创伤性脑损伤的神经复原力:参与神经保护和恢复的二十二碳六酸生物活性代谢产物鉴定
Neural Resilience to Traumatic Brain Injury: Identification of Bioactive Metabolites of Docosahexaenoic Acids Involved in Neuroprotection and Recovery
关键词:创伤性脑损伤;酸;解剖模型;生物化学
摘 要:A mouse model of TBI has been established with behavioral test parameters to evaluate functional deficits. Dietary conditions to generate extreme and moderate n-3 fatty acid depletion in the mouse brain have been established for testing TBI outcome. Significant retardation of spontaneous recovery from TBI-induced motor and cognitive deficits in mice raised on an n-3 deficient diet where brain DHA was depleted by over 70%. Degradation of alpha spectrin, a marker of TBI induced injury, was elevated in the cortex of TBI- inflicted DHA-deficient mice with less NeuN-positive neurons, indicating exacerbated injury in these animals. Moderate depletion of DHA (by 30%) also showed the same trend in behavioral outcome, and biochemical characterization is in progress. Effects of DHA and synaptamide on axon growth have been established in cortical neuron cultures. Software for the isotope assisted mass spectrometric identification of metabolites has been developed which is being applied to DHA-derived metabolites formed by cortical neurons in cultures as well as TBI-inflicted brain homogenates. A nanosymposia presentation and a manuscript have been generated from this project.