Suppression of TLR4/NF-κB Signaling Pathway Improves Cerebral Ischemia–Reperfusion Injury in Rats

The present study aimed to investigate the effects of the toll-like receptor 4 (TLR4)/nuclear factor-kappaB (NF-ҡB) signaling pathway in cerebral ischemia–reperfusion injury. A total of 125 male Sprague Dawley (SD) rats were selected for this study. Fifty SD rats were randomly divided into the control, sham injury, 0.5 h perfusion, 2 h perfusion, and 6 h perfusion groups to establish the model of ischemia–reperfusion. The rat brain injury model was established using the other 75 male SD rats, and different model groups with different treatments were established (15 rats per group): model control group (injected with 10 μL of saline solution), model + TAK-242 group (injected with resatorvid), model + PDTC group (injected with pyrrolidine dithiocarbamate), model + LPS group (injected with lipopolysaccharide), and sham injury group (incision to the neck skin and injected with 10 μL of saline solution for normal rats). These five groups were further assigned into three subgroups: day 3 group, day 7 group, and day 21 group. To determine how the TLR4/NF-қB signal pathway affects cerebral ischemia–reperfusion injuries, various methods including the Morris water maze, triphenyl tetrazolium chloride (TTC) staining, hematoxylin–eosin (HE) staining, and western blotting were employed in this study. No neurological deficit was observed in rats from the model control and sham injury groups. A slight neurological deficit was found in the 0.5 h reperfusion group, while in the 2 and 6 h perfusion groups, neurological dysfunction was evident. Compared to the sham injury group, the model control group displayed a longer escape latency (EL) and increased cerebral infarction volume and pathological changes with enhanced expression of TLR4 and NF-κB (all P < 0.05). The inhibition of the TLR4/NF-κB signal pathway shortened rat EL and diminished cerebral infarction volume, and the pathological changes became less evident (all P < 0.05), while the activation of the TLR4/NF-κB signal pathway elongated rat EL, enlarged infarction volume, and increased cerebral pathological change (all P < 0.05). Pearson correlation analysis demonstrated that TLR4/NF-κB expression is correlated with the extent of rat brain damage. Cerebral ischemia–reperfusion injury in rats can be alleviated via the inhibition of the TLR4/NF-κB signaling pathway.