ARNOLD-CHIARI-LIKE MALFORMATION ASSOCIATED WITH A VALPROATE MODEL OF SPINA-BIFIDA IN THE RAT

The brains of rat fetuses exposed to saline and valproic acid (VA: 600 mg/kg or 1,200 mg/kg) at 10 days of gestation were examined for struc tural changes similar to that seen for the Arnold-Chiari malformation (ACM) in humans. Only fetuses exposed to the 1,200-mg/kg level VA demo nstrated spina bifida (SB) type widening of the vertebral arch when co mpared to saline treated animals. When compared to controls, both 600- and 1,200-mg/kg VA animals demonstrated microencephaly. The brains of treated animals demonstrated alterations in their angular morphology s uch that the cerebellum was displaced toward the foramen magnum in a m anner akin to human ACM. These findings indicate that valproate-induce d SE in the rat more closely approximates SE in humans than was previo usly appreciated and provides a model for experimental study of both S E and ACM. (C) 1995 Wiley-Liss, Inc.