Strict Western Diet (WD) Induces Mild Metabolic Syndrome and Aggravates the Secondary Injury Pathophysiology in an Experimental Mouse Model of Traumatic Brain Injury.

Abstract

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 (e.g., diabetes, heart disease, hypertension) than the general population. WD has been shown to impair cognitive function and decreases the capacity of the brain to compensate for insult by affecting recovery. WD consumption induces metabolic syndrome (Mes) which may be a risk factor for poor TBI prognosis. Hence, this study aims to determine the potential of WD-induced Mes to aggravate TBI behavioral outcomes and neuropathology. Eight weeks old male C57BL6 mice were placed on either WD or normal chow (NC) diet for 4 weeks prior to TBI induction. At week four, mice were subjected to a controlled cortical injury (CCI) experimental TBI or sham procedure. After injury induction, mice continued on their respective diet for four weeks. Neurological and cognitive evaluations were assessed by a battery of tests including pole climbing, grip strength, rotarod, and Morris water maze (MWM) before sacrifice. To assess cardiovascular function, echocardiography and blood pressure were measured, and fat percentage was assessed by Nuclear Magnetic Resonance (NMR) before and after brain injury. Blood glucose was examined weekly for 8 weeks. In addition, mitochondrial function, plasma cholesterol, neuroinflammation, and neurodegeneration were investigated. Results showed that WD significantly increased fat percentage, elevated plasma cholesterol, induced neuroinflammation, and impaired cognitive functions. However, there was no significant impact on cardiovascular function and mitochondrial bioenergetics. Taken together, our work indicated that WD can exacerbate the neuropathology of TBI, and alter behavioral outcomes; however, other physiological changes were shown to be mildly affected. Further research is needed to assess these changes.