| First Author | Barteczek P | Year | 2017 |
| Journal | J Cereb Blood Flow Metab | Volume | 37 |
| Issue | 1 | Pages | 291-306 |
| PubMed ID | 26746864 | Mgi Jnum | J:350586 |
| Mgi Id | MGI:6875208 | Doi | 10.1177/0271678X15624933 |
| Citation | Barteczek P, et al. (2017) Neuronal HIF-1alpha and HIF-2alpha deficiency improves neuronal survival and sensorimotor function in the early acute phase after ischemic stroke. J Cereb Blood Flow Metab 37(1):291-306 |
| abstractText | 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-alpha 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. |
