During this period, we have tested the effect of the brain DHA status on the recovery from TBI. We generated animals with different magnitudes of omega-3 fatty acid deficiency by single or multigenerational feeding regimen and the impact of such deficiency on the TBI outcome was evaluated. The brain DHA level was lowered by 30- 70%, which was mostly compensated by the increase of docosapentaenoic acid (DPA, 22:5n-6). Age and gender matched mice at 10-12 weeks from adequate and deficient groups were subjected to the controlled cortical impact (CCI) procedure and the TBI-induced motor and congnitive deficits were evaluated. We found that the motor function of omega-3 adequate animals assessed by rotarod and beam walk tests was recovered by day 2 after TBI while the deficient group showed prolonged motor deficit until day 4 after TBI. The cognitive function evaluated by the novel object recognition test also indicated a more severe deficit after TBI in the deficient group. Biochemically, a decrease in synapsin-1 expression was confirmed in the mice with severe omega-3 depletion, which was exacerbated by TBI. TBI also increased the levels of cleaved -spectrin in the injured cortex of the deficient mice as compared to the adequate TBI group. Moreover, there were decreased NeuN positive cells in the cortex of the deficient mice near the site of injury compared to the adequate TBI mice. These results indicate that omega-3 fatty acid deficiency renders the brain more vulnerable to the effects of injury, and together with the results from behavioral tests, may imply that such deficiency hampers recovery from TBI. The mice with moderate omega-3 fatty acid deficiency also showed impaired recovery in motor tests and more anxiety-like behavior, indicating that injury outcome is negatively influenced even with moderate deficiency. Fear conditioning paradigm, which has been used to assess the fear response in TBI, revealed that TBI mice show exaggerated response to contextual conditioning as compared to sham injured mice, thereby indicating that brain injury impairs normal fear response. This fear conditioning paradigm will be subsequently used to evaluate the fear response in TBI mice with different DHA status in brain.

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National Institute on Alcohol Abuse and Alcoholism
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Desai, Abhishek; Kevala, Karl; Kim, Hee-Yong (2014) Depletion of brain docosahexaenoic acid impairs recovery from traumatic brain injury. PLoS One 9:e86472