Imaging in vivo astrocyte/endothelial cell interactions at the blood-brain barrier

Abstract

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.