THE NEUROTOXICITY OF ALPHA-CHLOROHYDRIN IN RATS AND MICE .1. EVOLUTION OF THE CELLULAR-CHANGES

Mice and rats are found to be equally susceptible to developing symmet rical brain stem lesions on exposure to a-chlorohydrin and in both spe cies the earliest neurotoxic changes are strictly confined to glial ce lls, particularly astrocytes; haemorrhages are not found in either spe cies. Minimal evidence of increased vascular leakage of horseradish pe roxidase (HRP) in rats is shown by increased HRP content of perivascul ar cells within the lesions. Later macrophage invasion and capillary p roliferation is accompanied by rare focal leakiness of HRP. Gross astr ocytic damage, therefore, does not necessarily impair integrity of the blood-brain barrier. While early in intoxication, astrocytes are seve rely distended with fluid and their organelles seriously disorganized, they do not die but rapidly regenerate their processes. They thus app ear to undergo a process of 'clasmatodendrosis' from which they recove r. Comparisons are made with the genesis of symmetrical brain stem les ions in other acute energy deprivation syndromes, including Wernicke's encephalopathy.