Early neurovascular abnormalities underlying 6‐aminonicotinamide (6‐AN)‐induced congenital hydrocephalus in rats

Abstract

Abstract Defects in the rat central nervous system during retarded brain development and congenital hydrocephalus were studied following single maternal injections of the niacinamide antimetabolite 6‐aminonicotinamide (6‐N) late in development. Histological and histochemical analyses indicated CNS hemorrhage and growth retardation of fetal brains 24 hours after treatment; fluid movement into cerebral ventricles was evidenced by secretionlike, circular “blebs” along the ependymal lining. There was transitorily increased glycogen in hypoplastic choroid plexuses with disruption of cerebral layering of neuroblasts. Despite thinned cerebral cortex and increased ventricular surface area, associated with cranial distortion and communicating, compensatory ventricular enlargement, normal intracranial pressure was recorded by day 21 of gestation. During the pathogenetic process macrophagic cells removed cellular debris and RBC's so that by term little evidence of early hemorrhage was apparent.