Fachbereich Veterinärmedizin



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

    Zeitschriftenartikel / wissenschaftlicher Beitrag
    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
    Journal of molecular medicine; 94(8) — S. 957–966
    ISSN: 1432-1440
    DOI: 10.1007/s00109-016-1406-3
    Pubmed: 26983606
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    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.