Penmnent occlusion of bilateral internal carotid arteries after intemittent occlusion of bilateral carotid arteries： a new rat model for vascular dementia

Abstract

Objective To modify a classic two-vessel occlusion （2VO） modeling method in order to decrease the systematic errors in the behavioral experiments such as Morris water maze： Methods Thirty-two adult male Wistar rats were randomly allocated into classic 2VO model, modified model, sham operation and sham ligation groups （n =8 in each group）. Only the bilateral common carotid arteries were ligated in the classic 2VO model group; the common carotid arteries were clipped intermittently, and the origins of pterygopalatine arteries of the internal carotid arteries were high selectively ligated in the modified model group; the common carotid arteries were only ligated intermittently in the sham ligation group; and only the common carotid arteries and the upper segrnent of pterygopalatine artery branches were separated in the sham operation group. The rat behavior was evaluated using the pupillary light reflex, Morris water maze and eight-arm radial maze. HE staining was used to observe the histological changes. Results The Morris water maze escape latency （F = 72. 169 - 163. 102, all P 〈 0. 001） and the number of reference memory errors of eight-arm radial maze （F =33. 515 -74. 726, all P〈0. 001） in the modified model and the classic 2VO model groups were longer and higher than those in the sham operation group. The pupillary light reflex of the rats was lost in the classic 2VO model group and the pupillary light reflex of the rats was normal in other groups. The reaching platform time in the classic 2VO model group was significantly longer than that in the modified model and sham operation groups （P 〈0. 001 ）. The percentage of target quadrant dwell time was also decreased significantly （at day 7 after procedure： F = 13. 770, P 〈0. 001; at day 90 after procedure： F = 14. 780, P 〈0. 001）. HE staining showed pathological changes such as the cells decrease in hippocampal CA1 region and leukoaraiosis in the modified model and the classic 2VO model groups. In addition, there were more vacuole-like changes in the rat optic nerve region in the classic 2VO model group, while there were no such changes in the modified model group.Conclusions Estab- fishing vascular dementia model with permanent occlusion of bilateral internal carotid arteries after intermittent occlusion of bilateral carotid arteries could avoid severe visual impairment in rats. In the Morris water maze and eight-arm maze test, the modified model rats showed significant decrease in learning and memory abilities and had hippocampal damage. Key words: Dementia, Vascular; Disease Models, Animal; Rats