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Angiotensin AT2-receptor stimulation improves survival and neurological outcome after experimental stroke in mice
Charite, Fac Med, Ctr Cardiovasc Res, Berlin, Germany..
Maastricht Univ, CARIM, Maastricht, Netherlands..
Charite, Fac Med, Ctr Cardiovasc Res, Berlin, Germany..
Univ Southern Denmark, Inst Mol Med, Dept Neurobiol, Odense, Denmark..
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2016 (English)In: Journal of Molecular Medicine, ISSN 0946-2716, E-ISSN 1432-1440, Vol. 94, no 8, 957-966 p.Article in journal (Refereed) Published
Abstract [en]

This study investigated the effect of post-stroke, direct AT2-receptor (AT2R) stimulation with the non-peptide AT2R-agonist compound 21 (C21) on infarct size, survival and neurological outcome after middle cerebral artery occlusion (MCAO) in mice and looked for potential underlying mechanisms. C57/BL6J or AT2R-knockout mice (AT2-KO) underwent MCAO for 30 min followed by reperfusion. Starting 45 min after MCAO, mice were treated once daily for 4 days with either vehicle or C21 (0.03 mg/kg ip). Neurological deficits were scored daily. Infarct volumes were measured 96 h post-stroke by MRI. C21 significantly improved survival after MCAO when compared to vehicle-treated mice. C21 treatment had no impact on infarct size, but significantly attenuated neurological deficits. Expression of brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB) (receptor for BDNF) and growth-associated protein 43 (GAP-43) were significantly increased in the peri-infarct cortex of C21-treated mice when compared to vehicle-treated mice. Furthermore, the number of apoptotic neurons was significantly decreased in the peri-infarct cortex in mice treated with C21 compared to controls. There were no effects of C21 on neurological outcome, infarct size and expression of BDNF or GAP-43 in AT2-KO mice. From these data, it can be concluded that AT2R stimulation attenuates early mortality and neurological deficits after experimental stroke through neuroprotective mechanisms in an AT2R-specific way.

Place, publisher, year, edition, pages
2016. Vol. 94, no 8, 957-966 p.
Keyword [en]
MCAO, AT2-receptor, Stroke, Renin-angiotensin system, Neuroprotection
National Category
Medical Genetics
Identifiers
URN: urn:nbn:se:uu:diva-308249DOI: 10.1007/s00109-016-1406-3ISI: 000380233700011PubMedID: 26983606OAI: oai:DiVA.org:uu-308249DiVA: diva2:1049449
Available from: 2016-11-24 Created: 2016-11-24 Last updated: 2016-11-24Bibliographically approved

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