Axial skeletal malformations associated with cranioschisis aperta and exencephaly. The result of experimental intervention after the neural tube closure in rats.

Maternal administration of a single dose of cyclophosphamide (20 mg/kg) after the neural tube closure (on day 12) resulted in exencephaly and cranioschisis in 100% of rat fetuses at term. Extensive hemorrhages and edema were regularly associated with these defects. Alizarin-red stained skeletal preparations revealed absence of skull vault, premature closure of basicranial synchondroses, exaggeration of the craniovertebral angle, and agencies and hypoplasia of the vertebrae, ribs and sternum. It is suggested that failure of the neural tube to close is not the primary cause of axial skeletal malformations and even after closure, the axial skeletal anlagen remains susceptible to teratogenic insult.