Omega-3 polyunsaturated fatty acid supplementation confers long-term neuroprotection against neonatal hypoxic-ischemic brain injury through anti-inflammatory actions.

Abstract

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. 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. 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-κB activation and subsequent release of inflammatory mediators. 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.