N-3 Fatty Acid Rich Triglyceride Emulsions Are Neuroprotective after Cerebral Hypoxic-Ischemic Injury in Neonatal MiceReportar como inadecuado

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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% O2 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.

Autor: Jill J. Williams , Korapat Mayurasakorn , Susan J. Vannucci, Christopher Mastropietro, Nicolas G. Bazan, Vadim S. Ten, Richard J.

Fuente: http://plos.srce.hr/


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