Exercise-induced molecular modulation following mTBI: A multi-omics study in male mice.

Mild traumatic brain injury (mTBI) poses a significant clinical challenge, often resulting in persistent cognitive and neurological impairments. This study investigates the therapeutic effects of a 17-day running protocol on mTBI recovery in male mice. Using a weight-drop mTBI model, proteomics and RNA-sequencing analyses were conducted at acute (19 days post-injury) and chronic (47 days post-injury) time points. mTBI induced significant changes in both protein and gene expression, primarily affecting pathways related to neuronal function, neurogenesis, and synaptic plasticity. Running protocol effectively mitigates acute and chronic molecular changes associated with mTBI, promoting neuroprotection and neuroplasticity. Proteomics and gene expression analyses revealed significant improvements in pathways related to neuronal repair, synaptic function, and neurogenesis. Specifically, running normalized the expression of key proteins such as DNAH5, PPP1CC, CPNE7, ATG7, and RanBP9, which are involved in processes like synaptic plasticity, neurogenesis, mitochondrial function, and blood-brain barrier integrity. In addition, two DEPs (FDX2 and SGIP1) demonstrated recovery processes comparing the mTBI + running group with the mTBI group. The results suggest that running may be a valuable therapeutic strategy for promoting brain repair and functional recovery post mTBI.