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

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Abstract

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 AT2 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 AT2 was increased on glia limitans astrocytes in PTx-treated CCL2 transgenics, whereas AT2 immunostaining was not induced in the lesion-reactive dentate gyrus. Our results suggest that AT2 induction correlates with solute leakage rather than cellular infiltration. This points to a role for AT2 in selective changes to the BBB.

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Acknowledgements

We thank Prof. Tadashi Inagami and Amita Rachakonda (Vanderbilt University, Nashville, TN, funded by NIH research grant number HL58205) for generously providing us with AT2 KO tissue. We also thank Dina Dræby for assistance with animal breeding and colony management, and Jason Millward for help with qRT-PCR.

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  1. Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, J.B. Winsloewsvej 25, 5000, Odense C, Denmark

    Laila Füchtbauer, Henrik Toft-Hansen, Reza Khorooshi & Trevor Owens

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  1. Laila Füchtbauer
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  2. Henrik Toft-Hansen
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  3. Reza Khorooshi
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  4. Trevor Owens
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Correspondence to Trevor Owens.

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The research was supported by grants to Dr. Trevor Owens from the Danish Agency for Science Technology and Innovation and from the Danish Multiple Sclerosis Society. Laila Füchtbauer was funded by a skolarstipendium from the Danish Agency for Science Technology and Innovation.

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Füchtbauer, L., Toft-Hansen, H., Khorooshi, R. et al. Expression of Astrocytic Type 2 Angiotensin Receptor in Central Nervous System Inflammation Correlates With Blood–Brain Barrier Breakdown. J Mol Neurosci 42, 89–98 (2010). https://doi.org/10.1007/s12031-010-9371-8

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