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PMID: 11973424 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism ·Vol. 22 ·No. 5 ·2002-05-00 ·Pages 520-5

Prass K, Ruscher K, Karsch M, Isaev N, Megow D, Priller J, Scharff A, Dirnagl U, Meisel A

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.

MeSH Terms

Animals Cell Survival/drug effects Cells, Cultured Cerebral Cortex/drug effects,metabolism Constriction Cycloheximide/pharmacology DNA-Binding Proteins/metabolism Deferoxamine/administration & dosage,therapeutic use Dose-Response Relationship, Drug Embryo, Mammalian Erythropoietin/genetics Gene Expression/drug effects Glucose/administration & dosage Hypoxia-Inducible Factor 1 Hypoxia-Inducible Factor 1, alpha Subunit Iron Chelating Agents/administration & dosage,therapeutic use Ischemic Attack, Transient/prevention & control Male Middle Cerebral Artery Neurons/drug effects,metabolism Nuclear Proteins/metabolism Oxygen/administration & dosage Protein Synthesis Inhibitors/pharmacology Rats Rats, Wistar Reperfusion Thiazoles/metabolism Thiazolidinediones Time Factors Transcription Factors

Chemicals

DNA-Binding Proteins Hif1a protein, rat Hypoxia-Inducible Factor 1 Hypoxia-Inducible Factor 1, alpha Subunit Iron Chelating Agents Nuclear Proteins Protein Synthesis Inhibitors Thiazoles Thiazolidinediones Transcription Factors Erythropoietin DN 108 Cycloheximide Glucose Deferoxamine Oxygen

Authors & Affiliations

9 authors, click to expand affiliations / ORCID

Prass Konstantin

Department of Neurology, Medical Faculty Charité, Humboldt-University, Berlin, Germany.

Ruscher Karsten

Karsch Maria

Isaev Nikolay

Megow Dirk

Priller Josef

Scharff Anna

Dirnagl Ulrich

Meisel Andreas

Article Info

Journal

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

Abbr.

J Cereb Blood Flow Metab

ISSN

0271-678X

DOI

10.1097/00004647-200205000-00003

Published

2002-05-00

Pages

520-5

Language

English

Region

United States

NLM ID

8112566

Subset

External Links

PubMed source DOI: 10.1097/00004647-200205000-00003 View journal details

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

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