Treadmill exercise decreases cerebral edema in rats with local cerebral infarction by modulating AQP4 polar expression through the caveolin-1/TRPV4 signaling pathway

Rehabilitation therapy is beneficial for patients with ischemic stroke. Our previous study showed that treadmill training is conducive to neurological function in rats that underwent middle cerebral artery occlusion (MCAO). However, whether exercise benefits cerebral edema and the underlying mechanism remain unclear. This study investigated the influence of treadmill exercise on brain edema and the mechanism of its formation and elimination. The MCAO model was established with Sprague-Dawley (SD) rats, and lentivirus-mediated caveolin-1 shRNA was used to investigate the role of caveolin-1 in brain edema. As expected, we found that treadmill exercise has a beneficial effect on brain edema after stroke. Training led to a significant increase in the expression of caveolin-1 and TRPV4; and reduced brain water content and blood-brain barrier (BBB) damage. This treatment also changed the localization of aquaporin-4 (AQP4). Moreover, the effect of treadmill training on the polar expression of AQP4 differed over time. The results showed that early treadmill training inhibited the polar expression of AQP4, and later promoted its expression. However, the rats that were injected with the caveolin-1 shRNA lentivirus exhibited enhanced edema. Caveolin-1 shRNA eliminated the protective effect induced by exercise, which is consistent with the downregulation of TRPV4 expression. The findings indicate that treadmill training improves brain edema through the caveolin-1/TRPV4/AQP4 pathway.