AGE-DEPENDENT ALTERATION IN REGIONAL CEREBROVASCULAR PERMEABILITY DURING DRUG-INDUCED EPILEPSY

Abstract

Age-related changes in blood-brain barrier permeability were investigated during pentylenetetrazol-induced seizures in rats aged from 15 days to 120 days. Tracers such as [C-14]sucrose and [H-3]inulin which diffuse very slowly across the intact endothelium were simultaneously injected i.v. in rats treated with pentylenetetrazol (PTZ) or in control animals. Permeability-surface area products (PA) were determined in 9 brain regions. Pentylenetetrazol-induced seizures caused a significant increase in PA for both sucrose and inulin in all brain regions studied. Blood-brain barrier dysfunction was present only in animals in which the mean arterial blood pressure rose at seizure onset. Although increased blood-brain barrier permeability was found partly in similar areas in both young and adult rat brains, in adults the increase was the highest in the preoptic area, septum, colliculus inferior, hypothalamus and in the cerebellum while the increase was comparatively much smaller in the same areas of young brains. The increase in blood-brain barrier permeability was extremely high in the hippocampus, hypothalamus and cerebellum of 15-day-old rat brain and, was least affected in the corpus striatum and cerebral cortex in contrast to older rats. From the results obtained it may be concluded that the increased cerebrovascular permeability induced by pentylenetetrazol differs markedly in localization in young and adult rats. The age-dependent increased blood-brain barrier integrity is not over all dependent on variations in the blood pressure, but rather on progressive maturation of capillaries and changes in their internal structure, and local phenomena in neuronal activity during the seizures.