Journal
STROKE
Volume 41, Issue 10, Pages 2341-2347Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/STROKEAHA.110.586081
Keywords
hypoxia/ischemia; inflammation; polyunsaturated fatty acids
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Funding
- National Institutes of Health [NS45048, NS056118, NS036736]
- Chinese Natural Science Foundation [30870794]
- Shanghai Science & Technology Bureau [08410703000]
- Chinese Ministry of Science Technology
- American Heart Association [10POST4150028]
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Background and Purpose-Current available therapies for neonatal hypoxia/ischemia (H/I) brain injury are rather limited. Here, we investigated the effect of omega-3 polyunsaturated fatty acids on brain damage and long-term neurological function after H/I in neonates. Methods-Female rats were treated with or without an omega-3 polyunsaturated fatty acids-enriched diet from the second day of pregnancy until 14 days after parturition. Seven-day-old neonates were subjected to H/I and euthanized 5 weeks later for evaluation of tissue loss. Neurological impairment was assessed progressively for 5 weeks after H/I by grid walking, foot fault, and Morris water maze. Activation of microglia and production of inflammatory mediators were examined up to 7 days after H/I. Results-Omega-3 polyunsaturated fatty acid supplementation significantly reduced brain damage and improved long-term neurological outcomes up to 5 weeks after neonatal H/I injury. Omega-3 polyunsaturated fatty acids exerted an anti-inflammatory effect in microglia both in an in vivo model of H/I and in in vitro microglial cultures subjected to inflammatory stimuli by inhibiting NF-kappa B activation and subsequent release of inflammatory mediators. Conclusions-Our results suggest that omega-3 polyunsaturated fatty acids confer potent neuroprotection against neonatal H/I brain injury through, at least partially, suppressing a microglial-mediated inflammatory response. (Stroke. 2010;41:2341-2347.)
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