Role of hypoxia-inducible factor-1 in hypoxia-induced ischemic tolerance in neonatal rat brain

Marcelle Bergeron, Jeffrey M. Gidday, Y. Yu Aimee, Gregg L. Semenza, Donna M. Ferriero, Frank R Sharp

Research output: Contribution to journalArticle

367 Scopus citations

Abstract

Hypoxia-inducible factor-1 (HIF-1) is a heterodimer composed of HIF-1α and HIF-1β protein subunits. This transcription factor is essential for the activation of hypoxia-inducible genes like erythropoietin, some glucose transporters, the glycolytic enzymes, and vascular endothelial growth factor. Because HIF-1 activation may promote cell survival in hypoxic tissues, we studied the effect of hypoxic preconditioning on HIF-1 expression in neonatal rat brain. Hypoxic preconditioning (8% O2 for 3 hours), a treatment known to protect the newborn rat brain against hypoxic-ischemic injury, markedly increased HIF-1α and HIF-1β expression. To support the role of HIF-1 in protective preconditioning, we also studied the effect of two other known HIF-1 inducers, cobalt chloride (CoCl2) and desferrioxamine (DFX), on HIF-1 expression and neuroprotection in newborn brain. HIF-1α and HIF-1β protein levels were markedly increased after intraperitoneal injection of CoCl2 (60 mg/kg) and moderately increased after intraperitoneal injection of DFX (200 mg/kg) 1 to 3 hours after the injections. Preconditioning with CoCl2 or DFX 24 hours before hypoxia-ischemia afforded 75 and 56% brain protection, respectively, compared with that in vehicle-injected littermate controls. Thus, HIF-1 activation could contribute to protective brain preconditioning, which could be used in high-risk deliveries and other clinical situations.

Original languageEnglish (US)
Pages (from-to)285-296
Number of pages12
JournalAnnals of Neurology
Volume48
Issue number3
DOIs
StatePublished - 2000

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Role of hypoxia-inducible factor-1 in hypoxia-induced ischemic tolerance in neonatal rat brain'. Together they form a unique fingerprint.

  • Cite this