Neuronal HIF-1α and HIF-2α deficiency improves neuronal survival and sensorimotor function in the early acute phase after ischemic stroke

• Verfasst von: Barteczek, Philipp [VerfasserIn]
• Verfasst von: Li, Lexiao [VerfasserIn]
• Verfasst von: Ernst, Anne-Sophie [VerfasserIn]
• Verfasst von: Böhler, Laura-Inés [VerfasserIn]
• Verfasst von: Marti, Hugo [VerfasserIn]
• Verfasst von: Kunze, Reiner [VerfasserIn]
• 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
• DOI: doi:10.1177/0271678X15624933
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1581440197

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.