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 rats, estimated with the hydrogen clearance method. Either a cholesterol (100 mg, as a control) or corticosterone (100 mg) bead was implanted subcutaneously in rats for a period of three months, beginning at 12 weeks of age. The effects of the treatments on the local circulation of the hippocampus were evaluated three to four months after the termination of the treatments. Hippocampal cerebral blood flow in corticosterone-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 neuropathological changes were characterized by soma shrinkage and condensation, or nuclear pyknosis, as reported previously. We concluded that a long-term glucocorticoid exposure resulted in an impairment of the hippocampal functions, accompanied by neuronal damage similar to that found in aged hippocampus. The present results support the hypothesis that glucocorticoids accelerate age-related changes in the brain.