Intranasal administration of vitamin D attenuates blood-brain barrier disruption through endogenous upregulation of osteopontin and activation of CD44/P-gp glycosylation signaling after subarachnoid hemorrhage in rats
Intranasal administration of vitamin D attenuates blood-brain barrier disruption through endogenous upregulation of osteopontin and activation of CD44/P-gp glycosylation signaling after subarachnoid hemorrhage in rats
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DOI：
10.1177/0271678x16671147
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发表时间：
2017-07-01
影响因子：
6.3
通讯作者：
Zhang, John H.
中科院分区：
文献类型：
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作者：
Enkhjargal, Budbazar;McBride, Devin W.;Zhang, John H.
在这项研究中，我们研究了维生素D3（VitD 3）对内源性骨桥蛋白（OPN）的作用，OPN是一种神经保护性糖蛋白，在蛛网膜下腔出血（SAH）后。采用SD大鼠蛛网膜下腔出血（SAH）模型，观察了蛛网膜下腔出血（SAH）前、后经鼻给予VitD_3（30 ng/kg）的作用。维生素D3（30、60、120 ng/kg/d）可使大鼠脑星形胶质细胞和内皮细胞内源性OPN表达增加1倍以上。维生素D3显著降低脑水肿和伊文思蓝外渗。SAH前+VitD 3组神经行为评分明显高于SAH组，SAH后+VitD 3组部分神经行为评分高于SAH组。在Pre-SAH+ VitD 3大鼠中，脑室注射转录抑制剂放线菌素D可完全减弱VitD 3的这些保护作用，并可显著抑制VitD受体和OPN的小干扰核糖核酸（siRNA）。在Pre-SAH+ VitD 3大鼠中，OPN表达显著更高，特别是A和C，但不是B，星形胶质细胞中的异构体上调，导致脑内皮细胞中的CD 44剪接和P-gp糖基化。结果显示，鼻内维生素D3通过内源性上调脑内皮细胞中的OPN和随后的CD 44和P-gp糖基化信号来减弱血脑屏障（BBB）破坏。此外，这项研究确定了一种新的战略，成本效益的管理蛛网膜下腔出血。
In this study, we investigated the role of vitamin D3 (VitD3) on endogenous osteopontin (OPN), a neuroprotective glycoprotein, after subarachnoid hemorrhage (SAH). The endovascular perforation SAH model in Sprague-Dawley rats was used to study the effect of intranasal VitD3 (30ng/kg) before (Pre-SAH+VitD3) and after (Post-SAH+VitD3) subarachnoid hemorrhage. Vitamin D3 (30, 60, 120ng/kg/day) increased more than one fold endogenous OPN expression in astrocytes and endothelial cells of rat brain. Vitamin D3 significantly decreased brain edema and Evans blue extravasation. In addition, neurobehavioral scores were significantly higher in Pre-SAH+VitD3, but partly higher in Post-SAH+VitD3, group compared with SAH group. These protective effects of vitamin D3 were completely attenuated by intracerebroventricular injection of transcription inhibitor Actinomycin D and significantly inhibited by small interfering ribonucleic acid (siRNA) for vitamin D receptor and OPN in Pre-SAH+VitD3 rats. OPN expression was significantly higher in Pre-SAH+VitD3 rats, specifically A and C, but not B, isomers were upregulated in the astrocytes, leading to CD44 splicing, and P-gp glycosylation in brain endothelial cells. The results show that intranasal vitamin D3 attenuates blood-brain barrier (BBB) disruption through endogenous upregulation of OPN and subsequent CD44 and P-gp glycosylation signals in brain endothelial cells. Furthermore, this study identifies a novel strategy for the cost-effective management of subarachnoid hemorrhage.