Increased cerebral uptake and oxidation of exogenous βHB improves ATP following traumatic brain injury in adult rats

There is growing evidence of the brain's ability to increase its reliance on alternative metabolic substrates under conditions of energy stress such as starvation, hypoxia and ischemia. We hypothesized that following traumatic brain injury (TBI), which results in immediate changes in energy metabolism, the adult brain increases uptake and oxidation of the alternative substrate β-hydroxybutyrate (βHB). Arterio-venous differences were used to determine global cerebral uptake of βHB and production of 14CO2 from [14C]3-βHB 3 h after controlled cortical impact (CCI) injury. Quantitative bioluminescence was used to assess regional changes in ATP concentration. As expected, adult sham and CCI animals with only endogenously available βHB showed no significant increase in cerebral uptake of βHB or 14CO2 production. Increasing arterial βHB concentrations 2.9-fold with 3 h of βHB infusion failed to increase cerebral uptake of βHB or 14CO2 production in adult sham animals. Only CCI animals that received a 3-h βHB infusion showed an 8.5-fold increase in cerebral uptake of βHB and greater than 10.7-fold increase in 14CO2 production relative to sham βHB-infused animals. The TBI-induced 20% decrease in ipsilateral cortical ATP concentration was alleviated by 3 h of βHB infusion beginning immediately after CCI injury.