Investigate the effects of salt diet on neuroinflammatory response, behavior, and microbiome dysregulation following repetitive closed head injury model.

Concussions continue to be a prominent public health concern, with an estimated 1.6-3.8 million incidences annually in the United States. Younger populations are experiencing the highest rates of concussion and nearly all athletic endeavors have some risk of concussive injury. Concerns surrounding the potential risks of long-term cognitive and medical outcomes made adolescent traumatic brain injury (TBI) a central focus of public attention. Coupled to these events, recent clinical studies have shown that lifestyle factors, including salt diet, constitute additional risk affecting TBI consequences and neuropathophysiological outcomes. However, the impact of salt diet on the pathophysiology of TBI and whether it exacerbates post-injury outcomes is still largely unknown.

We investigated if the exposure to a high salt diet (HSD) would alter hemodynamics, behavior, innate immune response and microbiome diversity after repetitive mild closed head injury in adolescent mice. Mice were injured with a three hit model (3HD) and then maintained on a HSD or standard diet (STD) for 12 weeks.

We found that HSD didn’t change systolic and diastolic blood pressure, and heart rate compared with STD group. HSD group was associated with worsening anxiety-like behavior at 12 weeks post diet administration. HSD induced microgliosis and proinflammatory microglial transcriptomic signature including upregulation in interferon gamma, Interferon beta, T cells proliferation pathways. Consistently, we found upregulation of proinflammatory Tumor necrotic factor (TNF) in brain compared to Sham-HSD and TBI-STD groups. HSD was the main driver of microbiome dysregulation in both TBI and Sham groups. We found that Eubacterium xylanophilum and Lachnospiraceae bacterium associated with an anxiety phenotype following injury at 12 weeks post diet administration.

Salt diet associated with increasing risk of worsening anxiety and exacerbating chronic neuroinflammation post repetitive head injury.