Adjunctive drug therapy for treatment of experimental hydrocephalus

Abstract

We nvestigated two drugs, nimodipine and AXOKINE(R), and their effect on functional outcome in an infant rat model of experimental hydrocephalus. Hydrocephalus was achieved by injecting kaolin into the cisterna magna of three-week-old rats. Hydrocephalus was allowed to develop for two weeks prior to beginning treatment with nimodipine subcutaneously (1.8 mg per day) for 14 days at which time the rats were killed. The rats in this group were not surgically treated with shunting. In a separate experiment hydrocephalus was allowed to progress for three weeks. The rats were then shunted and intraventricular administration of a second generation ciliary neurotrophic factor, AXOKINE (R) at either a low dose (1.4 [mu]g/day) or high dose (14.3 [mu]g/day) was started. Functional assessment consisted of motor, memory and learning components. Motor function was tested using spontaneous activity counting, ability to stay on a rotating drum, and swimming. Memory and learning were quantitatively monitored using a modified Morris water maze. Histological examination provided pathological correlates to the functional outcome. (Abstract shortened by UMI.)