Desferrioxamine induces delayed tolerance against cerebral ischemia in vivo and in vitro

Konstantin Prass, Karsten Ruscher, Maria Karsch, Nikolay Isaev, Dirk Megow, Josef Priller, Anna Scharff, Ulrich Dirnagl, Andreas Meisel

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The widely prescribed drug desferrioxamine is a known activator of the hypoxia-inducible transcription factor 1 (HIF-1) and the subsequent transcription of erythropoietin. In the brain, HIF-1 is a master switch of the transcriptional response to hypoxia, whereas erythropoietin is a potent neuroprotectant. The authors show that desferrioxamine dose-dependently and time-dependently induces tolerance against focal cerebral ischemia in rats and mice, and against oxygen-glucose deprivation in purified cortical neurons. Desferrioxamine induced HIF-1 DNA binding and transcription of erythropoietin in vivo, the temporal kinetics of which were congruent with tolerance induction. Desferrioxamine is a promising drug for the induction of tolerance in humans when ischemia can be anticipated.

Original languageEnglish
Pages (from-to)520-5
Number of pages6
JournalJournal of Cerebral Blood Flow and Metabolism
Volume22
Issue number5
DOIs
Publication statusPublished - May 2002

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Cell Survival
  • Cells, Cultured
  • Cerebral Cortex
  • Constriction
  • Cycloheximide
  • DNA-Binding Proteins
  • Deferoxamine
  • Dose-Response Relationship, Drug
  • Embryo, Mammalian
  • Erythropoietin
  • Gene Expression
  • Glucose
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Iron Chelating Agents
  • Ischemic Attack, Transient
  • Male
  • Middle Cerebral Artery
  • Neurons
  • Nuclear Proteins
  • Oxygen
  • Protein Synthesis Inhibitors
  • Rats
  • Rats, Wistar
  • Reperfusion
  • Thiazoles
  • Thiazolidinediones
  • Time Factors
  • Transcription Factors
  • Journal Article
  • Research Support, Non-U.S. Gov't

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