LONG-TERM GLUCOCORTICOID TREATMENTS DECREASE LOCAL CEREBRAL BLOOD-FLOW IN THE RAT HIPPOCAMPUS, IN ASSOCIATION WITH HISTOLOGICAL DAMAGE

The present study examined the influence of a long-term treatment with glucocorticoid on local cerebral blood flow of the hippocampus in rat s, estimated with the hydrogen clearance method. Either a cholesterol (100 mg, as a control) or corticosterone (100 mg) bead was implanted s ubcutaneously in rats for a period of three months, beginning at 12 we eks of age. The effects of the treatments on the local circulation of the hippocampus were evaluated three to four months after the terminat ion of the treatments. Hippocampal cerebral blood flow in corticostero ne-treated rats was significantly lower (P<0.05) than that in control rats, and fluctuated over a day in lower amplitude than the controls. Severe histological damage was observed in the CA1 and CA3 cell fields of the hippocampus in corticosterone-treated rats. These neuropatholo gical changes were characterized by soma shrinkage and condensation, o r nuclear pyknosis, as reported previously. We concluded that a long-t erm glucocorticoid exposure resulted in an impairment of the hippocamp al functions, accompanied by neuronal damage similar to that found in aged hippocampus. The present results support the hypothesis that gluc ocorticoids accelerate age-related changes in the brain. (C) 1997 IBRO . Published by Elsevier Science Ltd.