Process of repair in the neuroepithelium of developing rat brain during neurogenesis: chronological and quantitative observation of DNA-replicating cells.

The neuroepithelium (NE) of the cerebrum of the developing brain has been reported to 'regenerate' within a certain period after being injured. To clarify the process of repair of the NE during neurogenesis, we chronologically examined the number of cells in the neocortex, and the rate of DNA-replicating cells and the mitotic figure ratio in the NE of rats after injury. The injury was induced by transplacental administration of ethylnitrosourea (ENU), which is cytotoxic immediately after administration, to the pregnant rats on embryonic day 16. The number of living and pyknotic cells in a 220-micron width of the neocortex was evaluated in each of three groups, such as NE, subventricular zone (SVZ) + intermediate zone (IMZ) + subplate (SP), and cortical plate (CP). The 5-bromo-2-deoxyuridine (BrdU)-labeling index and the mitotic index were examined 4, 8, 16, 24, 36, and 48 h after ENU administration. Up to 16 h after ENU administration, the number of living cells per 220 microns width in the NE and SVZ + IMZ + SP decreased, but increased in CP. From 16 to 24 h, the living cell number per 220 microns width in the NE and CP was unchanged, but increased in the SVZ + IMZ + SP. From 24 to 36 h, the living cell number per 220 microns width increased in all the groups, NE, SVZ + IMZ + SP and CP. From 36 to 48 h, the living cell number per 220 microns width in the NE was unchanged, but increased in the SVZ + IMZ + SP and CP. The BrdU-labeling index reached its nadir at 8 h, but markedly increased by 16 h, and then decreased to the control level by 36 h. No mitotic figures were observed at 16 h after administration, but a significant increase in mitotic index was noted at 24 h, and after which it decreased to almost the control value by 36 h. These findings indicate: (i) that temporary arrest of neuroepithelial cell cycle occurs in the G1-phase from 4 to 8 h after ENU administration, (ii) that the cell synchronizes in the S-phase at 16 h, (iii) that a proportion of neuroepithelial cells of rat fetal neocortex at the neurogenesis stage return to neuroepithelial cell proliferation stage, to repair the NE, and (iv) that regulation of the cell kinetics of neuroepithelial cells depends on the number of cells in a certain width of NE during regeneration.