The antibiotic erythromycin induces tolerance against transient global cerebral ischemia in rats (pharmacologic preconditioning)

Ansgar Brambrink, Ines Koerner, Kathrin Diehl, Georg Strobel, Ruediger Noppens, Oliver Kempski

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

BACKGROUND: Cerebral ischemic tolerance can be induced by a variety of noxious stimuli, but no clinically applicable regimen for preconditioning has been described. Therefore, the authors tested the ability of a pharmacologic preconditioning strategy using the well-known macrolide antibiotic erythromycin to induce tolerance against transient global cerebral ischemia in vivo. They also investigated whether tolerance induction by erythromycin involves transcriptional and translational changes of cerebral B-cell leukemia/lymphoma-2 (bcl-2) expression. METHODS: Male Wistar rats were treated with erythromycin (25 mg/kg intramuscularly) or vehicle and subjected to 15 min of transient global cerebral ischemia 6, 12, or 24 h after pretreatment. Neurologic deficit was evaluated once daily, and neuronal cell survival was assessed after 7 days of reperfusion. Additional animals were similarly pretreated, and cerebral bcl-2 messenger RNA (mRNA) and protein expression was analyzed 6 and 24 h later. RESULTS: Erythromycin improved postischemic neuronal survival in hippocampal CA1 and CA3 sectors and reduced functional deficit, with 12 h being the most efficient pretreatment interval. Bcl-2 mRNA in hippocampus was transiently up-regulated 6 h after erythromycin, but neuronal Bcl-2 protein remained unchanged. CONCLUSIONS: Erythromycin can induce cerebral ischemic tolerance in vivo (pharmacologic preconditioning), suggesting a potential clinical strategy of preemptive neuroprotection. Changes in bcl-2 expression after erythromycin were small and transient. The induction of bcl-2-related pathways, although important for other preconditioning regimens, may therefore be less relevant for the neuroprotective effects of pharmacologic preconditioning using erythromycin.

Original languageEnglish (US)
Pages (from-to)1208-1215
Number of pages8
JournalAnesthesiology
Volume104
Issue number6
DOIs
StatePublished - Jun 2006

Fingerprint

Transient Ischemic Attack
Erythromycin
B-Cell Leukemia
Anti-Bacterial Agents
B-Cell Lymphoma
Hippocampal CA3 Region
Hippocampal CA1 Region
Messenger RNA
Macrolides
Neuroprotective Agents
Neurologic Manifestations
Reperfusion
Wistar Rats
Hippocampus
Cell Survival
Proteins

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

The antibiotic erythromycin induces tolerance against transient global cerebral ischemia in rats (pharmacologic preconditioning). / Brambrink, Ansgar; Koerner, Ines; Diehl, Kathrin; Strobel, Georg; Noppens, Ruediger; Kempski, Oliver.

In: Anesthesiology, Vol. 104, No. 6, 06.2006, p. 1208-1215.

Research output: Contribution to journalArticle

Brambrink, Ansgar ; Koerner, Ines ; Diehl, Kathrin ; Strobel, Georg ; Noppens, Ruediger ; Kempski, Oliver. / The antibiotic erythromycin induces tolerance against transient global cerebral ischemia in rats (pharmacologic preconditioning). In: Anesthesiology. 2006 ; Vol. 104, No. 6. pp. 1208-1215.
@article{3c132d771d4e4adc9231d40e3db2a39e,
title = "The antibiotic erythromycin induces tolerance against transient global cerebral ischemia in rats (pharmacologic preconditioning)",
abstract = "BACKGROUND: Cerebral ischemic tolerance can be induced by a variety of noxious stimuli, but no clinically applicable regimen for preconditioning has been described. Therefore, the authors tested the ability of a pharmacologic preconditioning strategy using the well-known macrolide antibiotic erythromycin to induce tolerance against transient global cerebral ischemia in vivo. They also investigated whether tolerance induction by erythromycin involves transcriptional and translational changes of cerebral B-cell leukemia/lymphoma-2 (bcl-2) expression. METHODS: Male Wistar rats were treated with erythromycin (25 mg/kg intramuscularly) or vehicle and subjected to 15 min of transient global cerebral ischemia 6, 12, or 24 h after pretreatment. Neurologic deficit was evaluated once daily, and neuronal cell survival was assessed after 7 days of reperfusion. Additional animals were similarly pretreated, and cerebral bcl-2 messenger RNA (mRNA) and protein expression was analyzed 6 and 24 h later. RESULTS: Erythromycin improved postischemic neuronal survival in hippocampal CA1 and CA3 sectors and reduced functional deficit, with 12 h being the most efficient pretreatment interval. Bcl-2 mRNA in hippocampus was transiently up-regulated 6 h after erythromycin, but neuronal Bcl-2 protein remained unchanged. CONCLUSIONS: Erythromycin can induce cerebral ischemic tolerance in vivo (pharmacologic preconditioning), suggesting a potential clinical strategy of preemptive neuroprotection. Changes in bcl-2 expression after erythromycin were small and transient. The induction of bcl-2-related pathways, although important for other preconditioning regimens, may therefore be less relevant for the neuroprotective effects of pharmacologic preconditioning using erythromycin.",
author = "Ansgar Brambrink and Ines Koerner and Kathrin Diehl and Georg Strobel and Ruediger Noppens and Oliver Kempski",
year = "2006",
month = "6",
doi = "10.1097/00000542-200606000-00016",
language = "English (US)",
volume = "104",
pages = "1208--1215",
journal = "Anesthesiology",
issn = "0003-3022",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - The antibiotic erythromycin induces tolerance against transient global cerebral ischemia in rats (pharmacologic preconditioning)

