Tetramethylpyrazine-2′O-sodium ferulate provides neuroprotection against neuroinflammation and brain injury in MCAO/R rats by suppressing TLR-4/NF-κB signaling pathway

Background: Neuroinflammation following cerebral ischemia is a serious risk factor in stroke patients. The purpose of this study was to investigate the neuroprotective effects of tetramethylpyrazine-2'O-sodium ferulate (TSF), a structurally modified compound from tetramethylpyrazine and ferulate, on cerebral ischemic injury and the underlying mechanisms. Methods: Focal transient cerebral ischemia was induced in rat for 2 h by middle cerebral artery occlusion (MCAO) and the protective effect of TSF was studied using different doses of the drug (10.8, 18, 30 mg/kg, intravenously); Ozagrel (18 mg/kg) was used as the positive control. The drugs were given immediately after MCAO and the efficacy and mechanisms were evaluated at 72 h of reperfusion. The level of pro-inflammatory cytokines such as TNF-alpha, IL-1 beta and anti-inflammatory molecules such as IL-10 was measured; other factors such as neurological deficit, brain water content and infarct size and the level of MCP-1, ICAM-1, iNOS, CD11b, TLR-4/NF-kappa Bp65 were also measured. Results: TSF at the doses of 18, 30 mg/kg significantly improved neurological deficit, reduced brain water content and infarct size, accompanied by a decrease in the concentration of TNF-alpha, IL-1 beta, MCP-1, ICAM-1, iNOS and an increase in the concentration of IL-10. The amount of CD11b and ICAM-1 was found largely decreased and the expression of TLR-4 and the nuclear NF-kappa Bp65 was weakened in TSF-treatment group. Conclusions: Our study suggests that TSF possesses a neuroprotective effect against ischemic stroke which might be mediated through suppression of the inflammatory pathways in the brain following ischemic stroke.