Neuropathology of trimethyltin: a proposed pathogenetic mechanism.

The pathological changes in the limbic system induced by trimethyltin (TMT) in mouse, rat, and neonatal rats were reviewed and compared. It becomes apparent that there was an inverse pathological pattern between the fascia dentata granule cells and the Ammon's horn CA3 pyramidal neurons. This inverse pathological relationship could be demonstrated along the septotemporal axis of the adult brain as well as in neonatal nervous system. Thus it becomes apparent that the induction of pathological lesion in the Ammon's horn requires the functional integrity of the granule cells. The hypothesis of "hyperexcitory" and "hyperstimulatory" damage of neurons was proposed. In view that this inverse relationship also exists between the entorhinal cortical cells and the fascia dentate granule cells as well as between the CA3 and CA1,2 neurons in the Ammon's horn, a theory on the hyperexcitory cascade between the entorhinal cortex----fascia dentate----CA3----CA1,2 neurons was constructed. The present proposal represents a working hypothesis which helps to explain the various patterns of pathological lesions induced in the nervous system by TMT.