Effects of aging and vincamine derivatives on pericapillary microenvironment: stereological characterization of the cerebral capillary network

Changes in the pericapillary microenvironment of adult (18-month-old) and senescent (27 1/2-month-old) Fischer-344 rats treated for 6 weeks with daily IP injections of brovincamine or apovincamine (0, 2.5, 5, 10 mg/kg) were correlated with spontaneous locomotor activity and [14C]-2-deoxyglucose uptake of the brain. The animals were tested for spontaneous locomotor activity in a tunnel maze. Twenty-four hr after behavioral testing and subsequently after a [14C]-2-deoxyglucose injection, brains were removed and capillaries stained with alkaline phosphatase reaction, being later measured with an optical-electronic image analysis technique. Results revealed an increase in intercapillary distance, as a sensitive parameter for capillary density, in the hippocampus (CA1) and in the parietal cortex (area 39) in association with aging. Capillary diameter in the parietal cortex was found to be increased age dependently. A similar age-related increase was also observed in the CA1 field but this age trend was not significant. Chronic treatment with the vincamines produced a dose-dependent reduction in intercapillary distance in senescent animals which approached the level of untreated adult control rats. Significant negative correlations were found between maze locomotion and intercapillary distance among senescent rats. Furthermore, intercapillary distance and local relative 2-deoxyglucose uptake tended to be negatively correlated in both age groups. These findings provide evidence for the working hypothesis that mean intercapillary distance can be considered as an indicator of neuronal activity in the pericapillary microenvironment.