期刊
NEUROBIOLOGY OF DISEASE
卷 91, 期 -, 页码 37-46出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2016.02.020
关键词
Hypoxia/ischemia; Blood brain barrier; MMP-9; MMP-2; Tight junction
资金
- Chinese Natural Science Foundation [81020108021, 81171149, 81371306, 81571285, 81529002, 81100978, 81471332]
- Shanghai Committee of Science and Technology Support Program [14431907002]
- Young Teacher Program of Fudan University [20520131150]
- U.S. NIH [NS095671, NS36736, NS089534, NS45048]
- U.S. Department of Veterans Affairs [I01RX000420]
- American Heart Association [13SDG14570025, 15POST22260011]
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 14 days after parturition. H/I was introduced in 7 day-old offspring. We observed relatively rapid BBB penetration of the small molecule cadaverine (640 Da) at 4 h post-H/I and a delayed penetration of larger dextrans (3 kD-40 kD) 24-48 h after injury. Surprisingly, the neonatal BBB was impermeable to Evans Blue or 70 kD dextran leakage for up to 48 h 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. Published by Elsevier Inc.
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