Congenital hydrocephalus mimicking Dandy-Walker syndrome induced by 6-aminonicotinamide injection in pregnant rat

Abstract

Fetal hydrocephalus was induced by single intraperitoneal injection of 8 mg/kg 6-aminonicotinamide (6-AN), a niacinamide antagonist, in Sprague-Dawley rat on day 13 of gestation. Materials for histological examination were obtained by uterotomy 1, 2, 4, and 8 days after injection, and untreated fetuses of the same ages were used as controls. Macrocephalus was clear at day 17 (4 days after injection), when cerebral dysgenesis was suggested by bromodeoxyuridine immunohistochemical study. The entire ventricular system was dilated, including the aqueduct and foramen of Monro, and hypoplasia of the cerebellum was also observed. On day 21, macrocephalus was remarkable, and considerable hypoplasia of the choroid plexus and cerebellum and agenesis of the corpus callosum were recognized. These results indicate that this experimental hydrocephalic model associated with various central nervous system anomalies mimics human Dandy-Walker syndrome, suggesting the pathogenesis of Dandy-Walker syndrome to be a feature of systemic metabolic deficits.