Exercise preconditioning (EP) induces ischemic tolerance and reduces inflammatory injury; however, the mechanism underlying these effects remains unclear. In this study, the influence of EP on the activity of the toll-like receptor (TLR) 4/nuclear factor (NF)-κB-signaling pathway was explored in a rat model of cerebral ischemia/reperfusion (I/R) inflammatory injury.

Ischemia was induced in rats using transient middle cerebral artery occlusion (tMCAO) after 3 weeks of EP. Male SD rats (n=54) were divided into sham, MCAO, and EP (EP+MCAO) groups. Following the induction of cerebral I/R injury, rats were scored for neurological deficits. Various techniques were used to evaluate ischemic infarct volume and explore pathological changes in tissue morphology after cerebral I/R injury, wherein the levels of TLR4 and NF-κB were analyzed. In addition, enzyme-linked immunosorbent assays were used to detect the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in peripheral serum.

Twenty-four hours after cerebral I/R injury, the neurological deficit scores of animals in the EP+MCAO group were significantly lower than those in the MCAO group (P<0.05). A significant reduction in cerebral infarct volume was also observed (P<0.05). Pathological analysis demonstrated that ischemic cortical damage was alleviated in the EP+MCAO group, and the number of TLR4- and NF-κB-positive cells decreased in the infarct region (P<0.05). TLR4 and NF-κB expression was downregulated in the ischemic side (P<0.05), and the concentrations of TNF-α and IL-1β were significantly reduced in the peripheral serum (P<0.05).

The present study indicates that EP can improve cerebral I/R-induced neurological deficits in rats, reduce infarct volume, mitigate pathological damage in the ischemic cortex, and exert neuroprotective effects. The mechanism underlying these effects might involve the regulation of the TLR4/NF-κB signaling pathway and the inhibition of central and peripheral inflammatory cascades during cerebral I/R injury.