Omega-3 polyunsaturated fatty acid supplementation confers long-term neuroprotection against neonatal hypoxic-ischemic brain injury through anti-inflammatory actions.
OBJECTIVE
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-κB 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.
Zhang
Wenting
W
Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. chenj2@upmc.edu
Hu
Xiaoming
X
Yang
Wei
W
Gao
Yanqin
Y
Chen
Jun
J
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008431:Maternal-Fetal Exchange; D018782:Maze Learning / Q000187:drug effects; D017628:Microglia / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013995:Time
D015525:Fatty Acids, Omega-3; D018696:Neuroprotective Agents