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Verfasst von:Barteczek, Philipp [VerfasserIn]   i
 Li, Lexiao [VerfasserIn]   i
 Ernst, Anne-Sophie [VerfasserIn]   i
 Böhler, Laura-Inés [VerfasserIn]   i
 Marti, Hugo [VerfasserIn]   i
 Kunze, Reiner [VerfasserIn]   i
Titel:Neuronal HIF-1α and HIF-2α deficiency improves neuronal survival and sensorimotor function in the early acute phase after ischemic stroke
Verf.angabe:Philipp Barteczek, Lexiao Li, Anne-Sophie Ernst, Laura-Inés Böhler, Hugo H Marti and Reiner Kunze
Jahr:2017
Jahr des Originals:2016
Umfang:16 S.
Fussnoten:Received: July 21, 2015; Revisions received: October 30, 2015; Accepted: December 07, 2015; First Published January 8, 2016 ; Gesehen am 01.10.2018
Titel Quelle:Enthalten in: Journal of critical care
Ort Quelle:Philadelphia, Pa. : Saunders, 1986
Jahr Quelle:2017
Band/Heft Quelle:37(2017), 1, Seite 291-306
ISSN Quelle:1557-8615
Abstract:Hypoxia-inducible factors mediate adaptive responses to ischemia, among others, by induction of anti- and pro-survival genes. Thus, the impact of HIF on neuronal survival upon stroke is controversial. Therefore, neuron-specific knockout mice deficient for Hif1a and Hif2a were exposed to inspiratory hypoxia or ischemia-reperfusion injury. Both Hif1a- and Hif2a-deficient mice showed no altered infarct and edema size, suggesting that both HIF-α subunits might compensate for each other. Accordingly, hypoxic HIF-target gene regulation was marginally affected with exception of anti-survival Bnip3 and pro-survival erythropoietin. In the early acute stage upon stroke, Hif1a/Hif2a double knockout mice exhibited significantly reduced expression of the anti-survival Bnip3, Bnip3L, and Pmaip1. Accordingly, global cell death and edema were significantly reduced upon 24 h but not 72 h reperfusion. Behavioral assessment indicated that Hif1a/Hif2a-deficient mice initially performed better, but became significantly more impaired after 72 h accompanied by increased apoptosis and reduced angiogenesis. Our findings suggest that in neurons HIF-1 and HIF-2 have redundant functions for cellular survival under ischemic conditions. By contrast, lack of anti-survival factors in Hif1a/Hif2a-deficient mice might protect from early acute neuronal cell death and neurological impairment, indicating a benefit of HIF-pathway inhibition in neurons in the very acute phase after ischemic stroke.
DOI:doi:10.1177/0271678X15624933
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext ; Verlag: http://dx.doi.org/10.1177/0271678X15624933
 Volltext: https://doi.org/10.1177/0271678X15624933
 DOI: https://doi.org/10.1177/0271678X15624933
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1581440197
Verknüpfungen:→ Zeitschrift

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