cad a22 4500 551414707 20191007042150.0 cr unu---uuuuu 181214e20190301xx s 000 0 eng 10.5167/uzh-159386 doi 10.1093/cvr/cvy248 doi (ZORA)oai:www.zora.uzh.ch:159386 610 ddc 30295757 pmid Contraceptive drugs mitigate experimental stroke-induced brain injury [Elektronische Daten] [Mohamad El Amki, Nadine Binder, Riccardo Steffen, Hannah Schneider, Andreas R Luft, Michael Weller, Bruno Imthurn, Gabriele S Merki-Feld, Susanne Wegener] openAccess eu-repo Aims: Effective stroke treatments beyond reperfusion remain scant. The natural steroid hormone progesterone has shown protective effects in experimental models of brain injury and cardiovascular disease. However, unfavorable bioavailability limits its clinical use. Desogestrel and drospirenone are new generation progestins with progesterone-like properties, developed as oral contraceptives with excellent bioavailability and safety profile. We investigated the neuroprotective properties of these progestins in vivo using transient middle cerebral artery occlusion (MCAO) and in vitro using an oxygen-glucose deprivation and reoxygenation (OGD/R) model in primary neuronal cells. Methods and Results: MCAO was induced in female, female ovariectomized (modeling postmenopausal females) and male mice. Treatment with the progestins resulted in less severe strokes after MCAO and less neuronal death in OGD/R. Desogestrel and drospirenone induced higher expression levels of GABAAR α4 and delta subunits within the brain, suggesting changes in GABAAR configuration favoring tonic inhibition as potential mechanism of action. Treatment with the GABAAR blocker picrotoxin abolished the protection afforded by the progestins in vivo and in vitro. Conclusions: For the first time, here we delineate a potential role of desogestrel and drospirenone, both clinically approved and safe drugs in mitigating the consequences of stroke. Contraception with desogestrel and drospirenone in progestin-only preparations may be particularly beneficial for women at risk of stroke. Clinic for Neurology zora Neuroscience Center Zurich zora Clinic for Reproductive Endocrinology zora Physiology (medical), Physiology, Cardiology and Cardiovascular Medicine zora El Amki Mohamad joint author Binder Nadine joint author Steffen Riccardo joint author Schneider Hannah joint author Luft Andreas R. joint author Weller Michael joint author Imthurn Bruno joint author Merki-Feld Gabriele S. joint author Wegener Susanne joint author Cardiovascular Research 115(3):637-646 https://www.zora.uzh.ch/id/eprint/159386/3/Resub_Elamki_wegener_CVR_August27.pdf text/html WWW-Backlink auf das Repository 1 Journal Article PeerReviewed zora ZORA 856 40 https://www.zora.uzh.ch/id/eprint/159386/3/Resub_Elamki_wegener_CVR_August27.pdf text/html WWW-Backlink auf das Repository ZORA 700 1- El Amki Mohamad joint author ZORA 700 1- Binder Nadine joint author ZORA 700 1- Steffen Riccardo joint author ZORA 700 1- Schneider Hannah joint author ZORA 700 1- Luft Andreas R. joint author ZORA 700 1- Weller Michael joint author ZORA 700 1- Imthurn Bruno joint author ZORA 700 1- Merki-Feld Gabriele S. joint author ZORA 700 1- Wegener Susanne joint author ZORA 773 0- Cardiovascular Research 115(3):637-646 BK010053 XK010053 XK010000 ZORA ZORA ZORA Journal Article openAccess