Adequate consumption of polyunsaturated fatty acids (PUFA) is vital for neurodevelopment and neuroprotection. Previously, we established a mouse model where the brain DHA was moderately reduced (by about 30-35%) to a human relevant level (DPAn-6 to DHA ratio of 0.4) by providing a low -linolenic acid (ALA) diet, and demonstrated that increasing the brain DHA level even from a moderately DHA-depleted state can reduce neuroinflammation and improve functional recovery after TBI induced by controlled cortical impact (CCI). During this period, we used the repetitive Closed-Head Impact Model of Engineered Rotational Acceleration (rCHIMERA) model which recently has been shown to generate clinically relevant head injuries, to evaluate the effects of brain DHA status on the behavioral and histologic outcome after TBI. Mice at 4-5 months age were anesthetized with 5% isoflurane and injured by a CHIMERA impact delivered medially at about 0.55J for three consecutive days with each injury given 24 h apart. Morris water maze test was performed at 4 months after injury to evaluate cognitive function. Although statistical significance was not reached, moderate DHA-deficiency or rCHIMERA injury produced a trend of decreasing performance with reduced time and distance in the platform quadrant. Moderately DHA-depleted injured (Deficient rCHI) mice showed significantly impaired performance compared to DHA-adequate sham (Adequate Sham, p=0.003) and nearly significant decline compared to the DHA-adequate injured group (Adequate rCHI, p=0.06), particularly in the measure of platform crossings. As modern diets have low omega-3 fatty acids and can lead to moderate DHA deficiency in humans, results from this study may present strong possibility of using nutritional remediation as a tool to enhance recovery from brain injury. Neuroinflammation caused by TBI assessed by immunostaining of GFAP and Iba-1 was markedly elevated after rCHIMERA in corpus callosum (CC), optic tract (OT) and hippocampal (HC) regions particularly from moderately DHA-deficient animals. This elevation was significantly lower (in CC and OT) or completely blocked (in HC) in DHA-adequate brains. These results suggest that raising the brain DHA status from the level commonly found in humans may be protective at least for neuroinflammation and memory deficit caused by rCHIMERA. We have also observed through a combination of behavioral and electrophysiological studies that vision is compromised in adult mice subjected to one closed head injury using CHIMERA model for three consecutive days. It was observed that two repeated injuries are sufficient to induce changes in visual evoked potential (VEP), indicating that more than one TBI may result in impaired visual function.
|Chen, Huazhen; Desai, Abhishek; Kim, Hee-Yong (2017) Repetitive Closed-Head Impact Model of Engineered Rotational Acceleration Induces Long-Term Cognitive Impairments with Persistent Astrogliosis and Microgliosis in Mice. J Neurotrauma 34:2291-2302|
|Desai, Abhishek; Park, Taeyeop; Barnes, Jaquel et al. (2016) Reduced acute neuroinflammation and improved functional recovery after traumatic brain injury by ?-linolenic acid supplementation in mice. J Neuroinflammation 13:253|
|Desai, Abhishek; Kevala, Karl; Kim, Hee-Yong (2014) Depletion of brain docosahexaenoic acid impairs recovery from traumatic brain injury. PLoS One 9:e86472|
|Kim, Hee-Yong (2014) Neuroprotection by docosahexaenoic acid in brain injury. Mil Med 179:106-11|