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Casas, A.I.* ; Kleikers, P.W.M.* ; Geuss, E.* ; Langhauser, F.* ; Adler, T. ; Busch, D.H.* ; Gailus-Durner, V. ; Hrabě de Angelis, M. ; Egea, J.* ; Lopez, M.G.* ; Kleinschnitz, C.* ; Schmidt, H.H.H.W.*

Calcium-dependent blood-brain barrier breakdown by NOX5 limits postreperfusion benefit in stroke.

J. Clin. Invest. 129, 1772-1778 (2019)
Verlagsversion Preprint Forschungsdaten DOI
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
lschemic stroke is a predominant cause of disability worldwide, with thrombolytic or mechanical removal of the occlusion being the only therapeutic option. Reperfusion bears the risk of an acute deleterious calcium-dependent breakdown of the blood-brain barrier. Its mechanism, however, is unknown. Here, we identified type 5 NADPH oxidase (NOX5), a calciumactivated, ROS-forming enzyme, as the missing link. Using a humanized knockin (KI) mouse model and in vitro organotypic cultures, we found that reoxygenation or calcium overload increased brain ROS levels in a NOX5-dependent manner. In vivo, postischemic ROS formation, infarct volume, and functional outcomes were worsened in NOXS-KI mice. Of clinical and therapeutic relevance, in a human blood-barrier model, pharmacological NOX inhibition also prevented acute reoxygenationinduced leakage. Our data support further evaluation of poststroke recanalization in the presence of NOX inhibition for limiting stroke-induced damage.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Calcium ; Hypoxia ; Neuroscience ; Pharmacology ; Therapeutics; Nadph Oxidase; Independent Predictor; Therapeutic Targets; Neuroprotection; Angiogenesis; Injury; Count
ISSN (print) / ISBN 0021-9738
e-ISSN 1558-8238
Quellenangaben Band: 129, Heft: 4, Seiten: 1772-1778 Artikelnummer: , Supplement: ,
Verlag American Society of Clinical Investigation
Verlagsort 2015 Manchester Rd, Ann Arbor, Mi 48104 Usa
Begutachtungsstatus Peer reviewed