Distinctive expression of midkine in the repair period of rat brain during neurogenesis: immunohistochemical and immunoelectron microscopic observations.

Distinctive expression of midkine (MK) was observed during the repair period of fetal brain neuroepithelium. MK is a heparin-binding growth factor that occurs as a product of a retinoic acid-inducible gene, and has a molecular mass of 13 kDa. MK expression was examined immunohistochemically and by immunoelectron microscopy during a period of repair in developing rat brain at the neurogenesis stage. Injury was induced in rat fetuses by transplacental administration of ethylnitrosourea (ENU) on embryonic Day (E) 16, and histological changes were examined up to 48 hr thereafter (i.e., up to E 18). In normal rat fetuses, MK immunostaining was observed in the cytoplasm and radial and horizontal processes of all cells in the neuroepithelium (NE), subventricular zone (SV), and intermediate zone (IMZ). In ENU-administered brains, cells in the NE, SV, and IMZ were damaged severely, especially 16-24 hr after ENU administration. The remaining neuroepithelial cells, with the exception of those in M-phase and the tips of processes at the ventricular surface, were negative for MK immunohistochemistry 16-24 hr after the administration of ENU. Forty-eight hours after the administration, the cytoplasm and processes of cells in the NE, SV, and IMZ were MK immunopositive. Our previous data reported that the cell cycle of most NE cells is synchronized to the S-phase 16 hr after ENU administration and to the M-phase at 24 hr, and many NE cells were recovered 48 hr after ENU administration. The previous results taken together with the present results indicate that: (1) MK expression does not increase during the repair period of the NE, being different from adults; (2) MK expression is likely to be suppressed at S-phase according to the condition of the NE; and (3) MK expression is not essential for every cell cycle phase of NE cells; but (4) is necessary to maintain the M-phase of NE cells. Copyright 2004 Wiley-Liss, Inc.