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 (lCBF) and reserve capacity in correlation with behavioral parameters. Methods-Anesthetized male Wistar-Kyoto rats underwent bilateral carotid occlusion (BCO). Laser-Doppler scanning of lCBF 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-lCBF dropped within 60 minutes after surgery by 62% (PϽ0.001) in 10 animals surviving BCO (BCO survival ) and by 69% in 5 rats that died within 9 days (BCO lethal ). Acetazolamide increased lCBF 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 (PϽ0.001). Baseline lCBF normalized within 4 weeks. Total motor function scores were significantly reduced from 9 points preoperatively to 5.80Ϯ0.65 in BCO lethal and 6.68Ϯ0.54 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, lCBF, and reserve capacity in a pathophysiological setting similar to hemodynamic insufficiency in humans. (Stroke. 1998;29:2412-2420.)

Bilateral common carotid artery stenosis in normotensive rats impairs endothelium-dependent dilation of parenchymal arterioles

“…reserve capacity. Impaired response to acetazolamide has been observed immediately postocclusion in WKY rats with common carotid artery occlusion and this persisted for 4 wk (50).…”

The modified 2VO ischemia protocol causes cognitive impairment similar to that induced by the standard method, but with a better survival rate

“…Ischemia-induced neuronal degeneration is also observed in other structures, such as the striatum, cerebral cortex and thalamus (7)(8)(9). In this model, there is an abrupt reduction of whole brain blood flow, ranging from approximately 35-45% in the cortical area to 60% in the hippocampus compared to control levels (4,(10)(11)(12). This hypoperfusion is believed to sustain a chronic state of moderate hypoglycemia, a pathophysiological condition closely resembling that of reduced cerebral blood flow present in human aging and dementia (6).…”

A Mouse Model for Chronic Cerebral Hypoperfusion-induced Cognitive Dysfunction

“…Among the animal models of chronic cerebral hypoperfusion, permanent 2-VO has been widely used but has a high mortality rate and reduced blood flow to both cerebral hemispheres suddenly, which does not match the situations in patients (7)(8)(9). A study performed on adult C57BL/ 6J mice with permanent RCCAO showed that 1-VO induced non-spatial memory deficits detected by objective recognition test, but these mice did not have spatial memory deficits detected by T maze spontaneous alternation test.…”

“…The most widely used experimental model is permanent bilateral common carotid arteries occlusion (two-vessel occlusion, 2-VO) in rodents (7). Permanent 2-VO produces a sudden decrease of cerebral blood flow to both cerebral hemispheres by 30% to 40% of the control level (8), which does not simulate the gradual decline of the ce-…”