Publication Database

Angiotensin AT2-receptor stimulation improves survival and neurological outcome after experimental stroke in mice (2016)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Schwengel, Katja

Namsolleck, Pawel

Lucht, Kristin

Clausen, Bettina H.

Lambertsen, Kate L.

Valero-Esquitino, Veronica

Thöne-Reineke, Christa (WE 11)

Müller, Susanne

Widdop, Robert E.

Denton, Kate M.

Horiuchi, Masatsugu

Iwai, Masaru

Boato, Francesco

Dahlöf, Björn

Hallberg, Anders

Unger, Thomas

Steckelings, U. Muscha

Quelle

Journal of molecular medicine

Bandzählung: 94

Heftzählung: 8

Seiten: 957 – 966

ISSN: 1432-1440

Sprache

Englisch

Verweise

DOI: 10.1007/s00109-016-1406-3

Pubmed: 26983606

Kontakt

Institut für Tierschutz, Tierverhalten und Versuchstierkunde

Königsweg 67
14163 Berlin
+49 30 838 61146
tierschutz@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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. Key message • AT2R stimulation after MCAO in mice reduces mortality and neurological deficits.• AT2R stimulation increases BDNF synthesis and protects neurons from apoptosis.• The AT2R-agonist C21 acts protectively when applied post-stroke and peripherally.