Induction of cerebral ischemic tolerance by erythromycin preconditioning reprograms the transcriptional response to ischemia and suppresses inflammation

Ines Koerner, Matthias Gatting, Ruediger Noppens, Oliver Kempski, Ansgar Brambrink

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

BACKGROUND: A single dose of the macrolide antibiotic erythromycin can induce tolerance against cerebral ischemia in vivo (pharmacologic preconditioning). This study identified potential mechanisms of tolerance induction by assessing effects of erythromycin preconditioning on the cerebral transcriptional response to transient global cerebral ischemia. METHODS: Preconditioned and nonpreconditioned rats were exposed to 15 min of global cerebral ischemia, and changes in cerebral gene expression were identified by complementary DNA expression array and quantified by real-time reverse-transcription polymerase chain reaction. RESULTS: Ischemia caused a widespread up-regulation of transcription in nonpreconditioned brains in this model. Tolerance induction by erythromycin preconditioning reversed this pattern and caused a net down-regulation of a majority of genes, effectively reprogramming the brain's response pattern to ischemia. The most striking change in transcriptional response found in preconditioned animals was an almost complete suppression of the otherwise profound induction of proinflammatory genes by global ischemia. In contrast, the same treatment had little effect on the expression of apoptosis-inducing genes after ischemia. CONCLUSIONS: These findings present a new molecular correlate for the induction of ischemic tolerance achieved by erythromycin preconditioning and will further the understanding of this clinically important new regimen of preemptive neuroprotection.

Original languageEnglish (US)
Pages (from-to)538-547
Number of pages10
JournalAnesthesiology
Volume106
Issue number3
DOIs
StatePublished - Mar 2007

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Erythromycin
Ischemia
Inflammation
Brain Ischemia
Genes
Transient Ischemic Attack
Macrolides
Brain
Oligonucleotide Array Sequence Analysis
Reverse Transcription
Up-Regulation
Down-Regulation
Complementary DNA
Apoptosis
Anti-Bacterial Agents
Gene Expression
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Induction of cerebral ischemic tolerance by erythromycin preconditioning reprograms the transcriptional response to ischemia and suppresses inflammation. / Koerner, Ines; Gatting, Matthias; Noppens, Ruediger; Kempski, Oliver; Brambrink, Ansgar.

In: Anesthesiology, Vol. 106, No. 3, 03.2007, p. 538-547.

Research output: Contribution to journalArticle

Koerner, Ines ; Gatting, Matthias ; Noppens, Ruediger ; Kempski, Oliver ; Brambrink, Ansgar. / Induction of cerebral ischemic tolerance by erythromycin preconditioning reprograms the transcriptional response to ischemia and suppresses inflammation. In: Anesthesiology. 2007 ; Vol. 106, No. 3. pp. 538-547.
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