A new ketogenic formulation improves functional outcome and reduces tissue loss following traumatic brain injury in adult mice

Rationale: Traumatic brain injury (TBI) leads to neurological impairment, with no satisfactory treatments available. Classical ketogenic diets (KD), which reduce reliance on carbohydrates and provide ketones as fuel, have neuroprotective potential, but their high fat content reduces compliance, experimental evidence suggests they protect juvenile against TBI, not adult brain, would strongly limit applicability in TBI. Methods: We designed a new-KD carbohydrate plus protein ratio of 2:1, containing medium chain triglycerides (MCT), docosahexaenoic acid (DHA), low glycaemic index carbohydrates, fibres the amino leucine, evaluated its potential Adult male C57BL6 mice were injured by controlled cortical impact (CCI) assessed for 70 days, during received control diet or new-KD. Results: The new-KD, that markedly increased plasma Beta-hydroxybutyrate (?-HB), significantly attenuated sensorimotor deficits corrected spatial memory deficit. lesion size, perilesional inflammation oxidation reduced. Oligodendrocyte loss appeared be TBI activated mTOR pathway enhanced this increase histone acetylation methylation. Conclusion: behavioural improvement tissue protection proof principle new formulation has therapeutic