Maria Shvedova1, Mohammad Rashedul Islam2, Antonis A Armoundas2, Nina D Anfinogenova3, Christiane D Wrann4, Dmitriy N Atochin5. 1. Massachusetts General Hospital, Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Harvard Medical School, Charlestown, MA, USA; Massachusetts General Hospital, Endocrine Unit, Harvard Medical School, Boston, MA, United States(1). 2. Massachusetts General Hospital, Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Harvard Medical School, Charlestown, MA, USA. 3. Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia. 4. Massachusetts General Hospital, Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Harvard Medical School, Charlestown, MA, USA; McCance Center for Brain Health, Massachusetts General Hospital, Boston, MA, USA. 5. Massachusetts General Hospital, Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Harvard Medical School, Charlestown, MA, USA. Electronic address: atochin@cvrc.mgh.harvard.edu.
Abstract
BACKGROUND: Middle cerebral artery occlusion (MCAO) with 1 -h ischemia followed by reperfusion is a widely used stroke model in rodents that has significant limitations such as high mortality and severe neurological deficit hampering comprehensive neurobehavioral evaluation. The goal of this study was to establish a mouse model of 30-minute MCAO followed by 48 h of reperfusion and compare it with 1 -h MCAO followed by 24 h of reperfusion. NEW METHOD: Here we propose a modified MCAO model that is favorable for both neurobehavioral and infarct volume evaluation. The model includes shorter ischemic time (30 min) of MCAO followed by 48 h of reperfusion and use of standardized intraoperative partial and total reperfusion, which allows for the detailed evaluation of initial and total reperfusion by means of the monitoring of CBF by LDF. RESULTS AND COMPARISON WITH EXISTING METHOD: Intraoperative CBF parameters and infarct volume (1-h MCAO at 24 h: 69 ± 9; 30-minute MCAO at 48 h: 65 ± 14 mm3) did not significantly differ between groups. Neurological deficit was less severe in 30-minute MCAO group where mice also had significantly longer ambulatory distance and time, lower resting time, and higher vertical count on the OPF. The latency to fall in the rotarod test was significantly higher in 30-minute MCAO group. The mortality was higher after 1 -h MCAO. CONCLUSIONS: 30-minute MCAO followed by 48 h of reperfusion causes intraoperative ischemia, reperfusion and infarct volume comparable with 1 -h MCAO followed by 24 h of reperfusion but results in lower mortality with milder neurological deficit allowing for more extensive neurobehavioral evaluation.
BACKGROUND: Middle cerebral artery occlusion (MCAO) with 1 -h ischemia followed by reperfusion is a widely used stroke model in rodents that has significant limitations such as high mortality and severe neurological deficit hampering comprehensive neurobehavioral evaluation. The goal of this study was to establish a mouse model of 30-minute MCAO followed by 48 h of reperfusion and compare it with 1 -h MCAO followed by 24 h of reperfusion. NEW METHOD: Here we propose a modified MCAO model that is favorable for both neurobehavioral and infarct volume evaluation. The model includes shorter ischemic time (30 min) of MCAO followed by 48 h of reperfusion and use of standardized intraoperative partial and total reperfusion, which allows for the detailed evaluation of initial and total reperfusion by means of the monitoring of CBF by LDF. RESULTS AND COMPARISON WITH EXISTING METHOD: Intraoperative CBF parameters and infarct volume (1-h MCAO at 24 h: 69 ± 9; 30-minute MCAO at 48 h: 65 ± 14 mm3) did not significantly differ between groups. Neurological deficit was less severe in 30-minute MCAO group where mice also had significantly longer ambulatory distance and time, lower resting time, and higher vertical count on the OPF. The latency to fall in the rotarod test was significantly higher in 30-minute MCAO group. The mortality was higher after 1 -h MCAO. CONCLUSIONS: 30-minute MCAO followed by 48 h of reperfusion causes intraoperative ischemia, reperfusion and infarct volume comparable with 1 -h MCAO followed by 24 h of reperfusion but results in lower mortality with milder neurological deficit allowing for more extensive neurobehavioral evaluation.
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