The neurotoxicity of alpha-chlorohydrin in rats and mice: II. Lesion topography and factors in selective vulnerability in acute energy deprivation syndromes.
Mice and rats have been found almost equally susceptible to (R, S)-alpha-chlorohydrin neurotoxicity, but in rats the distribution of lesions in the neuraxis is less widespread. The topography of the brain lesions shows an incomplete relationship to the regional hierarchy of local glucose utilization in rats and local cerebral blood flow in mice, suggesting that other, unknown, factors also play roles in determining this. Evidence suggesting progressive tonotopic selective vulnerability was found in inferior colliculi in rats given five doses of 50 mg/kg/day. Distinct differences in the patterns of damage to brain stem centres found with chlorohydrin by comparison with other acute energy deprivation syndromes, despite the proximity of the metabolic lesions along the energy generation pathway, suggests there are other unrecognized factors that play a role in determining whether a neuronal centre is at risk or not.
Cavanagh
J B
JB
Toxicology Unit, Medical Research Council Laboratories, Carshalton, Surrey, UK.
Nolan
C C
CC
D000818:Animals; D001928:Brain Diseases, Metabolic / Q000473:pathology*; D001933:Brain Stem / Q000187:drug effects* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007888:Leigh Disease / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017208:Rats, Wistar; D014899:Wernicke Encephalopathy / Q000473:pathology; D000517:alpha-Chlorohydrin / Q000494:pharmacology*
D000517:alpha-Chlorohydrin