Non-invasive vagus nerve stimulation reduces blood-brain barrier disruption in a rat model of ischemic stroke.
Non-invasive vagus nerve stimulation reduces blood-brain barrier disruption in a rat model of ischemic stroke.
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DOI：
10.1016/j.brs.2018.01.034
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发表时间：
2018-07
影响因子：
7.7
通讯作者：
Yang Y
中科院分区：
文献类型：
--
作者：
Yang Y;Yang LY;Orban L;Cuylear D;Thompson J;Simon B;Yang Y
迷走神经刺激（VNS）可显著减少脑缺血大鼠模型的梗死体积，但这种保护作用的机制尚不清楚。本研究验证了以下假设：在短暂性大脑中动脉闭塞（MCAO）期间，非侵入性VNS（nVNS）保护血脑屏障（BBB），从而减少缺血脑中的梗死面积。自发性高血压大鼠（SHR）进行了90分钟的MCAO。nVNS治疗的大鼠在MCAO发作后30分钟开始在颈部覆盖颈迷走神经的皮肤上接受5次刺激（持续时间：2分钟;每10分钟一次）。对照组大鼠接受相同的刺激股四头肌。在MCAO发作后24小时，进行MRI和免疫组织化学（IHC）分析梗死面积和BBB渗漏。与对照组相比，解剖MRI T2加权图像显示nVNS组的梗死面积明显较小。动态对比增强（DCE）-MRI显示nVNS组病变区BBB转移率（Ki图）显著降低，这与梗死面积的衰减在空间上相关。此外，在nVNS治疗的大鼠中，在缺血半球中观察到通过IHC可视化的显著较低的血清IgG渗漏。nVNS还保护微血管中的血管紧密连接蛋白免受破坏，并减少缺血半球中受损血管周围的反应性星形胶质细胞中基质金属蛋白酶-2/9的表达。我们的数据表明，在MCA闭塞期间一系列nVNS给药的神经保护作用，在空间上与保护BBB完整性免受损伤和减少缺血性卒中引起的梗死范围相关。
Vagus nerve stimulation (VNS) significantly reduces infarct volume in rat models of cerebral ischemia, but the mechanism of this protective effect remains open. This study tested the hypothesis that non-invasive VNS (nVNS), during transient middle cerebral artery occlusion (MCAO), protects the blood-brain barrier (BBB), leading to reduced infarct size in ischemic brain. Spontaneous hypertensive rats (SHRs) were subjected to a 90 min MCAO. nVNS treated rats received 5 stimulations (duration: 2min; every 10 min) on the skin overlying the cervical vagus nerve in the neck beginning 30 min after MCAO onset. Control rats received the same stimulations on the quadriceps femoris muscle. Twenty-four hours after MCAO onset, MRI and immunohistochemistry (IHC) were performed for analyses of infarct size and BBB leakage. Compared with the control group, anatomic MRI T2-weighted images showed significantly smaller infarct sizes in the nVNS group. Dynamic contrast-enhanced (DCE)-MRI showed a significantly decreased BBB transfer rate (Ki map) in the lesion area in the nVNS group, which was spatially correlated with the attenuation of the infarct size. Furthermore, significantly lower serum IgG leakage, visualized by IHC, was seen in the ischemic hemisphere in nVNS treated rats. nVNS also protected vascular tight junction proteins from disruption in microvessels, and reduced expression of matrix metalloproteinases-2/9 in reactive astrocytes surrounding the compromised vessels in the ischemic hemispheres. Our data suggest that the neuroprotective role of a series of nVNS administrations during MCA occlusion, spatially correlates with protection of BBB integrity from damage and reduction of infarct extent induced by ischemic stroke.
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影响因子：
5.1
作者：
Ben-Menachem E;Revesz D;Simon BJ;Silberstein S
通讯作者：
Silberstein S
缺血性中风中的迷走神经刺激：新瓶中的旧酒。
影响因子：
3.4
作者：
Cai PY;Bodhit A;Derequito R;Ansari S;Abukhalil F;Thenkabail S;Ganji S;Saravanapavan P;Shekar CC;Bidari S;Waters MF;Hedna VS
通讯作者：
Hedna VS
影响因子：
6.3
作者：
Krueger, Martin;Bechmann, Ingo;Michalski, Dominik
通讯作者：
Michalski, Dominik
影响因子：
8.3
作者：
Fisher M;Feuerstein G;Howells DW;Hurn PD;Kent TA;Savitz SI;Lo EH;STAIR Group
通讯作者：
STAIR Group
影响因子：
34.7
作者：
Neuwelt, Edward A.;Bauer, Bjoern;Fahlke, Christoph;Fricker, Gert;Iadecola, Constantino;Janigro, Damir;Leybaert, Luc;Molnar, Zoltan;O'Donnell, Martha E.;Povlishock, John T.;Saunders, Norman R.;Sharp, Frank;Stanimirovic, Danica;Watts, Ryan J.;Drewes, Lester R.
通讯作者：
Drewes, Lester R.