Published Online
on May 20, 2004

A more recent version of this article appeared on July 1, 2004

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Submitted on January 6, 2004
Revised on March 10, 2004
Accepted on March 30, 2004

Temperature-Regulated Model of Focal Ischemia in the Mouse: A Study With Histopathological and Behavioral Outcomes

Philip A. Barber MB ChB, MRCP(UK)^*; Lisa Hoyte BSc; Frederick Colbourne PhD; and Alastair M. Buchan BM FRCP

From the Department of Clinical Neurosciences (P.A.B., L.H., A.M.B.), University of Calgary, Calgary, Edmonton, Canada; and Department of Psychology and Centre for Neuroscience (F.C.), University of Alberta, Edmonton, Canada.

^* To whom correspondence should be addressed. E-mail: pabarber{at}ucalgary.ca.

Background and Purpose--The importance of mouse stroke models has increased with the development of genetically manipulated animals. We hypothesized that immediate postischemia hypothermia may attenuate ischemic brain injury in the mouse.

Methods--Intraabdominal radio frequency probes were implanted in animals and core temperature monitored. Groups included: MCAO-45-REG (45 minutes middle cerebral artery occlusion [MCAO]) temperature-controlled in the postischemic period >34°C for 24 hours; MCAO-45 (45 minutes MCAO) were allowed to self-regulate core temperature during recovery; MCAO-30-REG (30 minutes MCAO), with the same temperature protocol as MCAO-45-REG; MCAO-30 (30 minutes MCAO), with temperature protocol the same as MCAO-45. Behavior and histological score was assessed at 7 days. The qualitative histological score assessed for injury in 18 specified regions.

Results--MCAO-45-REG core temperature (mean 34.94°C±0.8°C) was significantly different than the self-regulating (MCAO-45, mean 33.1°C±2.3°C) for the first 4 hours after anesthesia (P<0.01). There was a trend toward similar differences in temperatures for MCAO-30-REG and MCAO-30 (P=0.08). At 7 days, a greater improvement in behavior score was observed for MCAO-45 and MCAO-30 compared with MCAO-45-REG and MCAO-30-REG (P<0.001). The histological score confirmed reduced injury in unregulated temperature groups (MCAO-45-REG mean 38±10 and MCAO-45 30±5.1, P<0.05; MCAO-30-REG 41±10 and MCAO-30 30±9, P<0.05).

Conclusions--Hypothermia is an important confounder of stroke injury in the intraluminal filament mouse model. Future mouse stroke studies must use strict temperature regulation.

Key words: ischemic attack, transient • hypothermia • behavior

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