Evaluating Causative Effects of Single/Multiple Neurotrauma on Neurodegeneration

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 DESCRIPTION (provided by applicant): Increasing numbers of US Veterans are returning from military ventures suffering from blast exposure and traumatic brain injury (TBI). There is a critical need for a greater understanding of the long term and debilitating impairments in cognition, psychological health, and sensorimotor abilities. To further complicate the injury, combat personnel exposed to repeated concussions could find themselves with long-term sequelae. A significant number of these individuals are presenting with clinical symptoms of neurodegenerative diseases and cognitive decline. The number of these individuals is increasing with the current war and poses a major challenge for the Department of Veterans Affairs. Answers to fundamental neuroscience questions about the etiology of neurodegeneration in Veterans exposed to combat-related stress and TBI are lacking. Furthermore, it is not known how the acute injury progresses into a chronic pathology and symptomatology. With the large number of Veterans reported to have TBI, it is vital to study the long-term effects of TBI as it relates to the sequelae of neurological events following single or multiple exposures to trauma. One of the goals of this research is to establish a biological basis for identifying chronic TBI which could have a significant effect on diagnosis and differentiation from other neurological conditions. This ability could significantly benefit the patient diagnosis and differentiate it from other neurological conditions. The ultimate goal is to determine if various brain injury mechanisms advance the progression of memory loss and neurodegeneration. The research design involves experimental models of blast TBI. Using military-relevant neurotrauma rodent models, we expect to accomplish the following Specific Aims; (1) to establish the longitudinal effects of both single and multiple injuries in utilizing neurocognitive and behavioral assessments (2) to identify chronic biomarkers which correlate with neurodegeneration following single and repeated injuries and (3) to validate the progression of neurodegeneration using histological and molecular techniques. Understanding the long term consequences of neurotrauma and identifying the mechanisms underlying the transition from acute to chronic pathology will help to more effectively identify, treat and optimie rehabilitative strategies for our Veterans with TBI. Recent advances across our laboratories have demonstrated efficacy of rodents to model military-related TBI including multiple mild TBIs. However, data on long term outcomes are lacking and are required to most effectively provide rehabilitation strategies catering to the individual stage of injury and neurodegeneration progression. The ability to understand and measure injury progression makes this research highly relevant to the VA mission.