MiR-21-5p/RasGRP1 Axis Mediates Exercise Preconditioning-Induced Microvascular Remodeling After Cerebral Ischemia-Reperfusion in Rats [miRNA-seq]

ABSTRACT: Regular exercise before stroke has been associated with reduced neurological injury after ischemic stroke; however, its effects on microvascular remodeling in the ischemic penumbra and the underlying molecular mechanisms remain incompletely understood. In this study, a rat middle cerebral artery occlusion/reperfusion (MCAO/R) model was established. Rats underwent 3 weeks of moderate-intensity aerobic exercise preconditioning, and its effects on neurological deficits, cerebral infarct volume, TUNEL-positive cell death, and microvascular remodeling after cerebral ischemia/reperfusion injury (CIRI) were evaluated. The underlying mechanisms were investigated using integrated transcriptomic analysis and targeted molecular validation. Exercise preconditioning alleviated neurological deficits, reduced cerebral infarct volume and TUNEL-positive cell death, increased CD31-positive vascular coverage and vascular length, and enhanced the expression of endothelial junction-associated proteins, including ZO-1 and VE-cadherin. Integrated miRNA-mRNA transcriptomic analysis identified the miR-21-5p/RasGRP1/Ras/ERK signaling axis as a candidate pathway underlying the neurovascular protective effects of exercise preconditioning. Further validation demonstrated that exercise preconditioning reduced miR-21-5p expression, increased RasGRP1 expression, and enhanced Ras/ERK signaling activity. Conversely, miR-21-5p overexpression or RasGRP1 knockdown attenuated the beneficial effects of exercise preconditioning on neurological deficits, tissue injury, and microvascular remodeling. These findings suggest that exercise preconditioning promotes early neurovascular protection after CIRI, at least partly through modulation of the miR-21-5p/RasGRP1/Ras/ERK signaling axis, providing new insights into exercise-mediated stroke protection and potential therapeutic targets.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE345906 | GEO | 2026/09/07

REPOSITORIES: GEO