Increased cerebral uptake and oxidation of exogenous betaHB 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 beta-hydroxybutyrate (betaHB). Arterio-venous differences were used to determine global cerebral uptake of betaHB and production of 14CO2 from [14C]3-betaHB 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 betaHB showed no significant increase in cerebral uptake of betaHB or 14CO2 production. Increasing arterial betaHB concentrations 2.9-fold with 3 h of betaHB infusion failed to increase cerebral uptake of betaHB or 14CO2 production in adult sham animals. Only CCI animals that received a 3-h betaHB infusion showed an 8.5-fold increase in cerebral uptake of betaHB and greater than 10.7-fold increase in 14CO2 production relative to sham betaHB-infused animals. The TBI-induced 20% decrease in ipsilateral cortical ATP concentration was alleviated by 3 h of betaHB infusion beginning immediately after CCI injury.
Prins
M L
ML
Division of Neurosurgery, University of California at Los Angeles School of Medicine, Los Angeles, California 90095-7039, USA. mprins@mednet.ucla.edu
Lee
S M
SM
Fujima
L S
LS
Hovda
D A
DA
D020155:3-Hydroxybutyric Acid / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism*; D002245:Carbon Dioxide / Q000032:analysis / Q000378:metabolism; D002250:Carbon Radioisotopes; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D002250:Carbon Radioisotopes; D002245:Carbon Dioxide; D000255:Adenosine Triphosphate; D020155:3-Hydroxybutyric Acid