Cerebral hypoperfusion yields capillary damage in the hippocampal Ca1 areathat correlates with spatial memory impairment

The impact of chronic cerebral hypoperfusion on cognitive function and cere bral capillary morphology in the hippocampus was examined. Young adult Wist ar rats were subjected to permanent ligation of both common carotid arterie s (two-vessel occlusion). One month after vascular occlusion, a small but n on-significant impairment in the acquisition of spatial information was reg istered compared with sham-operated controls. Two months after surgery, the occluded animals displayed an impaired performance throughout the training period. One year after surgery, the acquisition curves demonstrated a sign ificant attenuation of the learning rate in the occluded rats group, wherea s no significant differences in long-term retention were observed. Thus, ch ronic hypoperfusion induced by two-vessel occlusion gave rise to impairment of spatial memory, Following behavioural testing, the rats were killed at the age of 17 months, and capillaries in the CA1 and dentate gyrus were exa mined using transmission electron microscopy. Typical age-related capillary abnormalities such as degenerative pericytes and thickened basement membra nes (with or without fibrosis) were detected in the hippocampus of sham ani mals. In occluded rats, the occurrence of capillaries displaying such abnor malities almost doubled in the CAI region, but was similar in the dentate g yrus, compared with sham controls. A highly significant correlation was fou nd between the last Morris maze performance and the percentage of capillari es with deposits in the basement membrane in the hippocampal CA1 area of oc cluded rats, which was not present in the sham animals. We conclude that a long-term hypoperfusion accelerated the development of a ge-related ultrastructural aberrations of capillaries in the hippocampal CA 1 area, but not in the dentate gyrus. Thus, not only neurons, but also capi llaries in the hippocampal CA1 area are sensitive to an impaired microcircu lation. Moreover, the cognitive performance of hypoperfused rats correlated closely with the condition of the capillaries in the CA1 area, suggesting that capillary integrity is one of the important determinants of brain func tion in conditions that compromise cerebral microcirculation. (C) 1999 IBRO . Published by Elsevier Science Ltd.