Enhancement of the Anticonvulsant Action of Acetazolamide after Head X-Irradiation and Its Relation to Blood Brain Barrier Changes

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Abstract
The anticonvulsent action of acetazolamide is enhanced with respect to potency, time of onset, and duration of action in rats given (10,000 r) to the head. This effect of acetazolamide was maximal 48 hours postirradiation, In irradiated animals, stimulation of the sensorimotor cortex elicited only mild seizure discharges. Evoked discharges were completely suppressed by a dose of acetazolamide ineffective in control animals. Penetration of S35-acetazolamide in-reased in 4 discrete anatomical regions of the brain; cerebral cortex, hypothalamus, hippocampus, and cerebellar cortex. Increase in brain drug content was temporally related to the pharmacolohical effects manifest in the irradiated animal. It is concluded that head x-irradiation induced subtle and selective BBB permeability changes, permitting an increased selective penetration into the brain of the normally slow penetrating drug, acetazolamide.