Ischemic Stroke Pathology and Gender Factors

Ischemic stroke arises from an interruption of cerebral blood flow, typically due to arterial occlusion, resulting in rapid depletion of oxygen and glucose in affected brain regions. The ensuing cascade involves excitotoxic neuronal injury, disruption of the blood–brain barrier, oxidative stress and recruitment of innate immune cells, notably microglia and peripheral macrophages. As the infarct evolves, pro-inflammatory cytokines exacerbate tissue damage, while later stages engage reparative processes including angiogenesis and remodelling of neural networks. A growing body of research highlights pronounced sexual dimorphism in both incidence and outcome. Premenopausal women benefit from oestrogen-mediated vasodilation, antioxidant effects and modulation of immune cell phenotypes, whereas post-menopausal decline in gonadal hormones correlates with increased stroke severity and poorer recovery. Beyond hormonal influences, sex chromosome complement contributes to differential gene expression and epigenetic regulation of inflammatory pathways. Together, these factors underpin sex-specific vulnerabilities and responses to therapy, indicating that precision treatment for ischemic stroke should account for both biological sex and hormonal status.

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Ischemic Stroke Pathology and Gender Factors publication trend

The graph below shows the total number of articles in ischemic stroke pathology and gender factors across all publications each year (not limited to Nature Index journals).

Technical terms

Ischemic stroke: Brain injury caused by obstruction of blood flow, leading to tissue infarction.

Neuroinflammation: Activation of central and peripheral immune cells in the brain, driving secondary injury after stroke.

Microglia: Resident immune cells of the central nervous system that adopt pro- or anti-inflammatory phenotypes.

17β-Estradiol: The primary form of oestrogen in premenopausal females, with vasodilatory and immunomodulatory actions.

X chromosome inactivation (XCI): Epigenetic silencing of one X chromosome in females, with some genes “escaping” silencing to influence sex differences.

References

1. Estradiol mediates colonic epithelial protection in aged mice after stroke and is associated with shifts in the gut microbiome. Gut Microbes (2023).
2. Immunomodulatory role of estrogen in ischemic stroke: neuroinflammation and effect of sex. Frontiers in Immunology (2023).
3. Stroke sensitivity in the aged: sex chromosome complement vs. gonadal hormones. Aging (2016).
4. Post-ischemic estradiol treatment reduced glial response and triggers distinct cortical and hippocampal signaling in a rat model of cerebral ischemia. Journal of Neuroinflammation (2012).
5. X chromosome escapee genes are involved in ischemic sexual dimorphism through epigenetic modification of inflammatory signals. Journal of Neuroinflammation (2021).