The Neuroimmune Nexus: Diet-Induced Obesity, Inflammation, and Diet-Modulated Recovery Following Traumatic Brain Injury.

Traumatic brain injury (TBI) is a prevalent chronic disorder associated with progressive neurological decline. Due to the highly heterogeneous nature of TBI, treatment and care pose a significant challenge. Recent developments in the multidimensional classification framework of TBI suggest that patient-related factors (e.g., sex, age, and medical history, including body weight and pre-existing comorbidities) and injury-related factors (e.g., comorbid extracranial injury, secondary insults, and injury mechanism) need to be taken into consideration for the development of targeted treatment strategies and comprehensive care for TBI patients. To this end, there is now a substantial body of evidence that body weight and pre-existing obesity may be a critical, yet modifiable, patient-related factor associated with worsened TBI outcomes. It is hypothesized that obesity is characterized by a state of chronic low-grade systemic inflammation that primes both peripheral and central immune responses, rendering the individual particularly vulnerable to the negative consequences of TBI. In contrast, specific dietary patterns such as the Mediterranean diet, ketogenic diet, and dietary restriction may attenuate inflammatory processes and exert neuroprotective effects on TBI outcomes. In this review, we synthesize pre-clinical and clinical evidence highlighting the complex relationship between diet and TBI outcomes. We explore how obesity-induced peripheral inflammation may serve as a viable target to alleviate negative outcomes in TBI subpopulations with pre-existing metabolic dysfunction. In addition, we discuss how modification of dietary patterns may serve as a clinically relevant, non-pharmacological strategy to reduce the negative sequelae of events following exposure to TBI.