Mayurasakorn, KorapatNiatsetskaya, Zoya V.Sosunov, Sergey A.Williams, Jill J.Zirpoli, HyldeVlasakov, IliyanDeckelbaum, Richard J.Ten, Vadim S.2016-10-112016Mayurasakorn, Korapat, Zoya V. Niatsetskaya, Sergey A. Sosunov, Jill J. Williams, Hylde Zirpoli, Iliyan Vlasakov, Richard J. Deckelbaum, and Vadim S. Ten. 2016. “DHA but Not EPA Emulsions Preserve Neurological and Mitochondrial Function after Brain Hypoxia-Ischemia in Neonatal Mice.” PLoS ONE 11 (8): e0160870. doi:10.1371/journal.pone.0160870. http://dx.doi.org/10.1371/journal.pone.0160870.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:29002536Background and Purpose Treatment with triglyceride emulsions of docosahexaenoic acid (tri-DHA) protected neonatal mice against hypoxia-ischemia (HI) brain injury. The mechanism of this neuroprotection remains unclear. We hypothesized that administration of tri-DHA enriches HI-brains with DHA/DHA metabolites. This reduces Ca2+-induced mitochondrial membrane permeabilization and attenuates brain injury. Methods: 10-day-old C57BL/6J mice following HI-brain injury received tri-DHA, tri-EPA or vehicle. At 4–5 hours of reperfusion, mitochondrial fatty acid composition and Ca2+ buffering capacity were analyzed. At 24 hours and at 8–9 weeks of recovery, oxidative injury, neurofunctional and neuropathological outcomes were evaluated. In vitro, hyperoxia-induced mitochondrial generation of reactive oxygen species (ROS) and Ca2+ buffering capacity were measured in the presence or absence of DHA or EPA. Results: Only post-treatment with tri-DHA reduced oxidative damage and improved short- and long-term neurological outcomes. This was associated with increased content of DHA in brain mitochondria and DHA-derived bioactive metabolites in cerebral tissue. After tri-DHA administration HI mitochondria were resistant to Ca2+-induced membrane permeabilization. In vitro, hyperoxia increased mitochondrial ROS production and reduced Ca2+ buffering capacity; DHA, but not EPA, significantly attenuated these effects of hyperoxia. Conclusions: Post-treatment with tri-DHA resulted in significant accumulation of DHA and DHA derived bioactive metabolites in the HI-brain. This was associated with improved mitochondrial tolerance to Ca2+-induced permeabilization, reduced oxidative brain injury and permanent neuroprotection. Interaction of DHA with mitochondria alters ROS release and improves Ca2+ buffering capacity. This may account for neuroprotective action of post-HI administration of tri-DHA.en-USBiology and Life SciencesBiochemistryBioenergeticsEnergy-Producing OrganellesMitochondriaCell BiologyCellular Structures and OrganellesMedicine and Health SciencesNeurologyBrain DamageCritical Care and Emergency MedicineTrauma MedicineMetabolismMetabolitesReperfusionAgricultureAnimal ManagementAnimal PerformanceNeuroscienceReflexesCognitive ScienceCognitionMemoryLong-Term MemoryLearning and MemoryJournal Article2016-10-1110.1371/journal.pone.0160870