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Abstract

Background:

Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing inflammatory central nervous system (CNS) disease for which there is no cure. Immunoglobulin G autoantibodies specific for the water channel aquaporin-4 are a serum biomarker, believed to induce complement-dependent astrocyte damage with secondary demyelination.

Objective:

To investigate the effect of angiotensin AT2 receptor (AT2R) stimulation on NMOSD-like pathology and its underlying mechanism.

Methods:

NMOSD-like pathology was induced in mice by intracerebral injection of immunoglobulin-G isolated from NMOSD patient serum, with complement. This mouse model produces the characteristic histological features of NMOSD. A specific AT2R agonist, Compound 21 (C21), was given intracerebrally at day 0 and by intrathecal injection at day 2.

Results:

Loss of aquaporin-4 and glial fibrillary acidic protein was attenuated by treatment with C21. Administration of C21 induced mRNA for interleukin-10 in the brain. NMOSD-like pathology was exacerbated in interleukin-10-deficient mice, suggesting a protective role. C21 treatment did not attenuate NMOSD-like pathology in interleukin-10-deficient mice, indicating that the protective effect of AT2R stimulation was dependent on interleukin-10.

Conclusion:

Our findings identify AT2R as a novel potential therapeutic target for the treatment of NMOSD. Interleukin-10 signaling is an essential part of the protective mechanism counteracting NMOSD pathology.

Keywords

Neuromyelitis optica spectrum disorder angiotensin AT2 receptor astrocytopathology IL-10 Compound 21

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Angiotensin AT2 receptor–induced interleukin-10 attenuates neuromyelitis optica spectrum disorder–like pathology

Abstract

Background:

Objective:

Methods:

Results:

Conclusion:

Keywords

Get full access to this article

References

Supplementary Material