Protective effect of vitamin E against focal brain ischemia and neuronal death through induction of target genes of hypoxia-inducible factor-1

B. Zhang, J. Tanaka, L. Yang, L. Yang, M. Sakanaka, R. Hata, N. Maeda, N. Mitsuda

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Vitamin E has been shown to have protective effects against cerebral ischemia, possibly due to its anti-oxidant effects. However, its non-anti-oxidant, intracellular molecular mechanism remains elusive. For in vivo experiments in rats, orally administered vitamin E significantly reduced not only the brain infarct volume but also space navigation disability after permanent middle cerebral artery (MCA) occlusion. The level of anti-oxidant after MCA occlusion was significantly increased specifically in the ipsilateral brain tissues of vitamin E-treated rats. For in vitro experiments, posttreatment with vitamin E protected primary cultured neurons from nitric oxide-induced insult. Vitamin E induced the expression of the α subunit of hypoxia-inducible factor-1 (HIF-1) and its target genes, including vascular endothelial growth factor (VEGF) and heme oxygenase-1. The hypoxia response element on the VEGF promoter was responsible for this vitamin E-induced transcriptional activation of VEGF gene. Taken together, these results suggest that cerebral infarction increased the permeability of vitamin E across the blood-brain barrier, and this increased vitamin E in brain tissue elicited neuroprotective effects not only through scavenging oxidants, as are previously well reported, but also by transactivating HIF-1-dependent genes, which results in protection of brains from ischemic insults.

Original languageEnglish
Pages (from-to)433-440
Number of pages8
Issue number2
Publication statusPublished - 28-06-2004


All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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