title: Light microscopic studies on the pathogenesis of exencephaly and cranioschisis induced in the rat after neural tube closure.
abstract: Administration of a single dose of cyclophosphamide (20 mg/kg) to Charles Foster (CF) rats on day 12 of gestation (i.e., well after neural tube closure) results in exencephaly in almost 100% of living fetuses at term (Padmanabhan, '84). Following the same treatment, embryos/fetuses were collected at various intervals of time (from 8 hr to day 19 of gestation) and studied histologically. At 10 hr after treatment, the neuroepithelium (NE) of the brain vesicles and the neural crest-derived ganglia exhibited pronounced cell death. By day 13, cell death appeared to be more intense and extensive in the NE; the mesenchyme (ME) was less proliferative and was loosely organized. In the following days, the NE presented vacuolizations which coalesced into cavities; these cavities were often bilaterally symmetrical, contained free neuroblasts and erythrocytes, and subsequently opened into the ventricles. The choroid plexus hypertrophied, the ventricles distended, and the NE gradually became very thin. The hypertrophied capillaries of the ME cleaved through the NE, thus delaminating an outer stratum. Subcutaneous blebs developed over the brain vesicles and communicated with the cavities in the brain. Thus the ventricles and the blebs came into direct communication. The ME dorsal and lateral to the brain was loose, and at no site was it organized into the skull primordium. By day 19, there were clear and multiple discontinuities in the walls of the brain. Initial cell death and vacuolization in the NE, inhibition of ME proliferation followed by hypertrophy of the choroid plexus, and possibly enhanced intraventricular pressure and hemorrhage and edema of the ME seem to underlie this process of reopening of the closed neural tube.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Anatomy, Faculty of Medicine, Kuwait University, Safat.
authors.forename: R
authors.initials: R
authors.lastname: Padmanabhan
mesh_terms: D000818:Animals; D001921:Brain / Q000002:abnormalities* / Q000196:embryology / Q000473:pathology; D003520:Cyclophosphamide / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D012886:Skull / Q000002:abnormalities* / Q000196:embryology / Q000473:pathology; D013723:Teratogens
chemical_list: D013723:Teratogens; D003520:Cyclophosphamide