Tissue repair in the embryonic rat spinal cord following exposure to N-ethyl-N-nitrosourea

The cytotoxic effects of N-ethyl-N-nitrosourea (ENU) and the potential for recovery from this damage in the developing rat spinal cord was investigated. Emphasis was placed on determining the severity and location of initial cell necrosis and the subsequent reorganizational changes in the damaged tissues. Pregnant rats were injected i.v. with a single dose of ENU (60 mg/kg) on one of days 12-16 of gestation. At 6, 12, 24 and 48 h post-injection one pregnant rat from each gestational stage was anesthetized, the embryos were removed, fixed and processed for embedding in paraplast or epon-araldite. Transverse sections from embryos killed at 6 h revealed extensive necrosis throughout the neuroepithelium in accordance with the temporal-spatial patterns of neurogenesis. At this dose level the post-mitotic neuroblasts appeared unaffected. Regeneration of the damaged neural tissue as defined by the restoration of the neuroepithelial cell layer and removal of necrotic debris proceeded quickly, and within 48 h a near-normal cytoarchitecture was observed. The embryonic age at time of ENU injection had no apparent influence on the actual sequence of tissue repair in the spinal cords although the events were slightly delayed within embryos exposed to ENU on days 12 or 13 of gestation.