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    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; 94(8) — S. 957–966
    ISSN: 1432-1440
    Sprache
    Englisch
    Verweise
    DOI: 10.1007/s00109-016-1406-3
    Pubmed: 26983606
    Kontakt
    Institut für Tierschutz und Tierverhalten

    Königsweg 67
    Gebäude 21, 1. OG
    14163 Berlin
    Tel.: +49 30 838 62901 (Sekretariat)
    email: 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.