DHA but Not EPA Emulsions Preserve Neurological and Mitochondrial Function after Brain Hypoxia-Ischemia in Neonatal Mice
| Autor: | Zoya V. Niatsetskaya, Richard J. Deckelbaum, Iliyan Vlasakov, Hylde Zirpoli, Sergey A. Sosunov, Korapat Mayurasakorn, Vadim S. Ten, Jill J. Williams |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Mitochondrial ROS Critical Care and Emergency Medicine genetic structures lcsh:Medicine Physiology Mitochondrion Pharmacology medicine.disease_cause Biochemistry Mice Cognition Learning and Memory 0302 clinical medicine Reflexes Medicine and Health Sciences Metabolites Brain Damage lcsh:Science Energy-Producing Organelles Trauma Medicine Animal Management Hyperoxia chemistry.chemical_classification Multidisciplinary food and beverages Agriculture Mitochondria 3. Good health Neuroprotective Agents Neurology Eicosapentaenoic Acid Docosahexaenoic acid Hypoxia-Ischemia Brain Emulsions lipids (amino acids peptides and proteins) Cellular Structures and Organelles medicine.symptom Research Article Docosahexaenoic Acids Brain damage Bioenergetics Neuroprotection 03 medical and health sciences Memory medicine Animals Long-Term Memory Animal Performance Reactive oxygen species business.industry lcsh:R Biology and Life Sciences Cell Biology Mice Inbred C57BL Oxidative Stress Metabolism 030104 developmental biology chemistry Reperfusion Cognitive Science Calcium lcsh:Q Reactive Oxygen Species business 030217 neurology & neurosurgery Oxidative stress Neuroscience |
| Zdroj: | PLoS ONE, Vol 11, Iss 8, p e0160870 (2016) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0160870 |
| Popis: | Background 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. |
| Databáze: | OpenAIRE |
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