Evidence for differential changes of junctional complex proteins in murine neurocysticercosis dependent upon CNS vasculature
Evidence for differential changes of junctional complex proteins in murine neurocysticercosis dependent upon CNS vasculature
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DOI：
10.1016/j.brainres.2007.07.010
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发表时间：
2007-09-12
期刊：
影响因子：
2.9
通讯作者：
Teale, Judy M.
中科院分区：
文献类型：
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作者：
Alvarez, Jorge I.;Teale, Judy M.
维持中枢神经系统 (CNS) 稳态所需的微妙平衡由血脑屏障 (BBB) 控制。受伤后，血脑屏障会受到破坏，从而损害中枢神经系统。 BBB 破坏被表示为统一事件。然而，我们的小组在神经囊尾蚴病 (NCC) 小鼠模型中表明，血脑屏障破坏因分析的解剖部位/血管床而异。在这项研究中，通过检测感染了皮质中绦虫的小鼠大脑中连接复合蛋白的表达，进一步了解了位于软脑膜（软脑膜血管）和脑实质（实质血管）的血管中血脑屏障破坏的机制。来自模拟感染动物的软脑膜和实质血管均表现出显着的连接蛋白共定位，并表现出有组织的结构。感染后，图案化组织被破坏，在某些情况下，特定的紧密连接和粘附连接蛋白无法检测到或似乎正在进行蛋白水解。两种类型的血管之间这些变化的程度和时间有所不同（软脑膜血管在几天内破裂，而实质血管则在几周内破裂）。为了探究潜在机制，通过原位酶谱法评估了基质金属蛋白酶 9 (MMP-9) 的表达和活性。结果表明，BBB 破坏部位的 MMP-9 活性增加，表现出白细胞浸润。此外，软脑膜和实质血管中 MMP 活性的时间与渗透性破坏的时间相关。于是，崩溃。尽管软脑膜和实质血管之间的连接复合体具有相似的结构并且涉及 MMP 活性，但 BBB 的形成是一个可变的过程。 (C) 2007 Elsevier B.V. 保留所有权利。
The delicate balance required to maintain homeostasis of the central nervous system (CNS) is controlled by the blood-brain barrier (BBB). Upon injury, the BBB is disrupted compromising the CNS. BBB disruption has been represented as a uniform event. However, our group has shown in a murine model of neurocysticercosis (NCC) that BBB disruption varies depending upon the anatomical site/vascular bed analyzed. In this study further understanding of the mechanisms of BBB disruption was explored in blood vessels located in leptomeninges (pial vessels) and brain parenchyma (parenchymal vessels) by examining the expression of junctional complex proteins in murine brain infected with Mesocestoides corti. Both pial and parenchymal vessels from mock infected animals showed significant colocalization of junctional proteins and displayed an organized architecture. Upon infection, the patterned organization was disrupted and in some cases, particular tight junction and adherens junction proteins were undetectable or appeared to be undergoing proteolysis. The extent and timing of these changes differed between both types of vessels (pial vessel disruption within days versus weeks for parenchymal vessels). To approach potential mechanisms, the expression and activity of matrix metalloproteinase-9 (MMP-9) were evaluated by in situ zymography. The results indicated an increase in MMP-9 activity at sites of BBB disruption exhibiting leukocyte infiltration. Moreover, the timing of MMP activity in pial and parenchymal vessels correlated with the timing of permeability disruption. Thus, breakdown. of the BBB is a mutable process despite the similar structure of the junctional complex between pial and parenchymal vessels and involvement of MMP activity. (C) 2007 Elsevier B.V. All rights reserved.