Western diet induces mild metabolic impairment and aggravates neuropathology in an experimental mouse model of traumatic brain injury

Traumatic brain injury (TBI) and lifestyle habits such as Western diet (WD) consumption represent two risk factors that affect an individual's health outcome globally. Individuals with TBI have a greater risk of mortality from associated chronic diseases than the general population. WD has been shown to impair cognitive function, decrease the brain's capacity to compensate for insult by affecting recovery as well as induce metabolic syndrome (MetS) which may be a risk factor for poor TBI prognosis. Hence, this study aims to investigate the impact of WD on TBI behavioral outcomes and neuropathology. Eight-week-old male C57BL6 mice were fed either WD or normal chow for 4 weeks prior to TBI induction. At week four, mice underwent either an experimental open-head TBI or a sham procedure. Mice continued their respective diets for four weeks after brain injury. Metabolic, cognitive function, and molecular assessment were performed four weeks after TBI. Results showed that while WD significantly increased fat percentage and elevated plasma cholesterol, there was no change in blood glucose level or body weight, indicating an early stage of MetS. Nevertheless, this was associated with neuroinflammation and impaired cognitive functions. However, there was no significant impact on cardiovascular function and mitochondrial bioenergetics. Importantly, the mild MetS induced by WD triggered basal motor, cognitive deterioration and exacerbated the long-term neuropathology of TBI. Taken together, our work highlights the magnitude of the contribution of lifestyle factors including the type of diet, even in the absence of overt metabolic consequences, on the neurobehavioral prognosis following TBI.