A systematic review identified only two studies evaluating sex-specific metabolic responses to acute ischemic stroke and functional outcomes, highlighting a critical gap in stroke research.
Systematic Review
Does biological sex influence the metabolic response and neurological outcomes in acute ischemic stroke?
There is a critical lack of data evaluating sex as a biological variable in the metabolic response to acute ischemic stroke, though limited evidence suggests sex-specific differences in amino acid and energy metabolism that may influence neurological outcomes.
Women continue to face a greater lifetime morbidity and mortality from stroke and have been shown to respond differently to stroke treatments compared to men. Since 2016, updated National Institutes of Health (NIH) policies require research studies to consider sex as a biological variable. However, the way in which this policy affects study design, analysis, and reporting is variable, with few studies performing and reporting a subgroup analysis based on biological sex. In acute ischemic stroke, the underlying biological explanation for sex-based differences in patient outcomes and response to treatments remains understudied. We performed a systematic review of preclinical and clinical research studies that explored sex differences in the metabolic response to acute ischemic stroke as it relates to neurological outcomes. Through a literature search in Ovid Medline, Embase, and Web of Science, 1,004 potential references were identified for screening. After abstract and full-text review, we identified only two studies which assessed metabolic response to acute ischemic stroke (within 72 h of last known well) and neurological outcome Barthel Index, modified Rankin Scale (mRS) or an equivalent in preclinical models and reported results based on biological sex. One article was a preclinical rat model and the other a clinical cohort study. In both studies, metabolites involved in amino acid metabolism, energy metabolism, fat metabolism, or oxidative stress were identified. We review these results and link to additional articles that use metabolomics to identify metabolites differentially expressed by sex or regulated based on stroke outcomes, but not both. The results of this systematic review should not only help identify targets in need of further investigation to improve the understanding of sex differences in the pathophysiology of acute ischemic stroke, but also highlight the critical need to expand the incorporation of sex as a biological variable in acute stroke research beyond simply including both sexes and reporting the proportion of males/females in each population studied.
Dylla et al. (Thu,) conducted a systematic review in Acute ischemic stroke. Sex-specific metabolic response was evaluated on Metabolic response to acute ischemic stroke and neurological outcome based on biological sex. A systematic review identified only two studies evaluating sex-specific metabolic responses to acute ischemic stroke and functional outcomes, highlighting a critical gap in stroke research.