Transcellular transport as a mechanism of blood-brain barrier disruption during stroke
Transcellular transport as a mechanism of blood-brain barrier disruption during stroke
复制标题
DOI：
10.2741/1282
复制
发表时间：
2004-01-01
影响因子：
3.1
通讯作者：
Rix, RD
中科院分区：
文献类型：
--
作者：
Cipolla, MJ;Crete, R;Rix, RD
众所周知，缺血引起血脑屏障(BBB)的破坏，从而导致血管源性脑水肿的形成。血脑屏障开放的一个主要机制是促进吞噬细胞囊泡的形成，这可能是由几种机制引起的，包括一氧化氮的产生、神经递质的释放、炎症介质和血流动力学的改变。在本研究中，我们试图描述脑缺血/再灌流(I/R)和血管内压升高期间脑内皮细胞吞噬的程度。采用Wistar雄性大鼠大脑中动脉(MCAS)微丝闭塞模型，造成1h再灌注2 4h的短暂性局灶性脑缺血模型，然后在动脉造影室中将闭塞的大脑中动脉(MCAS)解剖固定在玻璃套管上。这个系统可以控制血管内压，测量管腔直径，并用各种示踪剂(荧光黄和辣根过氧化物酶)灌流，以测量跨细胞转运，并使用透射电子显微镜定量胞饮作用。与75 mm Hg的非缺血对照MCAS相比，I/R可使基底侧小泡形成增加166%，顶端小泡形成没有改变(p<；0.01)。同样，当压力急剧升高至200毫米汞柱时，心尖部吞噬作用增加78%(p<；0.05)，而基底部增加42%，并不显著。这些结果得到了使用荧光黄的通透性测量的证实，并表明I/R和血管内压的急性升高都增强了脑内皮细胞的吞噬作用。缺血时基底外侧吞饮作用的增加表明外流机制增强，可能是将物质从大脑输送到血液。此外，由于体外分离的动脉在加压后吞饮作用增强，不受代谢或神经因素的影响，这些发现表明血管内压升高是脑血管内皮细胞吞饮作用的主要刺激因素。
It is well-known that ischemia causes disruption of the blood-brain barrier (BBB), which leads to the formation of vasogenic brain edema. One major mechanism of BBB opening is enhanced pinocytotic vesicle formation that may be induced after transient focal ischemia by several mechanisms, including nitric oxide production, release of neurotransmitters, inflammatory mediators and hemodynamic alterations. In the present study we sought to characterize the extent of pinocytosis in cerebral endothelium during both ischemia/reperfusion (I/R) and elevated intravascular pressure. Transient focal ischemia was induced for 1 hour with 24 hours of reperfusion using the filament occlusion model in male Wistar rats, after which occluded middle cerebral arteries (MCAs) were dissected and mounted on glass cannulas in an arteriograph chamber. This system allowed control over intravascular pressure, measurement of lumen diameter and perfusion with various tracers (Lucifer Yellow and horseradish peroxidase) for measurement of transcellular transport and quantification of pinocytosis using transmission electron microscopy. I/R was found to increase vesicle formation by 166% basolaterally without a change in vesicle formation apically compared to non-ischemic control MCAs at 75 mmHg (p < 0.01). Similarly, an acute increase in pressure to 200 mmHg caused a 78% increase in apical pinocytosis (p < 0.05) and a non-significant 42% increase basolaterally. These results were confirmed by permeability measurements using Lucifer Yellow and demonstrate that both I/R and acute elevations in intravascular pressure enhance cerebral endothelial cell pinocytosis. The increase in basolateral pinocytosis during ischemia suggests enhanced efflux mechanisms that may be transporting substances from brain to blood. In addition, since the enhanced pinocytosis after an increase in pressure occurred in isolated arteries in vitro without the influence of metabolic or neuronal factors, these findings demonstrate that elevated intravascular pressure is a primary stimulus for pinocytosis in cerebral endothelial cells.