A time-course study of trimethyltin induced neuropathology in rats

The extent and time course of trimethyltin (TMT) induced lesions in the rat nervous system was studied. Adult Long-Evans rats were treated with a single dose of 6.0 mg TMT/kg b.w. and were sacrificed at 8 hours, 3, 15, 30 or 60 days following exposure. Histopathological examination of the brains revealed that neurons in the pyriform/entorhinal cortices and in the olfactory tubercle were extremely sensitive to TMT toxicity showing significant necrotic changes 3 days after exposure. Extensive neuronal loss and astrogliosis were observed 15 days after intoxication. In the hippocampal formation, the granule cells of fascia dentata showed early changes; however, evidence of toxic destruction in this area was not extensive and subsided considerably by the 3rd week of intoxication. On the other hand, destruction of the pyramidal neurons in Ammon's horn became more pronounced throughout the experimental period, resulting in extensive cell loss in this structure. It is interesting to note that the CA3 neurons in the anteromedial (septal) portion of the Ammon's horn appeared to be more vulnerable than those located more laterally (temporally), while the reverse pattern was observed for the CA1,2 neurons. Large mesencephalic trigeminal neurons in the brain stem also showed early chromatolytic changes. Since total normal morphology of these neurons was observed at later posttreatment time without apparent neuronal loss in these areas, total recovery of these nerve cells could be postulated.