N-3 fatty acid rich triglyceride emulsions are neuroprotective after cerebral hypoxic-ischemic injury in neonatal mice

• Published in: PloS one 2013-02, Vol.8 (2), p.e56233-e56233
• Main Authors: Williams, Jill J, Mayurasakorn, Korapat, Vannucci, Susan J, Mastropietro, Christopher, Bazan, Nicolas G, Ten, Vadim S, Deckelbaum, Richard J
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Apoptosis; Biology; Bleeding Time; Blood flow; Blood Glucose - metabolism; Brain; Brain - blood supply; Brain - drug effects; Brain - pathology; Brain - physiopathology; Brain Infarction - drug therapy; Brain Infarction - pathology; Brain Infarction - physiopathology; Brain injuries; Brain injury; Cardiovascular disease; Carotid artery; Cerebral blood flow; Cerebral infarction; Cerebrovascular Circulation - drug effects; Docosahexaenoic acid; Docosahexaenoic Acids - administration & dosage; Docosahexaenoic Acids - pharmacology; Docosahexaenoic Acids - therapeutic use; Eicosapentaenoic acid; Eicosapentaenoic Acid - administration & dosage; Eicosapentaenoic Acid - pharmacology; Eicosapentaenoic Acid - therapeutic use; Emulsions; Fatty acids; Fatty Acids, Omega-3 - administration & dosage; Fatty Acids, Omega-3 - pharmacology; Fatty Acids, Omega-3 - therapeutic use; Fatty Acids, Omega-6 - administration & dosage; Fatty Acids, Omega-6 - pharmacology; Fatty Acids, Omega-6 - therapeutic use; Fish oils; Gene expression; Head injuries; Health aspects; House mouse; Hypoxia; Hypoxia-Ischemia, Brain - drug therapy; Hypoxia-Ischemia, Brain - pathology; Hypoxia-Ischemia, Brain - physiopathology; Infarction; Injection; Injections, Intraperitoneal; Ischemia; Laboratory animals; Lipids; Medicin och hälsovetenskap; Medicine; Metabolism; Mice; Mice, Inbred C57BL; Neonates; Neuroprotection; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Newborn babies; Newborn infants; Nutrition; Omega 3 fatty acids; Oxidative stress; Pediatrics; Rodents; Spinal cord injuries; Stroke; Surgeons; Time Factors; Traumatic brain injury; Triglycerides; Triglycerides - blood; Triglycerides - pharmacology; Triglycerides - therapeutic use; Unsaturated fatty acids
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0056233

We questioned if acute administration of n-3 fatty acids (FA) carried in n-3 rich triglyceride (TG) emulsions provides neuroprotection in neonatal mice subjected to hypoxic-ischemic (H/I) brain injury. We examined specificity of FA, optimal doses, and therapeutic windows for neuroprotection after H/I. H/I insult was induced in C57BL/6J 10-day-old mice by right carotid artery ligation followed by exposure to 8% O(2) for 15 minutes at 37°C. Intraperitoneal injection with n-3-rich TG emulsions, n-6 rich TG emulsions or saline for control was administered at different time points before and/or after H/I. In separate experiments, dose responses were determined with TG containing only docosahexaenoic acid (Tri-DHA) or eicosapentaenoic acid (Tri-EPA) with a range of 0.1-0.375 g n-3 TG/kg, administered immediately after H/I insult. Infarct volume and cerebral blood flow (CBF) were measured. Treatment with n-3 TG emulsions both before- and after- H/I significantly reduced total infarct volume by a mean of 43% when administered 90 min prior to H/I and by 47% when administered immediately after H/I. In post-H/I experiments Tri-DHA, but not Tri-EPA exhibited neuroprotective effects with both low and high doses (p