Experimental induction of cranioschisis aperta and exencephaly after neural tube closure. A rat model.

Administration of single doses of cyclophosphamide to pregnant rats on days 12-14 of gestation (i.e. well after closure of the neural tube) resulted in cranioschisis and exencephaly in 100% of fetuses observed at term. In these fetuses the brain was covered by atrophic epidermis devoid of skin appendages and a highly vascular loose mesoderm without the osseous skull vault and the meninges. There were obvious hemorrhages in the brain tissue and in the ventricles. The thin walls of the distended ventricles showed breaks through which the ventricles communicated with the exterior and with the cavities in the brain. The choroid plexus had hypertrophied and denuded neuroepithelium could be found in the ventricles. Associated anomalies included edema, hemorrhage, exophthalmia, micrognathia, defects of the skull base, an increase in the basiocranio vertebral angle, reduction deformities of the limbs, etc. Chronological observations indicated a progressive distension of the ventricular system of the brain. A very high incidence of cranioschisis and exencephaly and the consistency of associated pathology validate the point that this is an excellent experimental model for investigating the pathogenetic mechanisms of these serious malformations.