Laser-Doppler scanning of local cerebral blood flow and reserve capacity and testing of motor and memory functions in a chronic 2-vessel occlusion model in rats

Abstract

Background and Purpose - An animal model of incomplete forebrain ischemia resembling human hemodynamic insufficiency was established. The model allows examination of acute and chronic changes of local cerebral blood flow (ICBF) and reserve capacity in correlation with behavioral parameters. Methods - Anesthetized male Wistar-Kyoto rats underwent bilateral carotid occlusion (BCO). Laser-Doppler scanning of ICBF at baseline conditions and after acetazolamide was done 30 minutes after BCO, motor and memory function tests were administered after 1 and 2 days, and both investigations were repeated after 1, 2, 4, and 6 weeks. A sham-operated and a control group without any vessel manipulation served as controls. Results - ICBF dropped within 60 minutes after surgery by 62% (P<0.001) in 10 animals surviving BCO (BCO(survival)) and by 69% in 5 rats that died within 9 days (BCO(lethal)). Acetazolamide increased ICBF to 142.33% in controls, to 136.66% in sham- operated rats (both significant), and to 104.80% in BCO(survival) (not significant), and it decreased flow by 23.1% in BCO(lethal) rats (P<0.001). Baseline ICBF normalized within 4 weeks. Total motor function scores were significantly reduced from 9 points preoperatively to 5.80±0.65 in BCO(lethal) and 6.68±0.54 points in BCO(survival) rats 1 day after occlusion. Memory retention function remained impaired after BCO, as did the acetazolamide response, which correlated with motor score and was inversely related to maze exploration time. Conclusions - This model allows long-term follow-up of cerebral function, ICBF, and reserve capacity in a pathophysiological setting similar to hemodynamic insufficiency in humans.