[Experimental studies on the etiological mechanism of congenital microcephaly].

Pregnant mice were injected intraperitoneally on different gestational day with either one or three successive doses of 30 mg/kg of cytosine arabinoside (ara-C), which has been known to interfere with DNA synthesis. Some of them were injected intraperitoneally with tritiated thymidine (3H-TdR) consecutively. The fetuses and the youngs were sacrificed at various hours and days after treatment. Pyknotic nuclei or nuclear debris were observed at the matrix layer three hours after the injection of single dose of ara-C. Nuclear debris were increased as time elapse and they were most prominent 12 hours after treatment. However, 24 hours later, new matrix layer was regenerating. Twenty-four hours after treatment with two successive doses of ara-C, labeling index in the matrix layer was about one third of that of control. Cerebral hemispheres of the treated youngs were reduced in size. The youngs, treated with three successive doses of ara-C on day 13, 14 and 15 of gestation, showed most severe microcephalus. Cytoarchitecture in the cortices of these microcephalic mice was characterized by irregular arrangement of the pyramidal neurons and their dendritic branches. Autoradiographic study revealed that cortical neurons which were produced at the regenerated matrix layer after ara-C treatment migrated to the surface of the cortex.