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Prog Neurobiol. 2019 May;176:73-85. doi: 10.1016/j.pneurobio.2018.08.001. Epub 2018 Aug 16.

Elucidating sex differences in response to cerebral ischemia: immunoregulatory mechanisms and the role of microRNAs.

Author information

1
Stanford University School of Medicine, Department of Anesthesiology, Perioperative & Pain Medicine, United States; Stanford University School of Medicine, Department of Ophthalmology, United States.
2
Stanford University School of Medicine, Department of Anesthesiology, Perioperative & Pain Medicine, United States.
3
Stanford University School of Medicine, Department of Anesthesiology, Perioperative & Pain Medicine, United States. Electronic address: cstary@stanford.edu.

Abstract

Cerebral ischemia remains a major cause of death and disability worldwide, yet therapeutic options remain limited. Differences in sex and age play an important role in the final outcome in response to cerebral ischemia in both experimental and clinical studies: males have a higher risk and worse outcome than females at younger ages and this trend reverses in older ages. Although the molecular mechanisms underlying sex dimorphism are complex and are still not well understood, studies suggest steroid hormones, sex chromosomes, differential cell death and immune pathways, and sex-specific microRNAs may contribute to the outcome following cerebral ischemia. This review focuses on differential effects between males and females on cell death and immunological pathways in response to cerebral ischemia, the central role of innate sex differences in steroid hormone signaling, and upstreamregulation of sexually dimorphic gene expression by microRNAs.

KEYWORDS:

Estrogen; Inflammation; Non-coding RNAs; Progesterone; Sex-differences; Stroke

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