Blast-induced traumatic brain injury (TBI) is an increasingly prevalent health concern in the military population, with many personnel exposed to blast overpressure from improvised explosive devices. Following an injury, Service members and Veterans can display acute neurological impairments and long-lasting cognitive and behavioral symptoms. However, the underlying cellular changes that occur after blast TBI and some of the cognitive changes that occur are not fully understood. Furthermore, the impact of nutrition on recovery following blast TBI has not commonly been a focus of research studies. Both moderate and severe blast-related TBIs have been shown to change mitochondrial metabolism, increase oxidative stress, and increase cell death up to 48 hours following injury. However, there is not much information on the cellular changes that occur, which impact the use of energy substances within the cell such as the use of glucose for mitochondrial function and cellular respiration. The limited blast-related studies that have been performed show that energy use changes following blast and there is also evidence of increased reactive oxygen species production and oxidative stress, as well as cell apoptosis in rodents. To better understand the cellular changes that occur following blast injury, we must first understand the changes that occur to basic cellular processes. In a normal functioning cell, glucose is the main sugar used for cellular processes and to power the mitochondria, which provide energy to the cell and whole organism. Following TBI, a cascade of cellular changes occur within the brain, starting with increased release of glutamate, an excitatory molecule, followed by cell membrane depolarization. The brain then enters a state of increased glucose utilization that results in separating glucose processing from cellular respiration, followed by reduced cerebral glucose metabolism and cellular energy dysfunction. These changes ultimately lead to reduced mitochondrial oxygen consumption, increased reactive oxygen species production, and decreased energy production. These factors ultimately result in an imbalance of energy production and decreased cellular metabolism, leading to cell death and poor cognitive function. In this scenario, the use of an alternative energy substrate, such as ketone bodies (beta-hydroxybutyrate, acetoacetate, and acetone) provide energy sources for the cell that can be used in place of glucose. The novel Ketone Ester (KE) supplement is a source of all three ketone bodies, which enhance mitochondrial efficiency, decrease reactive oxygen species production, and improve cognitive function. Previous work demonstrates the benefits of individual ketone bodies via increased energy production as well as decreased cell death. Our proposed research will address the Topic Area of Nutrition Optimization by answering the question, “Can the use of KE as a dietary supplement reverse cellular and mitochondrial changes that occur following blast TBI?”

To answer this question, we will assess the effect of KE as a dietary supplement in a blast TBI rodent model. We will expose rodents to either a mild or moderate repeated blast and then provide KE supplementation in addition to their normal diet. We will also include some behavioral tests to determine how the blast and KE supplementation affect thinking and movement. We will examine how long-lasting any changes are by assessing the rodents at 4 hours, 24 hours, and 2 weeks after the last blast exposure. We expect the KE supplement will provide a benefit to the blast-exposed rodents and improve their recovery time, their mitochondrial activity, and their thinking and movement.