Impacts of Secondary Insults after Traumatic Brain Injury: Future Therapeutic Targets

Dear Colleagues,

Traumatic brain injury (TBI) leads to chronic debilitating neurodegeneration and long-term neurological outcomes which are strongly affected by cerebral and secondary organ effects of TBI that drive and enhance neuroinflammation.

Hypoxia and neuroinflammation are secondary cerebral insults observed within 24 hours after TBI that increase morbidity and mortality. TBI also impacts distant organs by inducing systemic secondary alterations, including the gastrointestinal tract (GI), the kidneys, and the immune system that negatively affect TBI outcomes. However, the molecular mechanisms of interorgan crosstalk involved after TBI are unknown. TBI induces alterations of the central and systemic immune systems that can impact remote organs after injury. In TBI, patients often present with GI dysfunction such as increasing gut barrier permeability, decreasing gut motility, and alterations of the gut microbiome. Furthermore, TBI in mice with gut microbial dysbiosis (using antibiotics) induced microglial activation, a decrease of hippocampal neurogenesis, and a reduction of T cell infiltration demonstrating the essential role of T cells in gut-brain communication. In addition, TBI in the elderly has been exacerbated by the co-occurrence of acute kidney injury (AKI), suggesting TBI-induced systemic inflammation as a possible mechanism of AKI after injury. Neuroprotective therapeutic approaches to mitigate the secondary cerebral injury, such as erythropoietin and minocycline, have been effective in several preclinical studies. However, the therapeutic efficacy of these agents in clinical trials have failed to improve TBI outcomes. Therefore, we need a deeper understating of the mechanisms that underlie TBI-induced changes in immunity and the impact of both central and remote organ inflammation on TBI outcomes as an avenue for therapeutic intervention in the setting of TBI. We encourage submitting original papers, reviews, and perspectives on new therapies for this special issue.

Marta Celorrio
Guest Editor

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