Temperature-regulated model of focal ischemia in the mouse: a study with histopathological and behavioral outcomes.
Barber PA., Hoyte L., Colbourne F., Buchan AM.
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 degrees 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 degrees C+/-0.8 degrees C) was significantly different than the self-regulating (MCAO-45, mean 33.1 degrees C+/-2.3 degrees 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.