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

doi:10.1097/00004647-200205000-00003

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 journal › Article › peer-review

Abstract

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 language	English
Pages (from-to)	520-5
Number of pages	6
Journal	Journal of Cerebral Blood Flow and Metabolism
Volume	22
Issue number	5
DOIs	https://doi.org/10.1097/00004647-200205000-00003
Publication status	Published - May 2002

Keywords

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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10.1097/00004647-200205000-00003

Cite this

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title = "Desferrioxamine induces delayed tolerance against cerebral ischemia in vivo and in vitro",

abstract = "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.",

keywords = "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",

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

year = "2002",

month = may,

doi = "10.1097/00004647-200205000-00003",

language = "English",

volume = "22",

pages = "520--5",

journal = "Journal of Cerebral Blood Flow and Metabolism",

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T1 - Desferrioxamine induces delayed tolerance against cerebral ischemia in vivo and in vitro

AU - Prass, Konstantin

AU - Ruscher, Karsten

AU - Karsch, Maria

AU - Isaev, Nikolay

AU - Megow, Dirk

AU - Priller, Josef

AU - Scharff, Anna

AU - Dirnagl, Ulrich

AU - Meisel, Andreas

PY - 2002/5

Y1 - 2002/5

N2 - 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.

AB - 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.

KW - Animals

KW - Cell Survival

KW - Cells, Cultured

KW - Cerebral Cortex

KW - Constriction

KW - Cycloheximide

KW - DNA-Binding Proteins

KW - Deferoxamine

KW - Dose-Response Relationship, Drug

KW - Embryo, Mammalian

KW - Erythropoietin

KW - Gene Expression

KW - Glucose

KW - Hypoxia-Inducible Factor 1

KW - Hypoxia-Inducible Factor 1, alpha Subunit

KW - Iron Chelating Agents

KW - Ischemic Attack, Transient

KW - Male

KW - Middle Cerebral Artery

KW - Neurons

KW - Nuclear Proteins

KW - Oxygen

KW - Protein Synthesis Inhibitors

KW - Rats

KW - Rats, Wistar

KW - Reperfusion

KW - Thiazoles

KW - Thiazolidinediones

KW - Time Factors

KW - Transcription Factors

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1097/00004647-200205000-00003

DO - 10.1097/00004647-200205000-00003

M3 - Article

C2 - 11973424

VL - 22

SP - 520

EP - 525

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 1559-7016

IS - 5

ER -

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

Abstract

Keywords

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