstract

Gonadal hormones contributetoischemic neuroprotection, but cannotfullyexplaintheobservedsexual dimorphisminstroke outcomes seen during life stages with low sex steroid hormones. Sex chromosomal complement (XX in females; XY in males) may also contribute to ischemic sexual dimorphism. A transient middle cerebral artery occlusion model was used to investigate the role of X chromosome dosage in female XX and XO littermates of two mouse strains (Paf and Eda Ta). Cohorts of XX and XO gonadally intact, ovariectomized, and ovariectomized females supplemented with estrogen were examined. Infarct sizes were equivalent between ovariectomized XX and XO mice, between intactXX and XOmice, and between estrogen-supplemented ovariectomized XXand XO mice. This is the first study to investigate the role of sex chromosome dosagein the response to cerebralischemia. Neither the number of Xchromosomesnor the parent of origin of the remaining X chromosome had a significant effect on the degree of cerebral infarction after experimental stroke in adult female mice. Estrogen was protective against cerebral ischemia in both XX and XO mice. © 2011 the authors.