On the role of seizure activity in the hippocampal damage produced by trimethyltin.
Trimethyltin (TMT) causes a pattern of hippocampal damage in rats that is similar to that caused by convulsant chemicals or seen in the brains of some human epileptics. Therefore, we investigated the possible role that TMT-induced seizure activity might play in the hippocampal damage produced by this organotin. The morphologic effects of systemically administered TMT were compared to those of kainic acid given by the same route. Unlike kainate, TMT produced seizures in only a subset of treated animals and with a latency of days rather than minutes. Evaluation of morphology during the acute seizure period revealed that TMT-induced seizures were associated with a variable pattern of granule and pyramidal cell necrosis and acute dendritic swelling in the two associational/commissural hippocampal pathways, one from CA3 to CA1-CA3 and the other from the hilus to the proximal dendrites of dentate granule cells. The TMT-induced damage contrasted sharply with the acute pattern of kainate-induced damage that consisted of acute dendritic swellings in the distal granule cell dendrites, hilus and mossy fiber region. TMT-treated rats that did not exhibit seizures in the one week after injection exhibited minimal pathology during this period. These results suggest that at least part of the damage to granule and pyramidal cells produced by TMT is mediated by the seizure activity produced by this compound. Although the resulting lesions to the CA1-CA3 pyramidal cells may appear similar in both TMT- and kainate-treated rats long after injection, evaluation of acute pathology during the active seizure phase indicates that these compounds induce seizure activity in different hippocampal pathways and cause different patterns of irreversible neuronal damage as a result.
Sloviter
R S
RS
von Knebel Doeberitz
C
C
Walsh
T J
TJ
Dempster
D W
DW
D000818:Animals; D001927:Brain Diseases / Q000139:chemically induced / Q000473:pathology; D006624:Hippocampus / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced* / Q000473:pathology; D014220:Trialkyltin Compounds / Q000633:toxicity*; D014298:Trimethyltin Compounds / Q000633:toxicity*
D014220:Trialkyltin Compounds; D014298:Trimethyltin Compounds; C037718:trimethyltin hydroxide