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Neuropathological studies on cycloate-induced neuronal cell death in the rat brain.

Abstract：

:The herbicide cycloate (carbamothioic acid, ethyl(cyclohexyl)-S-ethyl ester) given as a single oral dose to rats, caused selective neuronal cell death in two regions in the rat forebrain, the pyramidal neurons of layers II-III throughout the pyriform cortex and in granule cells of the caudal ventro-lateral dentate gyrus. Male Alderley Park rats, 6-8-week-old, were given a single oral dose of either 0 or 2000 mg/kg cycloate and killed for neuropathological investigation 1, 2, 3, 7, 14 or 28 days after dosing, using a regime of perfusion fixation with modified Karnovsky's fixative, followed by routine paraffin embedding. Seven transverse levels of brain were examined from each rat. Cycloate-induced neuronal cell death was seen in the pyriform cortex 1 day after dosing and persisted through to Day 28, the lesion was more marked in the rostral compared to the caudal region of the pyriform cortex. Neuronal cell death was also observed in the ventro-lateral caudal dentate gyrus on Days 1-14, day after dosing. In the early stages, Days 1-3 and to a lesser extent Day 7, the neuronal cell death resembled apoptosis, characterized by condensation of nuclear material, cell shrinkage and strong cytoplasmic eosinophilia. By Days 14 and 28 and to a lesser extent Day 7, the cell death resembled necrosis, i.e. karyorrhectic nuclei with pale irregular cytoplasm. Microglial accumulation was associated with the neuronal cell injury. In control brains, an occasional apoptotic body was seen in both the pyriform cortex and dentate gyrus. Our results demonstrate that cycloate is a novel neurotoxicant, which following a single large oral dose induces a cell specific and highly localized forebrain lesion. The time course data analyzed temporally, suggests that cycloate may cause an up regulation of apoptosis in selected regions of the adult brain.

journal_name

Neurotoxicology

journal_title

Neurotoxicology

authors

Simpson MG,Horner SA,Mistry P,Duffel S,Widdowson PS,Scanlon Y,Lock EA

doi

10.1016/j.neuro.2004.07.006

subject

Has Abstract

pub_date

2005-01-01 00:00:00

pages

125-32

issue

1

eissn

0161-813X

issn

1872-9711

pii

S0161-813X(04)00107-X

journal_volume

26

pub_type

杂志文章

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