RT Journal Article
SR Electronic
T1 Neuron-Specific Inactivation of the Hypoxia Inducible Factor 1α Increases Brain Injury in a Mouse Model of Transient Focal Cerebral Ischemia
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 6320
OP 6332
DO 10.1523/JNEUROSCI.0449-07.2007
VO 27
IS 23
A1 Oxana Baranova
A1 Luis F. Miranda
A1 Paola Pichiule
A1 Ioannis Dragatsis
A1 Randall S. Johnson
A1 Juan C. Chavez
YR 2007
UL http://www.jneurosci.org/content/27/23/6320.abstract
AB 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.