Resveratrol Reduces P38 MAPK Phosphorylation By Activating Sirtuin 1 To Alleviate Cognitive Dysfunction In Mice After Traumatic Brain Injury

Background: Traumatic brain injury（TBI）is accompanied by transient or permanent neurological dysfunction,characterized by neuronal loss and subsequent brain injury.Secondary brain injury after TBI is closely related to the recovery of cognitive dysfunction after TBI,and the main mechanisms are inflammation,oxidative stress,apoptosis and other major pathological symptoms.How to improve the prognosis of TBI is the key to the treatment of TBI.At present,many great progresses have been made in the research of TBI,but there is still a lack of using drugs to relieve neurological dysfunction after TBI,and new drugs or new factors need to be found.,and the use of certain interventions can alleviate the secondary injury after TBI.Resveratrol,a polyphenolic compound found in red grapes,red wine,and other plant foods,has been found to have many effects on inflammation,antioxidant stress,and vascular endothelial growth.The purpose of this study was to find out whether resveratrol is meaningful in the treatment of cognitive impairment after TBI.Objective: To observe whether resveratrol has significance in the recovery of nerve function in mice in the TBI model of mice,and to analyze SIRT1,synaptophysin,p38 MAPK,P-p38 MAPK and other proteins by Western blot.And its behavioral function was assessed by Y-maze to determine the efficacy of resveratrol on cognitive dysfunction in TBI.Methods: First,male mice aged 7-9 weeks were randomly divided into seven groups.One random group was the sham-operated group,and the other groups were established TBI models.The mice were killed by decapitation,and the right hippocampal protein was extracted from the mice to detect the expression of SIRT1 protein.The expression of SIRT1 protein decreased to the lowest level at 48 h,so the 48 h time point was selected for drug experiments.Then four groups of drug experiments were performed: sham operation group,TBI group,TBI + control group,TBI + resveratrol group.TBI + control group and TBI + resveratrol group were intraperitoneally injected with placebo dimethyl sulfoxide（3%,DMSO）and resveratrol（3%,5 ml/kg）at 3h and 24 h after TBI,respectively.48 h after TBI,the injured hippocampus of mice was extracted,and Western blot was performed to analyze SIRT1 protein,synaptophysin protein,p38 MAPK,P-p38 MAPK and other proteins.expression in the hippocampus.Finally,its behavioral function was evaluated by Y-maze to determine the curative effect of resveratrol on cognitive dysfunction in TBI.RESULTS: The expression of SIRT1 protein decreased to the lowest level at 48 h.At this point,drug experiments showed that resveratrol could activate the expression of SIRT1 protein,thereby inhibiting the phosphorylation expression of p38 MAPK,and finally the expression of synaptophysin in the hippocampus of mice increased.,synaptic function is restored.The Y-maze experiment showed that the neurological function of the mice was impaired after TBI,and the neurological function of the mice was restored after the use of resveratrol.Conclusions: Our study shows that the neuroprotective effect of resveratrol on cognitive ability after TBI is dependent on SIRT1 and its downstream molecule p38 MAPK.These new findings provide evidence for the clinical treatment strategy of resveratrol for cognitive impairment after TBI.