Alteration in HIF-1 DNA binding activity following cerebral ischemia and its therapeutic application

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Because iNOS is expressed in the ischemic brain, we tried to determine whether binding activity of hypoxia inducible factor (HIF) -1 to hypoxia-responsive enhancer (HRE) is increased in ischemic brain in the rat employing the electrophoretic mobility shift assay (EMSA) technique.One hour after 2-hour transient occlusion of the middle cerebral artery, hypoxia inducible factor (HIF) -1 binding activity was increased in the ischemic core and its surrounding area (penumbra). Six hours after ischemia, it was detected even in the contralateral hemisphere. In the penumbra, the activity was remained until 24 hours later, while it disappeared in the core. iNOS was induced during 12-48 hours after ischemia in the vessel walls and polymorphonuclear leukocytes within the ischemic territory.Energy failure in the ischemic core and involvement of the other transcription factors such as IRF-1 and NFκB might explain the discrepancy between HIF-1 binding activity and iNOS induction after cerebral ischemia.