Lab Manager Parsons Corporation/Naval Medical Research Center Silver Spring, Maryland
Abstract Text: Blast induced traumatic brain injury (bTBI) remains a health concern facing military personnel. bTBI is associated with cerebral glucose metabolism dysregulation. The resulting energy deficit from bTBI may increase oxidative stress and the onset of a cascade of pathological processes that exacerbate the injury. As an alternative to glucose-dependent diet, a ketogenic diet (KD) or a ketone ester supplemented standard diet make ketone bodies readily available for break down and could alleviate the effects of impaired glucose metabolism resulting from trauma. This study examined the impact of pre-blast treatment with a KD or ketone ester supplement on oxidative stress and neuronal damage using a rat model of bTBI. Rats were pre-treated with KD, SD, or SD with 20% ketone ester (KESD) by weight for 14 days with periodic monitoring of body weight, blood glucose, and blood ketone levels to determine if rats entered the state of ketosis, followed by exposure to 110 kPa blast. Animals were euthanized 24 hours after blast exposure and brains were harvested for assessment of oxidative stress and neuronal degeneration. KD and KESD fed rats showed elevated blood ketones and significantly decreased body weight relative to SD fed rats, indicating these rats attained the state of ketosis. Blast exposed animals with KD or KESD showed a reduction in reactive oxygen species in the frontal cortex in comparison to blast-SD animals. No significant differences due to diet treatment were seen on other markers (nitric oxide, total antioxidant capacity, and the ratio of reduced to oxidized glutathione) of oxidative stress. Immunohistochemistry analyses found significantly decreased 3-Nitrotyrosine and inducible nitric oxide synthase expression in the frontal cortex of KD and KESD fed rats relative to SD fed blast exposed rats, indicating KD and KESD pre-blast treatment has beneficial effects in reducing oxidative stress. Fluoro-Jade cell staining also showed significant decreases in Fluoro-Jade positive cells in KD and KESD fed rats relative to SD-fed blast exposed rats, indicating that ketosis confers increased neuronal resilience in the cortex following blast exposure. These results indicate that diet conditioning with KD or KESD prior to blast exposure may be beneficial in ameliorating blast related oxidative stress and neuronal degeneration. Disclaimers: The views expressed in this abstract reflect the results of research conducted by the author and do not necessarily reflect the official policy or position of the of The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Parsons Corporation, the Department of the Navy, or the Department of Defense (DoD). Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. Government. This work was supported/funded by Office of Naval Research Sponsored In-house Laboratory Independent Research. The study protocol was reviewed and approved by the Walter Reed Army Institute of Research/Naval Medical Research Center Institutional Animal Care and Use Committee in compliance with all applicable Federal regulations governing the protection of animals in research. The experiments reported herein were conducted in compliance with the Animal Welfare Act and per the principles set forth in the "Guide for Care and Use of Laboratory Animals," Institute of Laboratory Animals Resources, National Research Council, National Academy Press, 2011 Some of the authors are military service members or federal/contracted employees of the United States Government This work was prepared as part of their official duties. Title 17 U.S.C. § 105 provides that 'Copyright protection under this title is not available for any work of the United States Government.' Title 17 U.S.C. § 101 defines a U.S. Government work as a work prepared by a military service member or employee of the U.S. Government as part of that person's official duties.
