Cerebral ketone metabolism during development and injury

Abstract

Cerebral metabolism of ketones is a normal part of the process of brain development. While the mature brain relies on glucose as a primary fuel source, metabolism of ketone bodies remains an alternative energy source under conditions of starvation. The neuroprotective properties of brain ketone metabolism make this alternative substrate a viable therapeutic option for various pathologies. Since the ability to revert to utilizing ketones as an alternative substrate is greatest in the younger post-weaned brain, this particular therapeutic approach remains an untapped resource particularly for pediatric pathological conditions.

Figure 1

Changes in plasma concentrations of ßOHB with time after TBI in PND35 (grey bars) and PND75 (black bars) rats maintained on the KG diet after injury. PND35 animals achieve higher levels of ßOHB earlier than PND75 animals. Data is expressed as mean ±sem. *, ** p<0.05, 0.01 relative to age-matched sham

Figure 2

Concentration of cytosolic NAD+ (nmol/μg) in PND35 and PND75 rats at 6, 12, 24hrs post injury. Animals were given sham or CCI injury and at 6,12,or 24 hrs after injury brains were rapidly removed, the cortical tissue dissected and homogenized ice cold homogenization media (0.25 sucrose, 3mM Tris, pH 7.4,1mM EGTA) with a Dounce homogenizer. The homogenate was centrifuged at 17,000g at 4°C for 10min. The cytoplasmic fraction was removed and analyzed for NAD⁺ concentrations (Nisselbaum and Green,1969). Cytosolic NAD⁺ decreases significantly after TBI in both age groups and will likely contribute to glycolytic inhibition via GAPDH.