Exencephaly is said to precede anencephaly resulting from failure of the rostral 
neuropore closure. In order to verify if the exencephaly induced after neural 
tube closure would also lead to anencephaly, exencephaly was induced in rat 
fetuses by maternal administration of a single dose (15 mg/kg) of 
cyclophosphamide on day 12 of gestation and pregnancy was prolonged by uterine 
ligation until postconception (PC) day 24. Fetal death was found to increase 
with prolongation of gestation and no sign of recovery from growth retardation 
was observed. Alizarin red-S-stained skeletal preparations substantiated the 
persistence of skull malformations in the exencephalic fetuses. Histological 
observations of the mesenchyme and the brain indicated degenerative changes that 
were intensifying with time. The ventricular system expanded progressively; the 
ependyma was denuded and neural mass lay free in the ventricle. The choroid 
plexus appeared to be elaborate and extensive. The haemorrhagic capillary 
network around the brain tissue was highly proliferative and appeared to 
penetrate the former from the exterior. Tissue necrosis seemed to progress 
unabated. Cystic spaces appeared beneath the base of the brain and became 
progressively large and it appeared as if the brain was being pushed out of the 
shallow cranial fossae. By PC day 24, most of the brain tissue had degenerated, 
thus giving clearly the appearance of the anencephalic condition.