Resveratrol prevents cognitive impairment and hippocampal inflammatory response induced by lipopolysaccharide in a mouse model of chronic neuroinflammation.

BACKGROUND: Neurodegenerative disorders are associated with chronic neuroinflammation, which contributes to their pathogenesis and progression. Resveratrol (RSV) is a polyphenolic compound with strong antioxidant and anti-inflammatory properties. In the present study, we investigated whether RSV could protect against cognitive impairment and inflammatory response in a mouse model of chronic neuroinflammation induced by lipopolysaccharide (LPS). METHOD: Mice received oral RSV (30 mg/kg) or vehicle for two weeks, and injected with LPS (0.75 mg/kg) or saline daily for the last seven days. After two weeks, mice were subjected to behavioral assessments using the Morris water maze and Y-maze. Moreover, mRNA expression of several inflammatory markers, neuronal loss, and glial density were evaluated in the hippocampus of treated mice. RESULTS: Our findings showed that RSV treatment effectively improved spatial and working memory impairments induced by LPS. In addition, RSV significantly reduced hippocampal glial densities and neuronal loss in LPS-injected mice. Moreover, RSV treatment suppressed LPS-induced upregulation of NF-κB, IL-6, IL-1ß, and GFAP in the hippocampus of treated mice. CONCLUSION: Taken together, our results highlight the detrimental effect of systemic inflammation on the hippocampus and the potential of natural products with anti-inflammatory effects to counteract this impact.

Gamma-oryzanol attenuates lipopolysaccharide-induced cognitive impairment by modulation of hippocampal inflammatory response and glial activation in mice.

Systemic inflammation can cause chronic neuroinflammation, which is a significant risk factor for neurodegenerative disorders. Therefore, anti-inflammatory agents that reduce peripheral inflammation are potential targets for the prevention or treatment of these debilitating diseases. In the present study, we investigated whether gamma-oryzanol (ORY) could protect against chronic neuroinflammation induced by lipopolysaccharide (LPS) in adult male mice. Mice were injected with LPS (0.75 mg/kg/day) or saline for 7 consecutive days and orally received ORY (100 mg/kg) or vehicle for 14 days (7 days before LPS injections and 7 days co-treated with LPS). After two weeks, mice were subjected to behavioral assessments using the Morris water maze and Y-maze. Moreover, the expression level of several inflammatory mediators was measured in the hippocampus of treated animals. Also, neuronal loss, microglia, and astrocyte densities were evaluated in the CA1 and CA3 hippocampus. We found that ORY treatment significantly improved spatial and working memory in LPS-treated mice. This behavioral improvement was accompanied by a significant reduction in the number of microglia and astrocytes in the CA1 and CA3 hippocampus. Moreover, ORY treatment effectively prevented LPS-induced increases in the expression of inflammatory mediators and enhanced neuronal survival in the CA1 hippocampus. Our findings suggest that ORY treatment can be a therapeutic option to improve cognitive impairments and neuroinflammation induced by endotoxins.