Dynamic evolution of molecular pathological mechanism of mouse brain tissue after seawater immersion combined with traumatic brain injury:a multi-time-point proteomics analysis

WANG Bingxian; XIE Shengqiang; HE Renke; ZHANG Hanbo; CHENG Gang; ZHANG Jianning

doi:10.3639/j.issn.1671-2897.2025.03.008

Abstract：Objective To explore the dynamic impact of seawater immersion on the multi-stage pathological process of traumatic brain injury(TBI),and to analyze the molecular mechanism of its synergistic injury,providing a theoretical basis for the development of time-specific treatment strategies.Methods A TBI mouse model(TBI group)and a seawater immersion combined with TBI mouse model(TBI+SWI group)were established by controlling the cortical impact injury(CCI)model combined with artificial seawater(37℃,ph 8.2±0.1).Cortical samples from the injured mice were collected for proteomic analysis at 1,3,7 and 28 days after successful modeling in each group.Database retrieval was conducted through MaxQuant to screen the differential proteins in the brain tissues of the TBI+SWI group and the TBI group,and the R language was used for analysis.The time series expression patterns of differentially expressed proteins were clustered and analyzed by the Mfuzz algorithm.Results Compared with the TBI group,the differentially expressed proteins in the brain tissue of the loss area in the TBI+SWI group mice during the acute phase included MAN2B1,TNFA1P8,MPO,ITGB1,etc.,suggesting that lysosomal dysfunction and mitochondrial damage were aggravated,neutrophil chemoattraction-related proteins were significantly upregulated,pro-inflammatory factors increased,and complement components also reached their peaks in the early stage,all of which indicated the inflammatory storm and the disruption of the blood-brain barrier.The differentially expressed proteins that appeared in the brain tissues of mice in the TBI+SWI group during the subacute stage included IL6ST,COX-1,GRIA4,etc.,suggesting delayed activation of autophagy-related proteins,upregulation of the PI3K-PKB pathway to drive repair,but the chronic inflammatory markers continued to increase and the glutamate receptor was downregulated.The differentially expressed proteins in the TBI+SWI group mice during the chronic phase included MTUS2,DYN2CI1,SOD1,MAPT,etc.,suggesting the down-regulation of cytoskeletal proteins and ubiquitin-proteasome components.Time cluster analysis further divided the protein expression in the brain tissues of mice in the TBI+SWI group into 10 functional modules,revealing the molecular basis of the main pathological processes at different times.Conclusions There is a three-stage dynamic mechanism of seawater immersion combined with craniocerebral injury through proteomics,which worsens the course of the disease by aggravating immune activation,ion dysregulation,and inhibition of repair pathways,and increases the risk of neurodegeneration.This model provides a new theoretical basis and research direction for the treatment of seawater immersion combined injury.