Neural Resilience to Traumatic Brain Injury: Identification of Bioactive Metabolites of Docosahexaenoic Acids Involved in Neuroprotection and Recovery.

摘要

Using a mouse model of TBI that was established in our lab, we demonstrated that extreme n-3 fatty acid depletion in the mouse brain exacerbates TBI outcome for which a scientific publication in PLoS One was generated. Moderate depletion of DHA (by 30%) in the brain also showed the same trend; TBI-inflicted DHA-deficient mice exhibited slower functional recovery and their brains showed more degradation of alpha spectrin. Both male and female mice were similarly affected by the DHA-depletion. An in vitro model to evaluate axon regeneration after injury has been established using cortical neuron cultures. Using this model we demonstrated the induction of axonal regrowth by synaptamide, a bioactive metabolite of DHA. Using quantitative mass spectrometry, the time course of bioactive metabolite production in TBI-inflicted brain was determined. We identified three distinctive groups of metabolites according to the peak time of production after injury. The synaptamide level was steadily increased after TBI. DHA administration protocol is being optimized for the formation of active metabolites such as synaptamide as well as functional recovery outcome after TBI.