Ketone Body Administration to Treat Spinal Cord Injury

Hypothesis. The current proposal will test the hypothesis that treatment with the ketone body, ?-hydroxybutyrate (BHB), will significantly reduce mitochondrial oxidative damage and, thus, improve mitochondrial energy metabolism to foster increased neuroprotection and maximize hindlimb functional recovery following contusion spinal cord injury (SCI). Objective of the project. We have reported that contusion SCI triggers a progressive loss of mitochondrial bioenergetics over 24 hr post-injury, which is accompanied by increased reactive oxygen species (ROS) production. Notably, however, we have found that maintenance of mitochondrial bioenergetics by administering an alternative biofuel, acetyl-l-carnitine (ALC), fosters both neuroprotection and functional recovery after contusion SCI. ALC increases acetyl-CoA levels in mitochondria, which then enters into the citric acid cycle and forms NADH that is used by the mitochondrial electron transport chain (ETC) for ATP production. Therefore, our recent findings provide compelling evidence that ALC supplementation after SCI serves as an alternative biofuel for mitochondria whose integrity is compromised after trauma.