Neuron-Specific Inactivation of the Hypoxia Inducible Factor 1 Increases Brain Injury in a Mouse Model of Transient Focal Cerebral Ischemia
Open Access
- 6 June 2007
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 27 (23), 6320-6332
- https://doi.org/10.1523/jneurosci.0449-07.2007
Abstract
In the present study, we show a biphasic activation of hypoxia inducible factor 1α (HIF-1) after stroke that lasts for up to 10 d, suggesting the involvement of the HIF pathway in several aspects of the pathophysiology of cerebral ischemia. We provide evidence that HIF-1-mediated responses have an overall beneficial role in the ischemic brain as indicated by increased tissue damage and reduced survival rate of mice with neuron-specific knockdown of HIF-1α that were subjected to transient focal cerebral ischemia. In addition, we demonstrated that drugs known to activate HIF-1 in cultured cells as well as in vivo had neuroprotective properties in this model of cerebral ischemia. This protective effect was significantly attenuated but not completely abolished in neuron-specific HIF-1α-deficient mice, suggesting that alternative mechanisms of neuroprotection are also implicated. Last, our study showed that hypoxia-induced tolerance to ischemia was preserved in neuron-specific HIF-1α-deficient mice, indicating that the neuroprotective effects of hypoxic preconditioning do not depend on neuronal HIF-1 activation.Keywords
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