AU - Brambrink, Ansgar

AU - Koerner, Ines

AU - Diehl, Kathrin

AU - Strobel, Georg

AU - Noppens, Ruediger

AU - Kempski, Oliver

PY - 2006/6

Y1 - 2006/6

N2 - BACKGROUND: Cerebral ischemic tolerance can be induced by a variety of noxious stimuli, but no clinically applicable regimen for preconditioning has been described. Therefore, the authors tested the ability of a pharmacologic preconditioning strategy using the well-known macrolide antibiotic erythromycin to induce tolerance against transient global cerebral ischemia in vivo. They also investigated whether tolerance induction by erythromycin involves transcriptional and translational changes of cerebral B-cell leukemia/lymphoma-2 (bcl-2) expression. METHODS: Male Wistar rats were treated with erythromycin (25 mg/kg intramuscularly) or vehicle and subjected to 15 min of transient global cerebral ischemia 6, 12, or 24 h after pretreatment. Neurologic deficit was evaluated once daily, and neuronal cell survival was assessed after 7 days of reperfusion. Additional animals were similarly pretreated, and cerebral bcl-2 messenger RNA (mRNA) and protein expression was analyzed 6 and 24 h later. RESULTS: Erythromycin improved postischemic neuronal survival in hippocampal CA1 and CA3 sectors and reduced functional deficit, with 12 h being the most efficient pretreatment interval. Bcl-2 mRNA in hippocampus was transiently up-regulated 6 h after erythromycin, but neuronal Bcl-2 protein remained unchanged. CONCLUSIONS: Erythromycin can induce cerebral ischemic tolerance in vivo (pharmacologic preconditioning), suggesting a potential clinical strategy of preemptive neuroprotection. Changes in bcl-2 expression after erythromycin were small and transient. The induction of bcl-2-related pathways, although important for other preconditioning regimens, may therefore be less relevant for the neuroprotective effects of pharmacologic preconditioning using erythromycin.

AB - BACKGROUND: Cerebral ischemic tolerance can be induced by a variety of noxious stimuli, but no clinically applicable regimen for preconditioning has been described. Therefore, the authors tested the ability of a pharmacologic preconditioning strategy using the well-known macrolide antibiotic erythromycin to induce tolerance against transient global cerebral ischemia in vivo. They also investigated whether tolerance induction by erythromycin involves transcriptional and translational changes of cerebral B-cell leukemia/lymphoma-2 (bcl-2) expression. METHODS: Male Wistar rats were treated with erythromycin (25 mg/kg intramuscularly) or vehicle and subjected to 15 min of transient global cerebral ischemia 6, 12, or 24 h after pretreatment. Neurologic deficit was evaluated once daily, and neuronal cell survival was assessed after 7 days of reperfusion. Additional animals were similarly pretreated, and cerebral bcl-2 messenger RNA (mRNA) and protein expression was analyzed 6 and 24 h later. RESULTS: Erythromycin improved postischemic neuronal survival in hippocampal CA1 and CA3 sectors and reduced functional deficit, with 12 h being the most efficient pretreatment interval. Bcl-2 mRNA in hippocampus was transiently up-regulated 6 h after erythromycin, but neuronal Bcl-2 protein remained unchanged. CONCLUSIONS: Erythromycin can induce cerebral ischemic tolerance in vivo (pharmacologic preconditioning), suggesting a potential clinical strategy of preemptive neuroprotection. Changes in bcl-2 expression after erythromycin were small and transient. The induction of bcl-2-related pathways, although important for other preconditioning regimens, may therefore be less relevant for the neuroprotective effects of pharmacologic preconditioning using erythromycin.

UR - http://www.scopus.com/inward/record.url?scp=33744956901&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33744956901&partnerID=8YFLogxK

U2 - 10.1097/00000542-200606000-00016

DO - 10.1097/00000542-200606000-00016

M3 - Article

VL - 104

SP - 1208

EP - 1215

JO - Anesthesiology

JF - Anesthesiology

SN - 0003-3022

IS - 6

ER -