6-Aminonicotinamide-induced hydrocephalus in suckling mice

Following a single intraperitoneal injection of 6-aminonicotinamide (6-AN, 50 mg/kg of body weight) into newborn mice of the Institute of Cancer Research strain, hydrocephalus consistently developed nine days after injection, with rapid progression. All of these mice died before reaching adulthood. The most striking early histologic change in these mice was cytoplasmic vacuolation of ependymal cells, which was observed as early as 24 hours after injection. Vacuolation of subependymal astrocytes appeared during the next few days. After day seven, the aqueduct was obliterated by swollen vacuolated ependymal cells and subependymal astrocytes. The aqueduct remained obliterated even after the vacuolation of the ependymal cells subsided after day nine, when vacuolation of subependymal astrocytes was still pronounced. These morphological observations reveal that, in newborn mice, the ependymal cells are the most sensitive to the toxic action of 6-AN and suggest that the pathogenesis of 6-AN-induced hydrocephalus is likely to be due to the combination of ependymal cell damage and compression of the lumen by the edematous periaqueductal gray matter. This is a highly reproducible animal model of drug-induced hydrocephalus.