A rat model of vascular dementia for evaluating Chinese medicine prescriptions

Objective To develop a new model of vascular dementia for evaluating Chinese medicine prescriptions. Methods Eighty-eight male Wistar rats were randomly divided into 4 groups. At d 00 , d 42 , d 70 , d 98 (n i =20, 20, 24, 24) during fatty-feeding, rats in each group were further divided into 10 or 12 subgroups (n i =2), respectively. Lacunar stroke were replicated with the injection of thrombi which coagulated artificially from itself blood. The median lethal doses (LD 50 ) were regressed from accumulative mortality in each geometric thrombus doses (k=0.75, 0.5, 0.85, 0.85), respectively. The degree of vascular dementia was evaluated as exploratory, learning and memorizing abilities. The median effective dose of thrombus for replicating rat model was regressed from dementia scores which were derived from the abilities. The linear correlation was regressed between the values of LD 50 or effective dose (ED 50 ) and the durations (days) of hypercholesterolemia. This model of vascular dementia was pathologically confirmed as the neural injuries from lacunar stroke in rats. Results The hypercholesterolemia was indicated as elevated total cholesterol, triglyeerides low-density lipoprotein cholesterol, and decreased high-density lipoprotein cholesterol. The values of LD5 0 with its 95% confidence intervals (CI) were 1525.0 (1361.0–1709.0), 584.3 (490.1–696.6), 168.7 (163.7–173.8), or 62.4 (59.5–65.4) mg/mL, at d 00 , d 42 , d 70 , and d 98 , respectively. There is a linear regression between the values of LD 50 and the durations of hypercholesterolemia (y=–15.33x+1390.0, r=0.963, P <0.05). The values of ED 50 with its 95% CI were 528.8 (340.5–821.4), 217.0 (20.84–2259.0), 96.3 (23.4–402.6), or 47.0 (43.7–50.6) mg/mL from dementia score, at d 00 , d 42 , d 70 , and d 98 , respectively. There is a linear regression between the values of ED 50 and the durations of hypercholesterolemia (y=–4.992x+484.2, r=0.965, P <0.05). The neural injuries were demonstrated as neural degeneration and necrosis. Conclusions For evaluating Chinese medicine, a model of vascular dementia in rats is set up with the lacunar stroke from self-thrombosis during hypercholesterolemia. This model from lacunar stroke is useful to investigate the pathogenesis and treatment of vascular dementia.