The time-course of trimethyltin-induced fiber and terminal degeneration in hippocampus.

Trimethyltin (TMT) produces prominent neuron death in the hippocampus. The time-course of TMT-induced damage was studied using reduced-silver procedures for impregnation of degenerating axons and their terminals, and a modified Timm's stain procedure for visualization of hippocampal transitional metals. Standard cell body stains were also used. Fifty-four, adult, Long-Evans rats were gavaged with 6.0 mg TMT/kg b.wt. and 10 rats were gavaged with distilled water as controls. Five TMT-gavaged rats and one saline-gavaged rat were sacrificed on either postgavage day 1, 3, 6, 9, 14, 19, 30, 45, 70 or 99. Histological examination revealed a band of degenerating terminals in the stratum lucidum, below the hippocampal subfields CA3a,b pyramidal cells, by postgavage day 3. This preceded dentate gyrus granule cell loss supplying the mossy fiber input to the stratum lucidum by several days. Hippocampal pyramidal cell necrosis continued through the examination period while dentate granule cell loss subsided between postgavage days 9 and 14. Fiber and terminal degeneration was more extensive in the dorsal hippocampus than in the ventral hippocampus, although Timm's-stained sections revealed "bleaching" of stainable metal in the mossy fiber pathway of the ventral hippocampus. These data suggest that loss of ventral dentate granule cells might reduce TMT-induced necrosis of pyramidal cells in the ventral (temporal) part of the Ammon's horn, possibly by preventing the spread of seizure activity in this region of the hippocampus. Additionally, although previous studies have reported the toxic effects of TMT to last approximately 60 days, the results of the present study indicate that TMT-induced degeneration continues for more than 3 months. Reduced-silver stains, such as the Fink-Heimer procedure, appear to be more sensitive indicators of enduring neuropathology than more traditional cell stains.