Omega-3 polyunsaturated fatty acids mitigate blood-brain barrier disruption after hypoxic-ischemic brain injury

Neurobiol Dis. 2016 Jul;91:37-46. doi: 10.1016/j.nbd.2016.02.020. Epub 2016 Feb 24.

Abstract

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been shown to protect the neonatal brain against hypoxic/ischemic (H/I) injury. However, the mechanism of n-3 PUFA-afforded neuroprotection is not well understood. One major determinant of H/I vulnerability is the permeability of the blood-brain barrier (BBB). Therefore, we examined the effects of n-3 PUFAs on BBB integrity after neonatal H/I. Female rats were fed a diet with or without n-3 PUFA enrichment from day 2 of pregnancy to 14days after parturition. H/I was introduced in 7day-old offspring. We observed relatively rapid BBB penetration of the small molecule cadaverine (640Da) at 4h post-H/I and a delayed penetration of larger dextrans (3kD-40kD) 24-48h after injury. Surprisingly, the neonatal BBB was impermeable to Evans Blue or 70kD dextran leakage for up to 48h post-H/I, despite evidence of IgG extravasation at this time. As expected, n-3 PUFAs ameliorated H/I-induced BBB damage, as shown by reductions in tracer efflux and IgG extravasation, preservation of BBB ultrastructure, and enhanced tight junction protein expression. Furthermore, n-3 PUFAs prevented the elevation in matrix metalloproteinase (MMP) activity in the brain and blood after H/I. Thus, n-3 PUFAs may protect neonates against BBB damage by blunting MMPs activation after H/I.

Keywords: Blood brain barrier; Hypoxia/ischemia; MMP-2; MMP-9; Tight junction.

MeSH terms

  • Animals
  • Animals, Newborn
  • Blood-Brain Barrier / drug effects*
  • Blood-Brain Barrier / metabolism
  • Brain / drug effects*
  • Brain / metabolism
  • Disease Models, Animal
  • Fatty Acids, Omega-3 / metabolism
  • Fatty Acids, Omega-3 / pharmacology*
  • Female
  • Hypoxia-Ischemia, Brain / drug therapy
  • Hypoxia-Ischemia, Brain / metabolism*
  • Rats, Sprague-Dawley

Substances

  • Fatty Acids, Omega-3