Role of mitochondrial dysfunction in acute traumatic brain injury: Evidence from bioinformatics analysis.

BACKGROUND

The intricate regulatory relationship between mitochondrial dysfunction, apoptosis, and immune cells remains largely elusive following traumatic brain injury (TBI).

METHODS

The GSE45997 dataset from the Gene Expression Omnibus database and utilized GEO2R to screen for differentially expressed genes (DEGs). Functional enrichment analyses were performed. Mitochondrial gene data from the MitoCarta3.0 database were combined with the DEGs to identify mitochondria-related DEGs (MitoDEGs). The hub MitoDEGs related to apoptosis were further screened. Animal models of TBI were established to investigate the mechanisms underlying mitochondrial dysfunction regulation of apoptosis. Furthermore, we explored the relationship between MitoDEGs/hub MitoDEGs and immune cells using the Spearman correlation method.

RESULTS

Fifty-seven MitoDEGs were significantly enriched in pathways related to fatty acid degradation and metabolism. We identified three upregulated hub MitoDEGs, namely , and , were associated with apoptosis. In the animal experiments, we observed significant expression levels of microtubule-associated protein 1 light chain 3 beta (LC3B) surrounding the injury site. Most LC3B-expressing cells exhibited positive staining for Beclin 1 and colocalization analysis revealed the simultaneous presence of Beclin 1 and caspase-3. The Western blot analysis further unveiled a significant upregulation of cleaved caspase-3 levels and LC3B II/LC3B I ratio after TBI. Moreover, the quantity of myeloid cell leukaemia-1 immunoreactive cells was notably higher than that in the control group. Spearman correlation analysis demonstrated strong associations between plasma cells, marginal zone B cells, native CD4 T cells, monocytes, and MitoDEGs/hub MitoDEGs.

CONCLUSIONS

This study sheds light on enhanced fatty acid metabolism following mitochondrial dysfunction and its potential association with apoptosis and immune cell activation, thereby providing new mechanistic insights into the acute phase of TBI.