Omega-3 polyunsaturated fatty acids mitigate blood-brain barrier disruption after hypoxic-ischemic brain injury.
Omega-3 polyunsaturated fatty acids mitigate blood-brain barrier disruption after hypoxic-ischemic brain injury.
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Omega-3 多不饱和脂肪酸可减轻缺氧缺血性脑损伤后血脑屏障的破坏
DOI：
10.1016/j.nbd.2016.02.020
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发表时间：
2016-07
影响因子：
6.1
通讯作者：
Gao Y
中科院分区：
文献类型：
--
作者：
Zhang W;Zhang H;Mu H;Zhu W;Jiang X;Hu X;Shi Y;Leak RK;Dong Q;Chen J;Gao Y
Omega-3多不饱和脂肪酸（n-3 PUFA）已被证明可以保护新生儿大脑免受缺氧/缺血（H/I）损伤。然而，n-3 PUFA提供的神经保护的机制还没有很好地理解。H/I脆弱性的一个主要决定因素是血脑屏障（BBB）的渗透性。因此，我们研究了新生儿H/I后n-3 PUFAs对BBB完整性的影响。雌性大鼠从妊娠第2天至分娩后14天喂食含或不含n-3 PUFA富集的饮食。在7日龄的子代中引入H/I。小分子尸胺（640 Da）在伤后4 h进入血脑屏障较快，大分子葡聚糖（3 kD-40 kD）在伤后24- 48 h进入血脑屏障延迟。令人惊讶的是，新生儿BBB在H/I后长达48小时内对伊文思蓝或70 kD葡聚糖渗漏是不可渗透的，尽管此时有IgG外渗的证据。正如预期的那样，n-3 PUFAs改善H/I诱导的BBB损伤，如示踪剂流出和IgG外渗减少，BBB超微结构的保存和紧密连接蛋白表达增强所示。此外，n-3 PUFAs防止H/I后脑和血液中基质金属蛋白酶（MMP）活性的升高。因此，n-3 PUFAs可能通过钝化H/I后MMPs的活化来保护新生儿免受BBB损伤。
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 (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.