Adequate consumption of polyunsaturated fatty acids (PUFA) is vital for normal development and functioning of the central nervous system. The long chain n-3 PUFAs docosahexaenoic acid (DHA) and eicosapentaenoic acid are anti-inflammatory and neuroprotective in models of central nervous system injury including traumatic brain injury (TBI). During this period, we tested whether a higher brain DHA status in a mouse model on an adequate dietary alpha-linolenic acid (ALA) leads to reduced neuroinflammation and improved spontaneous recovery after TBI in comparison to a moderately lowered brain DHA status that can occur in humans. Mice reared on diets with differing alpha-linolenic acid content were injured by a single cortical contusion impact. Change in the expression of inflammatory cytokines was measured and cellular changes occurring after injury were analyzed by immunostaining for macrophage/microglia and astrocytes. Behavioral studies included rotarod and beam walk tests and contextual fear conditioning. Marginal supply (0.04%) of ALA as the sole dietary source of n-3 PUFA from early gestation produced reduction of brain DHA by 35% in adult offspring mice in comparison to the mice on adequate ALA diet (3.1%). The DHA-depleted group showed significantly increased TBI-induced expression of pro-inflammatory cytokines TNF-alpha, IL-1beta and IL-6 in the brain as well as slower functional recovery from motor deficits compared to the adequate ALA group. Despite the reduction of pro-inflammatory cytokine expression, adequate ALA diet did not significantly alter either microglia/macrophage density around the contusion site or the relative M1/M2 phenotype. However, the glial fibrillary acidic protein immunoreactivity was reduced in the injured cerebral cortex of the mice on adequate ALA diet, indicating that astrocyte activation may have contributed to the observed differences in cellular and behavioral responses to TBI. In conclusion, increasing the brain DHA level even from a moderately DHA-depleted state can reduce neuroinflammation and improve functional recovery after TBI, suggesting possible improvement of functional outcome by increasing dietary n-3 PUFA in human TBI. During this period, we also established an animal TBI model that resembles human repeated mild TBI using The Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA) to investigate long-term neuropathological and cognitive functional consequences of repeated head injury.
|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|