The neurotoxicity of alpha-chlorohydrin in rats and mice: I. Evolution of the cellular changes

Mice and rats are found to be equally susceptible to developing symmetrical brain stem lesions on exposure to alpha-chlorohydrin and in both species the earliest neurotoxic changes are strictly confined to glial cells, particularly astrocytes; haemorrhages are not found in either species. Minimal evidence of increased vascular leakage of horse-radish peroxidase (HRP) in rats is shown by increased HRP content of perivascular cells within the lesions. Later macrophage invasion and capillary proliferation is accompanied by rare focal leakiness of HRP. Gross astrocytic damage, therefore, does not necessarily impair integrity of the blood-brain barrier. While early in intoxication, astrocytes are severely distended with fluid and their organelles seriously disorganized, they do not die but rapidly regenerate their processes. They thus appear to undergo a process of 'clasmatodendrosis' from which they recover. Comparisons are made with the genesis of symmetrical brain stem lesions in other acute energy deprivation syndromes, including Wernicke's encephalopathy.