Effects of Soman on Ultrastructure and Function of the Rat Blood-Brain Barrier

摘要

Soman, an organophosphate irreversible inhibitor of acetylcholinesterase, was studied for its effect on the rat blood-brain barrier (BBB) during the first 24 hours of intoxication. Young adult male Sprague-Dawley rats, injected with Evans blue-dye and surviving a subsequent single convulsive dose of soman presented focal and diffuse penetration of dye in areas of brain normally considered protected by the BBB. Brains of nonconvulsing animals and animals pretreated with nembutal or with diazepam were free of extravasated dye. A ranking of dye breached areas suggested that cerebellar and cerebral cortex hippocampus basal ganglia thalamus and hypothalamus brain stem. Ultrastructural analysis of breached brain regions with horseradish peroxidase as a tracer molecule, revealed that the probable subcellular mechanism of the induced breach was enhanced vesicular transport, a mechanism similarly described for seizure. Consequences of the breach were emphasized with the detection within the central nervous system of significantly elevated levels of an exogenously administrated quaternay compound, 3H-hexamethonium. These findings presented evidence that a soman-induced breach of the rat blood-brain barrier is convulsive dependent, demonstrates BBB mechanisms similar to that of seizure can allow CNS penetration of blood-borne drugs and circulatory proteins that normally would be slowed or excluded by an intact BBB. (KT)