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Updated: Sep 25, 2025
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Published on: June 20, 2025
Sex Differences in Poststroke Inflammation: a Focus on Microglia Across the Lifespan
Irene F Ugidos1,2, Cristiana Pistono1, Paula Korhonen1
1A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio (I.F.U., C.P., P.K., M.G.-B., V.S., P.K., I.S., J.J., T.M.).
Abstract:
Stroke is one of the leading causes of death worldwide and currently only few therapeutic options are available. Stroke is a sexually dimorphic disease contributing to the difficulty in finding efficient treatments. Poststroke neuroinflammation is geared largely by brain microglia and infiltrating peripheral immune cells and largely contributes to sex differences in the outcome of stroke. Microglia, since very early in the development, are sexually divergent, imprinting specific sex-related features. The diversity in terms of microglial density, morphology, and transcriptomic and proteomic profiles between sexes remains in the adulthood and is likely to contribute to the observed sex-differences on the postischemic inflammation. The impact of sexual hormones is fundamental: changes in terms of risk and severity have been observed for females before and after menopause underlining the importance of altered circulating sexual hormones. Moreover, aging is a driving force for changes that interact with sex, shifting the inflammatory response in a sex-dependent manner. This review summarizes the present literature on sex differences in stroke-induced inflammatory responses, with the focus on different microglial responses along lifespan.
Insights
Stroke impacts men and women differently due to sex-based variations in brain immune cells called microglia. Understanding these sex differences is crucial for developing effective stroke treatments.
Area of Science:
- Neuroscience
- Immunology
- Sex Differences in Disease
Background:
- Stroke is a leading global cause of death with limited therapeutic options.
- Stroke is a sexually dimorphic disease, complicating treatment development.
- Neuroinflammation, driven by microglia and immune cells, significantly impacts stroke outcomes and exhibits sex-based variations.
Purpose of the Study:
- To review current literature on sex differences in stroke-induced inflammatory responses.
- To focus on the lifespan-dependent variations in microglial responses to stroke.
- To highlight the role of microglia in sex-specific post-stroke inflammation.
Main Methods:
- Literature review of studies investigating sex differences in stroke.
- Analysis of research on microglial biology and function across the lifespan.
- Examination of the influence of sex hormones and aging on neuroinflammation post-stroke.
Main Results:
- Microglia exhibit sexually divergent characteristics from early development through adulthood.
- Sex differences in microglial density, morphology, and molecular profiles contribute to varied inflammatory responses.
- Sexual hormones and aging interact to modulate inflammatory responses in a sex-dependent manner.
Conclusions:
- Sex differences in microglial responses are a critical factor in stroke outcomes.
- Understanding these sex-based inflammatory variations is essential for advancing stroke therapy.
- Targeting sex-specific inflammatory pathways holds potential for improved stroke treatment.
