AGE-RELATED-CHANGES IN BRAIN MICROANATOMY - SENSITIVITY TO TREATMENT WITH THE DIHYDROPYRIDINE CALCIUM-CHANNEL BLOCKER DARODIPINE (PY-108-068)

The influence of aging and of treatment with the dihydropyridine Ca2antagonist darodipine (PY 108-068) on the age-related microanatomical changes of rat brain were studied in male Wistar rats treated from the 18th to the 24th month of age with an oral dose of 5 mg/kg/day of dar odipine. Twelve-month-old untreated rats were used as an adult referen ce group. A decreased number of nerve cells and of alkaline phosphatas e-positive capillaries and an increased lipofuscin deposition were obs erved in the frontal and occipital cortex, in the hippocampus, and in the cerebellar cortex of rats of 24 months in comparison with 12-month -old animals. The number of nerve cells was higher in the occipital co rtex and in the hippocampus, but not in the frontal cortex and in the cerebellar cortex, of darodipine-treated rats in comparison with age-m atched untreated animals. Lipofuscin deposition is reduced in all the brain areas investigated. The density of alkaline phosphatase-reactive capillaries is also increased in the frontal and occipital cortex and in the hippocampus of aged rats treated with darodipine. The above re sults suggest that treatment with darodipine is able to counter some m icroanatomical changes occurring in the brain of aged rats and involvi ng not only microvascular parameters. The occipital (visual) cortex an d the hippocampus were the cerebral areas more sensitive to treatment with darodipine. The possible relevance of these findings is discussed .