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Abstract

This study investigates the effects of age, sex, and diabetes on transcriptome and proteome changes in the brain following cerebral ischemia. Utilizing a multidimensional approach, we integrate transcriptomic and proteomic analyses to elucidate the complex molecular landscape underlying stroke pathophysiology. Age-related alterations in gene expression and protein profiles are characterized by dysregulated pathways associated with inflammation, oxidative stress, and neuronal repair mechanisms. Sex-specific responses reveal distinct molecular signatures implicated in neuroprotection, neuroinflammation, and synaptic remodeling post-ischemia. Moreover, diabetesinduced modifications in gene and protein expression highlight perturbations in glucose metabolism, oxidative stress, and vascular dysfunction, exacerbating cerebral ischemic damage. By comprehensively delineating the interplay between age, sex, and diabetes in shaping brain molecular responses to ischemia, this study provides critical insights for personalized stroke management and targeted therapeutic interventions.