Ecotoxicology and Environmental Safety · Oct 11, 2025

Exercise protects against PM2.5 exacerbated cerebral ischemia/reperfusion injury via the gut-brain axis in mice

By Sun S, Qin M, Cao Q et al.

Fine particulate matter (PM2.5) is a harmful environmental pollutant that affects ischemic stroke. Exercise has been shown to protect against post-stroke cognitive impairment (PSCI) partly through the gut-brain axis. However, the gut-brain axis mechanisms underlying PM2.5-induced PSCI, as well as the modulatory role of exercise, remain poorly understood. In this study, C57BL/6 J mice underwent different exercise regimens prior to PM2.5 exposure (5.45 mg/kg body weight). Results indicated that PM2.5 exposure caused disruption of the intestinal epithelial barrier and triggered inflammatory responses. This was accompanied by reduced levels of tight junction proteins (ZO-1, Occludin, and Claudin-5) and increased expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). Moreover, the inflammatory response further impaired blood-brain barrier (BBB) integrity, exacerbating cerebral ischemia/reperfusion (I/R) injury and impairing cognitive function. 16S rDNA sequencing of gut microbiota revealed that PM2.5 disrupted intestinal microbial balance, reducing beneficial genera such as Lactobacillus and Streptococcus, while increasing potentially harmful taxa, including Desulfobacterota, Verrucomicrobia, and Hydrogenophaga. Importantly, exercise markedly attenuated PM2.5-induced PSCI via the gut-brain axis, with the strongest protective effect observed after 6 weeks of exercise. These findings provide a mechanistic basis for understanding how exercise attenuates PM2.5-induced PSCI.

doi.org/10.1016/j.ecoenv.2025.119202Open accessPubMed 41076862Interventions