Neuron-specific inactivation of the hypoxia inducible factor 1α increases brain injury in a mouse model of transient focal cerebral ischemia

Oxana Baranova, Luis F. Miranda, Paola Pichiule, Ioannis Dragatsis, Randall S. Johnson, Juan C. Chavez

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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.

Original languageEnglish (US)
Pages (from-to)6320-6332
Number of pages13
JournalJournal of Neuroscience
Volume27
Issue number23
DOIs
StatePublished - Jun 6 2007

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Hypoxia-Inducible Factor 1
Transient Ischemic Attack
Brain Injuries
Neurons
Brain Ischemia
Neuroprotective Agents
Cultured Cells
Ischemia
Stroke
Brain
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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Neuron-specific inactivation of the hypoxia inducible factor 1α increases brain injury in a mouse model of transient focal cerebral ischemia. / Baranova, Oxana; Miranda, Luis F.; Pichiule, Paola; Dragatsis, Ioannis; Johnson, Randall S.; Chavez, Juan C.

In: Journal of Neuroscience, Vol. 27, No. 23, 06.06.2007, p. 6320-6332.

Research output: Contribution to journalArticle

Baranova, Oxana ; Miranda, Luis F. ; Pichiule, Paola ; Dragatsis, Ioannis ; Johnson, Randall S. ; Chavez, Juan C. / Neuron-specific inactivation of the hypoxia inducible factor 1α increases brain injury in a mouse model of transient focal cerebral ischemia. In: Journal of Neuroscience. 2007 ; Vol. 27, No. 23. pp. 6320-6332.
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