title: Cerebral hypoperfusion yields capillary damage in the hippocampal CA1 area that correlates with spatial memory impairment.
abstract: The impact of chronic cerebral hypoperfusion on cognitive function and cerebral capillary morphology in the hippocampus was examined. Young adult Wistar rats were subjected to permanent ligation of both common carotid arteries (two-vessel occlusion). One month after vascular occlusion, a small but non-significant impairment in the acquisition of spatial information was registered 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 significant attenuation of the learning rate in the occluded rats group, whereas no significant differences in long-term retention were observed. Thus, chronic 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 examined using transmission electron microscopy. Typical age-related capillary abnormalities such as degenerative pericytes and thickened basement membranes (with or without fibrosis) were detected in the hippocampus of sham animals. In occluded rats, the occurrence of capillaries displaying such abnormalities almost doubled in the CA1 region, but was similar in the dentate gyrus, compared with sham controls. A highly significant correlation was found between the last Morris maze performance and the percentage of capillaries with deposits in the basement membrane in the hippocampal CA1 area of occluded rats, which was not present in the sham animals. We conclude that a long-term hypoperfusion accelerated the development of age-related ultrastructural aberrations of capillaries in the hippocampal CA1 area, but not in the dentate gyrus. Thus, not only neurons, but also capillaries in the hippocampal CA1 area are sensitive to an impaired microcirculation. 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 function in conditions that compromise cerebral microcirculation.
authors.affiliation: Department of Animal Physiology, Graduate School for Behavioral and Cognitive Neuroscience, University of Groningen, The Netherlands.
authors.forename: G I
authors.initials: GI
authors.lastname: De Jong
authors.forename: E
authors.initials: E
authors.lastname: Farkas
authors.forename: C M
authors.initials: CM
authors.lastname: Stienstra
authors.forename: J R
authors.initials: JR
authors.lastname: Plass
authors.forename: J N
authors.initials: JN
authors.lastname: Keijser
authors.forename: J C
authors.initials: JC
authors.lastname: de la Torre
authors.forename: P G
authors.initials: PG
authors.lastname: Luiten
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000473:pathology* / Q000523:psychology*; D002196:Capillaries / Q000473:pathology / Q000648:ultrastructure; D002560:Cerebrovascular Circulation / Q000502:physiology; D006624:Hippocampus / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000473:pathology* / Q000523:psychology*; D008854:Microscopy, Electron; D051381:Rats; D017208:Rats, Wistar; D013028:Space Perception / Q000502:physiology*