Arnold‐Chiari‐like malformation associated with a valproate model of spina bifida in the rat

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Abstract
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 structural changes similar to that seen for the Arnold‐Chiari malformation (ACM) in humans. Only fetuses exposed to the 1,200‐mg/kg level VA demonstrated spina bifida (SB) type widening of the vertebral arch when compared 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 such that the cerebellum was displaced toward the foramen magnum in a manner akin to human ACM. These findings indicate that valproate‐induced SB in the rat more closely approximates SB in humans than was previously appreciated and provides a model for experimental study of both SB and ACM.