I Wyatt

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The discovery that the herbicide paraquat was selectively accumulated by the lung, both in vivo and in vitro, in comparison with other tissues, provided an explanation for its selective toxicity to the lung. This uptake process is energy dependent and obeys saturation kinetics. A characterization of the process led to the identification of endogenous(More)
Cultured cerebellar granule cells and cerebellar slices from neonatal rats have been widely used to examine the biochemistry of excitatory amino acid-induced cell death mediated in part by the activation of NMDA receptors. However, the NMDA subunit stoichiometry, producing functional NMDA receptors is different in cultured granule cells, neonatal and adult(More)
Daily oral administration of 2.3 mmol/kg L-2-chloropropionic acid (L-2-CPA), DL-2-bromopropionic acid (2-BPA) or DL-2-iodopropionic acid (2-/PA) but not DL-2-fluoropropionic acid (2-FPA) produced cerebellar granule cell necrosis in the rat. Twenty four hours after three doses of L-2-CPA or two doses of 2-BPA, animals showed clinical signs of motor(More)
L-2-Chloropropionic acid (L-2-CPA) selectively damages the cerebellum in adult rats. The rat cerebellum continues to develop postnatally during the first 4 weeks of life. In this study we examined the neurotoxic effect on rats of increasing postnatal age. Daily oral dosing of rats aged 56 days with 250 mg/kg per day of L-2-CPA for 3 days produced necrosis(More)
We have used the model of L-2-chloropropionic acid (L-CPA)-induced selective cerebellar granule necrosis to study excitatory amino acid-induced necrotic cell death in vivo produced by the activation of N-methyl-D-aspartate (NMDA) receptors. However, the mechanism for the NMDA receptor activation and the biochemical events which dictate the anatomical(More)
Administration of a single oral dose of 750 mg/kg L-2-chloropropionic acid (L-CPA) to rats produces marked necrosis to the granule cell layer of the cerebellum by 48 h after dosing. Associated with the neuropathology the rats show locomotor impairment and a loss of body weight and a significant increase in cerebellar water and sodium content, indicating an(More)
1. L-2-Chloropropionic acid (L-CPA) is neurotoxic when administered orally as a neutral sodium salt in high doses to rats, resulting in a selective destruction of cerebellar granule cells with the result that animals develop marked difficulties in maintaining normal locomotion. 2. Cerebellar granule cell destruction is accompanied by a reduction in(More)
L-2-Chloropropionic acid (L-CPA), when orally administered at single high dose to rats produces a selective lesion in the cerebellum involving destruction of a high proportion of granule cells by a mechanism which involves N-methyl-D-aspartate (NMDA) receptors. Receptor binding studies demonstrated that L-CPA a had low affinity at the glutamate and glycine(More)
1p4studied the effect of L-2-chloropropionic acid (L-CPA)-induced (250 mg/kg/po/day for 3 days) neurotoxicity, which results in an almost total destruction of cerebellar granule cells over 5 days, on forebrain and cerebellar neurochemistry. There was a reduction in cerebellar aspartate and glutamate concentrations of L-CPA-treated rats and a reduction in(More)
We have demonstrated that following a single oral dose of L-2-chloropropionic acid (L-CPA) to rats (750 mg/kg; pH 7) there was a marked and widespread loss of granule cells in the cerebellum as assessed by neuropathology by 48 hr. There also appeared to be limited damage to Purkinje cells, whereas stellate, Golgi, and basket cells were not affected by L-CPA(More)