Exercise Preconditioning Regulates the Toll-Like Receptor 4/Nuclear Factor-κB Signaling Pathway and Reduces Cerebral Ischemia/Reperfusion Inflammatory Injury: A Study in Rats

Objective: To explore the influence of exercise preconditioning (EP) on the activity of the toll-like receptor (TLR)4/nuclear factor (NF)-kappa B signaling pathway in a rat model of cerebral ischemia/reperfusion (I/R) inflammatory injury. Methods: Ischemia was induced in rats using transient middle cerebral artery occlusion (tMCAO) after 3 weeks of EP. Fifty-four rats were divided into sham, MCAO, and 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-kappa B were analyzed. In addition, enzyme-linked immunosorbent assays were used to detect the levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta in peripheral serum. Results: Twenty-four hours after cerebral I/R injury, the neurological deficit scores decreased and ischemic cortical damage alleviated in EP+MCAO group; the number of TLR4- and NF-kappa B-positive cells, the expression of TLR4 and NF-kappa B in the ischemic side, and the concentrations of TNF-alpha and IL-1 beta in the peripheral serum were lower in EP+MCAO group than those in the MCAO group (P<.05). Conclusions: 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-kappa B signaling pathway and the inhibition of central and peripheral inflammatory cascades during cerebral I/R injury.