Screening And Verification Biomarkers After Traumatic Brain Injury With Quantitative Proteomics

Objective: Traumatic brain injury(TBI)is considered one of the most influence disease on death and disability,causing psychological burdens for patients.The secondary injury occurs in hours and days after the initial injury,caused a series of neurological events,including immune respond,excitotoxicity,hydrocephaly.In clinic,the essential of diagnose about TBI is medical imaging,such as CT and MRI.It is hardly to monitor the development and recovery dynamically,because of the lack of specific biomarkers.In addition,the mechanism of neurondegenerative and sequela of TBI are still unknown.In this study,we aimed to analysis the metabolic change of TBI via quantitative proteomics and bioinformation,to determine the potential biomarkers and relationship with pathways after TBI,and to establish a multiplex proteomics way for determination of post traumatic interval after TBI.Methods: SD rat TBI model was established by weight drop device.For discussion the change of proteomics,seventy-five male rats were divided into five groups including control group and four time-points TBI groups(1h,6h,24 h,3d).The injured cortex tissues were collected and undergone LC-MS/MS.After suffering TBI,the proteins with expression ratio of over 1.2-fold in increase or at least 0.8-fold in decrease were considered as significant difference.Gene Ontology(GO)and pathways analysis were performed by DAVID,Panther Database bioinformation tools.According to the results of bioinformation,potential biomarkers and pathways were selected and verified.Results: The proteomics was changed significantly after suffering TBI,and participated in pathways diversity.Ubiquition proteasome pathway,glycolysis and Wnt signaling pathway were chose for further analysis.For biomarker survey,we found PSMC4,Hexokinase-1 were increased 1 h after TBI,and AP2M1 was decreased at 3rd day after suffering TBI.In primary neuron culture,compared with control group(without LPS treatment),the neuron was treatment with LPS could depressed Wnt signaling pathway,meanwhile,promoted cell apoptosis.However,apoptosis was decreased by Wnt signaling activation.Conclusions: After TBI,the profile of proteomics was changed,and a lot of biological processes and pathways were participated in injury regulation.PSMC4,Hexokinase-1,AP2M1 were screened as potential biomarkers for acute-phase injury.Aopptosis of TBI could be regulated by Wnt signaling.