Expression of Astrocytic Type 2 Angiotensin Receptor in Central Nervous System Inflammation Correlates With Blood-Brain Barrier Breakdown

The blood-brain barrier (BBB), a complex of endothelial and glial barriers, controls passage of cells and solutes between the blood and central nervous system (CNS). Blood-brain barrier breakdown refers to entry of cells and/or solutes. We were interested whether the renin-angiotensin system is involved during BBB breakdown. We studied the type 2 angiotensin receptor AT(2) because of its suggested neuroprotective role. Two models of brain inflammation were used to distinguish solute versus cellular barrier functions. Both leukocytes and horseradish peroxidase (HRP) accumulated in the perivascular space of transgenic mice expressing the chemokine CCL2 in the CNS, indicating selective endothelial effects. Cellular infiltration and HRP leakage across the glia limitans to the parenchyma were induced by pertussis toxin (PTx) treatment. By contrast, there was no detectable HRP leakage in the hippocampus dentate gyrus after transection of axonal afferents, despite that leukocytes infiltrate to this site. Immunoreactivity for AT(2) was increased on glia limitans astrocytes in PTx-treated CCL2 transgenics, whereas AT(2) immunostaining was not induced in the lesion-reactive dentate gyrus. Our results suggest that AT(2) induction correlates with solute leakage rather than cellular infiltration. This points to a role for AT(2) in selective changes to the BBB.