Resveratrol attenuates pyroptosis and neuroinflammation by inhibiting the TLR4/NF-κB/AIM2 pathway in ischemic stroke rats

Neuroinflammation is an important factor affecting the prognosis of ischemic brain injury and has become a potential target for stroke treatment. Resveratrol is a natural product with multiple biological activities, including anti-neuroinflammatory, anti-oxidative stress, and anti-apoptotic effects. This study focuses on the mechanism by which resveratrol protects neurological function after stroke by inhibiting neuroinflammation. A rat model of ischemic stroke was established through middle cerebral artery occlusion (MCAO). Neurological function was assessed via 2,3,5-triphenyltetrazolium chloride (TTC) staining, neurological deficit scoring, and immunohistochemical analysis. Animal behaviors were evaluated using the elevated plus maze, open field test, social interaction test, and sucrose preference test. Neuroinflammation was examined by measuring the expression of inflammatory factors including IL-6, IL-1β, and TNF-α. Oxidative stress was assessed by detecting the levels of glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC). The expression of key proteins involved in neuroinflammation- and oxidative stress-related signaling pathways was examined by Western blotting. The results demonstrated that resveratrol effectively reduced neurological deficit scores, decreased cerebral infarct volume, and alleviated post-stroke cognitive impairment (PSCI) in rats. Additionally, resveratrol significantly suppressed neuroinflammation and improved antioxidant capacity. Further mechanistic investigations revealed that resveratrol markedly inhibited the TLR4/NF-κB/AIM2 signaling pathway while activating the NRF2/NQO1 pathway. In conclusion, this study demonstrates that resveratrol exerts anti-inflammatory and antioxidant effects, and protects neurological function by targeting the TLR4/NF-κB/AIM2 and NRF2/NQO1 signaling pathways. These findings provide a novel strategy for the neuroprotective treatment of stroke.