Rapôso Catarina, Zago Gabriela Mariotoni, da Silva Gustavo Henrique, da Cruz Höfling Maria Alice
Departamento de Histologia e Embriologia, Instituto de Biologia, C.P. 6109, Universidade Estadual de Campinas, Campinas, SP, 13083-970, Brazil.
Brain Res. 2007 May 29;1149:18-29. doi: 10.1016/j.brainres.2007.02.086. Epub 2007 Mar 7.
A highly controlled transport of substances at the interface between blood and brain characterizes the blood-brain barrier (BBB), fundamental for maintenance of the homeostasis of the cerebral milieu. In this study, we investigated the time course (15 min, 1, 2, and 5 h) of BBB opening induced by intravenous (i.v.) injection of Phoneutria nigriventer spider venom (PNV) using quantitative and morphological approaches on cerebellum and hippocampus vessels for assessment of BBB permeability. The results showed vasogenic edema and tracer extravasation faster and severalfold higher in hippocampus than in cerebellum. Reactive astrocytes with swollen perivascular end-feet processes were found only in cerebellum. An immediate and total degradation of laminin in capillaries occurred resulting in the disappearance of the basement membrane. In medium-sized vessels, this effect was less prominent. The changes were transient, with cerebellum in general presenting a faster recovery. However, at 5 h laminin was overexpressed, principally in hippocampus. The rapid and abrupt shift of laminin expression in capillaries (at 15 min) coincided with the immediate and severe signs of intoxication shown by the animals, but not with the peak of leakage of vessels and vasogenic edema, which occurred later (1-2 h). The findings suggest a complex regulatory mechanism, since the extension of BBB impairment caused by PNV depends on the region of the SNC, and on the vessels types. It is suggested that the components of the BBB (gliovascular unit) have a critical role in these differences. P. nigriventer venom can be a useful tool to explore the mechanisms of BBB.
血液与脑之间界面处物质的高度受控运输是血脑屏障（BBB）的特征，这对于维持脑内环境的稳态至关重要。在本研究中，我们采用定量和形态学方法，对小脑和海马体血管进行评估，以研究静脉注射黑腹捕鸟蛛毒液（PNV）诱导血脑屏障开放的时间进程（15分钟、1小时、2小时和5小时），从而评估血脑屏障的通透性。结果显示，海马体中的血管源性水肿和示踪剂外渗比小脑更快且高出数倍。仅在小脑中发现了具有肿胀的血管周围终足突起的反应性星形胶质细胞。毛细血管中的层粘连蛋白立即完全降解，导致基底膜消失。在中等大小的血管中，这种效应不太明显。这些变化是短暂的，总体而言小脑恢复得更快。然而，在5小时时，层粘连蛋白过度表达，主要在海马体中。毛细血管中层粘连蛋白表达的快速而突然的变化（在15分钟时）与动物出现的立即且严重的中毒迹象相符，但与血管渗漏和血管源性水肿的峰值不一致，后者出现得更晚（1 - 2小时）。这些发现提示了一种复杂的调节机制，因为PNV引起的血脑屏障损伤程度取决于中枢神经系统的区域以及血管类型。提示血脑屏障的组成部分（神经胶质血管单元）在这些差异中起关键作用。黑腹捕鸟蛛毒液可能是探索血脑屏障机制的有用工具。
