Graduate Student Uniformed Services University Bethesda, Maryland
Abstract Text: Although traumatic brain injury (TBI) affects millions of people each year, it remains a critical public health problem with no standard therapeutic treatment. Lasting functional and behavioral deficits have detrimental effects on the quality of life for TBI patients. A main target for treatment is post-TBI secondary injury, which is the disruption of normal cellular processes and inflammatory effects caused by the initial injury. Ketamine, a potent analgesic and anesthetic medication, is often administered to victims at the scene of traumatic injury and has been shown to have anti-inflammatory properties. However, ketamine’s treatment effect on post-TBI secondary injury, which includes behavioral and inflammatory outcomes after TBI, is not well characterized. Improving treatment options for post-TBI secondary injury could reduce functional and behavioral deficits and improve the quality of life for TBI patients. For the current study we used the Closed Head Impact Model of Engineered Rotational Acceleration (CHIMERA), a recently developed technique that replicates the biomechanical mechanism of how humans sustain a closed-head impact TBI from resulting free head movement. Adult male Sprague-Dawley rats with indwelling jugular venous catheters sustained repetitive CHIMERA impacts (sham or 3 x 1.5 J) in a single session and were given either intravenous saline, 10 mg/kg ketamine, or 20 mg/kg ketamine in a two-hour infusion one hour post-TBI. Catheter blood samples were collected at baseline, 1, 3, and 5 hours, and 1, 2, 3, and 4 days after CHIMERA. Behavioral metrics included rotarod, activity, acoustic startle reflex, and pre-pulse inhibition (ASR/PPI). Animals were euthanized on day 4 post-injury and brain tissue was collected for analysis. Ketamine dose-dependently affected activity levels of animals during the infusion. CHIMERA-injured animals showed deficits on the rotarod test, 3 days post-injury and mild effects in other behavioral testing. Consistent with previous studies, ketamine reduced inflammatory cytokines after injury at both dosages. The examination of activated glial cells in brain tissue is in progress. A single session of repeated impacts using a CHIMERA paradigm produced a mild TBI phenotype with mild behavioral effects. Post-injury ketamine administration induced immunomodulatory effects. This study indicates that a subanesthetic ketamine infusion after TBI does not have detrimental effects on outcomes. Supported by TriService Nursing Research Program (TSNRP) and Center for the Study of Traumatic Stress (CSTS). The views represented are those of the authors and do not reflect policy of the Henry M. Jackson Foundation for the Advancement of Military Medicine Inc, the US Government, Department of Defense, US Navy, or USU.
