title: N-3 fatty acid rich triglyceride emulsions are neuroprotective after cerebral hypoxic-ischemic injury in neonatal mice.
abstract: 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<0.05). Moreover, delayed post-H/I treatment with Tri-DHA significantly decreased total infarct volume by a mean of 51% when administered at 0 hr, by 46% at 1 hr, and by 51% at 2 hr after H/I insult. No protective effect occurred with Tri-DHA injection at 4 hr after H/I. There were no n-3 TG related differences in CBF. A significant reduction in brain tissue death was maintained after Tri-DHA injection at 8 wk after the initial brain injury. Thus, n-3 TG, specifically containing DHA, is protective against H/I induced brain infarction when administered up to 2 hr after H/I injury. Acute administration of TG-rich DHA may prove effective for treatment of stroke in humans.
authors: Institute of Human Nutrition, Department of Pediatrics, College of Physicians and Surgeons of Columbia University, New York, New York, USA.
authors: Jill J
authors: JJ
authors: Williams
authors: Korapat
authors: K
authors: Mayurasakorn
authors: Susan J
authors: SJ
authors: Vannucci
authors: Christopher
authors: C
authors: Mastropietro
authors: Nicolas G
authors: NG
authors: Bazan
authors: Vadim S
authors: VS
authors: Ten
authors: Richard J
authors: RJ
authors: Deckelbaum
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001760:Bleeding Time; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D020520:Brain Infarction / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004655:Emulsions; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D043371:Fatty Acids, Omega-6 / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D014280:Triglycerides / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D004655:Emulsions; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D018696:Neuroprotective Agents; D014280:Triglycerides; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid