Willis Colin L
Department of Biomedical Sciences, College of Osteopathic Medicine and Center for Excellence in the Neurosciences, University of New England, Biddeford, ME, USA.
Methods Mol Biol. 2012;814:515-29. doi: 10.1007/978-1-61779-452-0_34.
The goal of this chapter is to highlight methods used to demonstrate in vivo changes in astrocyte expression at the blood-brain barrier (BBB). Loss of BBB integrity is seen in many acute and chronic disease conditions. However, despite the importance of the BBB to homeostasis and correct functioning of the CNS, the nature of factors responsible for the induction and maintenance of BBB properties in development and the adult remains unclear. We have studied the role of astrocytes in modulating BBB integrity in two in vivo models using a gliotoxin (3-chloropropanediol), and under hypoxic stress. 3-chloropropanediol-induced astrocytic loss within the inferior colliculus leads to loss of endothelial tight junction protein expression and loss of BBB integrity. As glial fibrillary acidic protein (GFAP)-immunopositive astrocytes repopulated the lesion, tight junction protein expression returned to paracellular domains and BBB integrity was restored. Under hypoxic conditions, increased GFAP expression was seen with changes in tight junction protein expression and loss of BBB integrity. These studies suggest a critical role for glial/endothelial interactions in regulating BBB integrity in health and disease.
本章的目的是着重介绍用于证明血脑屏障（BBB）处星形胶质细胞表达的体内变化的方法。在许多急性和慢性疾病状态下均可观察到血脑屏障完整性的丧失。然而，尽管血脑屏障对中枢神经系统（CNS）的内环境稳定和正常功能至关重要，但在发育过程中和成年期负责诱导和维持血脑屏障特性的因素的性质仍不清楚。我们使用一种神经毒素（3-氯-1,2-丙二醇）并在缺氧应激条件下，在两种体内模型中研究了星形胶质细胞在调节血脑屏障完整性中的作用。3-氯-1,2-丙二醇诱导下丘内星形胶质细胞缺失，导致内皮紧密连接蛋白表达丧失和血脑屏障完整性丧失。随着胶质纤维酸性蛋白（GFAP）免疫阳性的星形胶质细胞重新填充病变部位，紧密连接蛋白表达恢复到细胞旁结构域，血脑屏障完整性得以恢复。在缺氧条件下，观察到GFAP表达增加，同时紧密连接蛋白表达发生变化，血脑屏障完整性丧失。这些研究表明，神经胶质细胞/内皮细胞相互作用在健康和疾病状态下调节血脑屏障完整性方面起着关键作用。
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