Mechanism Of Nicotinamide Mononucleotide In Alleviating Neurological Function Impairment Induced By Traumatic Brain Injury

Objective Traumatic brain injury(traumatic brain injury,TBI),as one of the two major causes of death from multiple injuries,is a worldwide public health problem.Nicotinamide adenine dinucleotide(NAD)is a key metabolite that plays important biological functions in cellular bioenergy metabolism,genomic stability,mitochondrial homeostasis,and adaptive stress response.Previous studies have found that TBI can lead to a decrease in NAD~+level,so increasing NAD~+level in the body may become a potential method for TBI treatment.Nicotinamide mononucleotides(NMN)serve as precursors for NAD~+synthesis,and in vitro supplementation with NMN can rapidly increase NAD~+level in brain tissue.It has been shown that NMN can exert neuroprotective effects in stroke disease models,but its role in TBI has not been confirmed.This study aims to investigate whether NMN can exert neuroprotective functions in TBI rats through NMN treatment,and further explore its related molecular mechanisms.Methods Adult male Sprague-Dawley rats were randomly divided into three groups:Sham group;TBI group;TBI+NMN group.The electric controlled cortical impact(e CCI)was used to build TBI model in rats.TBI+NMN group were treated with NMN 1 hour after TBI.Then,the modified neurological severity score(m NSS)was used to evaluate the neural function of the rats,the Morris water maze(MWM)experiment was used to evaluate the learning and memory abilities of the rats,and pathological examination was performed on the brain tissue of the rats.At the same time,transcriptome sequencing was performed on rat hippocampal tissue.Rseults Behavioral experiments have shown that the neural function and spatial memory and learning ability of rats after TBI decrease.Pathological examination results show that brain tissue structure is disordered and a large number of neurons are gone.However,after NMN treatment,the behavioral results of TBI rats were significantly improved,and the tissue damage was reduced.Transcriptome sequencing results of rat hippocampal tissue showed that 1589 differentially expressed genes appeared in rats after TBI injury,including 1123 up-regulated and466 down-regulated.Compared with the TBI group,there were 854 gene expression changes in TBI+NMN,including 157 up-regulated and 697 down-regulated genes.792 DEGs that appeared after TBI were reversed after NMN treatment.The immunofluorescence results showed a decrease in the number of activated glial cells and apoptotic neural cells in the treatment group rats.PCR results showed the transcription levels of TNF-αand IL-1βin the treatment group rats decreased.Conclusion This study found that NMN treatment can improve neural function and spatial memory learning ability,reduce pathological damage,and inhibit inflammatory reactions.Some of the m RNA whose expression level changes after TBI is reversed after NMN treatment.These findings provide a new research direction for clinical treatment of TBI in the future.