Resveratrol Attenuates Endoplasmic Reticulum Stress-Induced Cell Death and Results in Functional Improvement after Traumatic Brain Injury in Mice

Resveratrol (RSV), a polyphenol antioxidant, has been reported to function as a neuroprotector.We explored the molecular mechanisms that underlines the anti-inflammatory activity of RSV in traumatic brain injury (TBI) in mice relevant to endoplasmic reticulum stress (ERS).By establishing three experimental groups (sham, TBI, and TBI+RSV), we examined the effects of RSV after TBI on ERS and caspase-12 apoptotic pathways cascades.The protein expressions levels of C/EBP homologous protein (CHOP), glucose regulated protein 78kD (GRP78), caspase-3, and caspase-12 in cortical brain tissues were evaluated by western blotting.The cortical brain tissues were also subjected to a qPCR analysis of mRNA expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β.Additionally, immunofluorescence staining was used to determine the expression of GRP78 in microglia (ionized calcium binding adaptor molecule 1;Iba-1) and neurons (neuronal nuclei;NeuN).The neurological function of the mice was analyzed based on modified neurological severity scores (mNSS).After RSV treatment, the expression of CHOP, GRP78, caspase-3 and caspase-12 decreased, and qPCR results showed downregulation of TNF-α and IL-1β.Immunofluorescence stain demonstrated Iba-1 + /GRP78 + and NeuN + /GRP78 + cells decreased after RSV treatment.The mNSS analysis indicated improvement following RSV treatment.RSV alleviated neuro-apoptosis by inhibiting the ERS signaling pathway and also improved the neurological function of mice with TBI.