Selective inhibition of early-but not late-expressed HIF-1α is neuroprotective in rats after focal ischemic brain damage

Shiu Hwa Yeh, Li Chin Ou, Po Wu Gean, Jan Jong Hung, Wen Chang Chang

Research output: Contribution to journalArticle

59 Citations (Scopus)


The expression of hypoxia-inducible factor-1-alpha (HIF-1α) is upregulated in ischemic stroke, but its function is still unclear. In the present study, biphasic expression of HIF-1α was observed during 1-12 h and after 48 h in neurons exposed to ischemic stress in vitro and in vivo. Treating neurons with 2-methoxyestradiol (2ME2) 0.5 h after ischemic stress or pre-silencing HIF-1α with small interfering RNA (siRNA) decreased brain injury, brain edema and number of apoptotic cell, and downregulates Nip-like protein X (Nix) expression. Conversely, applying 2ME2 to neurons 8 h after ischemic stress or silencing the HIF-1α with siRNA 12 h after oxygen-glucose deprivation (OGD) increased neuron damage and decreased vascular endothelial growth factor (VEGF) expression. Taken together, these results demonstrate that HIF-1α induced by ischemia in early and late times leads cellular apoptosis and survival, respectively, and provides a new insight into the divergent roles of HIF-1α expression in neurons after ischemic stroke.

Original languageEnglish
Pages (from-to)249-262
Number of pages14
JournalBrain Pathology
Issue number3
Publication statusPublished - May 2011
Externally publishedYes



  • 2ME2
  • cultured cortical neurons
  • HIF-1
  • MCAO
  • OGD
  • VEGF

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pathology and Forensic Medicine
  • Clinical Neurology

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