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

NEUROBIOLOGY OF DISEASE

卷:91

Article

Zhang, Wenting^1,3,4  Zhang, Hui^1,2  Mu, Hongfeng¹  Zhu, Wen^3,4  Jiang, Xiaoyan^1,3,4  Hu, Xiaoming^1,3,4  Shi, Yejie^3,4  Leak, Rehana K.⁵  Dong, Qiang^1,2  Chen, Jun^1,3,4,6  Gao, Yanqin^1,3,4 

[1] Fudan Univ, Inst Brain Sci, Collaborat Innovat Ctr Brain Sci, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China

[2] Fudan Univ, Dept Neurol, Huashan Hosp, Shanghai 200032, Peoples R China

[3] Univ Pittsburgh, Sch Med, Ctr Cerebrovasc Dis, Pittsburgh, PA 15213 USA

[4] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA

[5] Duquesne Univ, Div Pharmaceut Sci, Mylan Sch Pharm, Pittsburgh, PA 15282 USA

[6] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15261 USA

关键词: Hypoxia/ischemia;    Blood brain barrier;    MMP-9;    MMP-2;    Tight junction;   

DOI  :  10.1016/j.nbd.2016.02.020

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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