The immunological influence of physical exercise on TBI-induced pathophysiology: Crosstalk between the spleen, gut, and brain

•Traumatic brain injury (TBI) causes systemic inflammation and compromises the function of organs that regulate body response.•The spleen and gut are affected by TBI, and their response can exacerbate the neuroinflammatory damage of the injury.•The immune system seems to be the major connection between the brain, spleen, and gut.•Physical exercise can act as a non-pharmacological tool in post-injury treatment. Traumatic brain injury (TBI) is a non-degenerative and non-congenital insult to the brain and is recognized as a global public health problem, with a high incidence of neurological disorders. Despite the causal relationship not being entirely known, it has been suggested that multiorgan inflammatory response involving the autonomic nervous system and the spleen-gut brain axis dysfunction exacerbate the TBI pathogenesis in the brain. Thus, applying new therapeutic tools, such as physical exercise, have been described in the literature to act on the immune modulation induced by brain injuries. However, there are caveats to consider when interpreting the effects of physical exercise on this neurological injury. Given the above, this review will highlight the main findings of the literature involving peripheral immune responses in TBI-induced neurological damage and how changes in the cellular metabolism of the spleen-gut brain axis elicited by different protocols of physical exercise alter the pathophysiology induced by this neurological injury.