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

- Stroke risk and stroke outcomes are influenced by age and sex.
- Astrocytes play a key role in the brain's response to stroke.
- Sex differences in stroke severity may be related to gonadal hormones acting on/through astrocytes.
- The astrocytic response to ischemia is impaired with aging.
- Epigenetic alterations in astrocytes may underlie worsened outcomes during aging.

Ischemic stroke occurs more often among the elderly, and within this demographic, women are at an increased risk for stroke and have poorer functional recovery than men. This is also well replicated in animal studies where aging females are shown to have more extensive brain tissue loss as compared to adult females. Astrocytes provide nutrients for neurons, regulate glutamate levels, and release neurotrophins and thus play a key role in the events that occur following ischemia. In addition, astrocytes express receptors for gonadal hormones and synthesize several neurosteroids suggesting that the sex differences in stroke outcome may be mediated through astrocytes. This review discusses key astrocytic responses to ischemia including, reactive gliosis, excitotoxicity, and neuroinflammation. In light of the age and sex differences in stroke outcomes, this review highlights how aging and gonadal hormones influence these responses. Lastly, astrocyte specific changes in gene expression and epigenetic modifications during aging and following ischemia are discussed as possible molecular mechanisms for impaired astrocytic functioning.