Drug-Induced Hypothermia as Beneficial Treatment before and after Cerebral Ischemia

TY - JOUR

T1 - Drug-Induced Hypothermia as Beneficial Treatment before and after Cerebral Ischemia

AU - Johansen, Flemming F

AU - Hasseldam, Henrik

AU - Rasmussen, Rune Skovgaard

AU - Bisgård, Anne Sofie

AU - Bonfils, Peter Kramshøj

AU - Poulsen, Steen Seier

AU - Hansen-Schwartz, Jacob

N1 - Copyright © 2013 S. Karger AG, Basel.

PY - 2013/10

Y1 - 2013/10

N2 - Objectives: Hypothermia is still unproven as beneficial treatment in human stroke, although in animal models, conditioning the brain with hypothermia has induced tolerance to insults. Here, we delineate the feasibility of drug-induced mild hypothermia in reducing ischemic brain damage when conditioning before (preconditioning) and after (postconditioning) experimental stroke. Methods: Hypothermia was induced in rats with a bolus of 6 mg/kg talipexole followed by 20 h continuous talipexole infusion of 6 mg/kg in total. Controls received similar treatment with saline. The core body temperature was continuously monitored. In preconditioning, hypothermia was terminated before either reversible occlusion of the middle cerebral artery (MCAO) for 60 min or global ischemia for 10 min with 2-vessel occlusion and hypotension. In postconditioning, rats experienced 60 min of MCAO before hypothermia was induced either immediately or with 3 h delay. Rats survived ischemia for 2, 7 or 90 days. Infarct volumes were quantified by stereology. Additional experiments of methodological relevance were included in the study. Results: Talipexole induced mild hypothermia (35.1 ± 1.1 to 36.0 ± 0.5°C) for

AB - Objectives: Hypothermia is still unproven as beneficial treatment in human stroke, although in animal models, conditioning the brain with hypothermia has induced tolerance to insults. Here, we delineate the feasibility of drug-induced mild hypothermia in reducing ischemic brain damage when conditioning before (preconditioning) and after (postconditioning) experimental stroke. Methods: Hypothermia was induced in rats with a bolus of 6 mg/kg talipexole followed by 20 h continuous talipexole infusion of 6 mg/kg in total. Controls received similar treatment with saline. The core body temperature was continuously monitored. In preconditioning, hypothermia was terminated before either reversible occlusion of the middle cerebral artery (MCAO) for 60 min or global ischemia for 10 min with 2-vessel occlusion and hypotension. In postconditioning, rats experienced 60 min of MCAO before hypothermia was induced either immediately or with 3 h delay. Rats survived ischemia for 2, 7 or 90 days. Infarct volumes were quantified by stereology. Additional experiments of methodological relevance were included in the study. Results: Talipexole induced mild hypothermia (35.1 ± 1.1 to 36.0 ± 0.5°C) for

U2 - 10.1159/000352026

DO - 10.1159/000352026

M3 - Journal article

C2 - 23989388

SN - 1015-2008

VL - 81

SP - 42

EP - 52

JO - Pathobiology

JF - Pathobiology

IS - 1

ER -