CHRONIC REDUCTION OF CEREBRAL BLOOD-FLOW IN THE ADULT-RAT - LATE-EMERGING CA1 CELL LOSS AND MEMORY DYSFUNCTION

Ten-month-old rats were subjected to permanent bilateral occlusion of both common carotid arteries (2-VO) to chronically but moderately redu ce brain blood flow. 2-VO impaired Morris water maze acquisition as so on as 7 days post-surgery. 2-VO also caused a later-appearing impairme nt on the radial arm maze which did not reach significance until 63 da ys post-surgery. At 14 dats post-surgery there were no effects of 2-VO on hippocampal CA1 pyramidal cell number or density of glial fibrilla ry acidic protein (GFAP). Hippocampal choline acetyltransferase activi ty at 70 days was also unaffected by 2-VO. At 190 days post-surgery, h owever, the 2-VO rats showed loss of cells and increased GFAP density in CA1. The increased density of hippocampal GFAP correlated with radi al arm maze but not Morris water maze impairment. It is suggested that 2-VO causes neuronal dysfunction which can be exacerbated by stress a nd thereby manifested on aversively motivated tasks such as the water maze. As well, CA1 neurons begin to degenerate after several weeks of the reduced energy availability caused by 2-VO and this impairs memory . Since reduced neuronal energy metabolism is associated with the prog ressive neurodegeneration that underlies disorders such as Alzheimer's , research should further explore the possibility that the effects of 2-VO may model age-related dementia.