Progressive cognitive impairment following chronic cerebral hypoperfusion induced by permanent occlusion of bilateral carotid arteries in rats.

The effects of chronic cerebral hypoperfusion induced by permanent occlusion of bilateral common carotid arteries (2VO) on learning and memory performance were examined in rats using an eight-arm radial maze task. The learning of the task was severely impaired in the permanent 2VO rats that had not been pretrained, while the retention was slightly impaired and soon recovered in the permanent 2VO rats that had been fully pretrained when tested within 1 month after the 2VO operation. The performance, however, was impaired in the pretrained rats when a 3-min delay was interposed between the fourth and fifth choices. Moreover, when retrained in the radial maze 4 months after the permanent 2VO, these same rats showed a performance impairment. Some loss of the hippocampal pyramidal neurons was observed 1 month after the permanent 2VO, although the decrease was not significant. However, significant loss of the cells was observed in the hippocampus CA1 subfield 4 months after the operation. We concluded that: (1) In the early stage (1 month after permanent 2VO), a learning deficit was observed in the non-pretrained rats. In the pretrained rats, working memory was not impaired, whereas longer term memory was compromised; (2) in the late stage (4 months after permanent 2VO), working memory may have also been impaired in the pretrained rats; and (3) this progressive cognitive deficit seemed to parallel the progress of neuronal damage.