کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6021371 | 1580632 | 2016 | 10 صفحه PDF | دانلود رایگان |
- Blood brain barrier was damaged after neonatal hypoxic-ischemic (H/I) brain injury.
- nâ3 PUFA preserved the integrity of blood brain barrier following H/I.
- nâ3 PUFA alleviated degeneration of tight junction after neonatal H/I insult.
- nâ3 PUFA suppressed H/I induced activation of MMP-9 and MMP-2 both in brain and in blood.
Omega-3 polyunsaturated fatty acids (nâ3 PUFAs) have been shown to protect the neonatal brain against hypoxic/ischemic (H/I) injury. However, the mechanism of nâ3 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 nâ3 PUFAs on BBB integrity after neonatal H/I. Female rats were fed a diet with or without nâ3 PUFA enrichment from day 2 of pregnancy to 14Â days after parturition. H/I was introduced in 7Â day-old offspring. We observed relatively rapid BBB penetration of the small molecule cadaverine (640Â Da) at 4Â h post-H/I and a delayed penetration of larger dextrans (3Â kD-40Â kD) 24-48Â h after injury. Surprisingly, the neonatal BBB was impermeable to Evans Blue or 70Â kD dextran leakage for up to 48Â h post-H/I, despite evidence of IgG extravasation at this time. As expected, nâ3 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, nâ3 PUFAs prevented the elevation in matrix metalloproteinase (MMP) activity in the brain and blood after H/I. Thus, nâ3 PUFAs may protect neonates against BBB damage by blunting MMPs activation after H/I.
Journal: Neurobiology of Disease - Volume 91, July 2016, Pages 37-46