CYANIDE LEUCOENCEPHALOPATHY IN RATS AND OBSERVATIONS ON THE VASCULAR AND FERMENT HYPOTHESES OF DEMYELINATING DISEASES

Abstract

150 rats were treated subcut. 1-40 days with sterile KCN. Daily dosage averaged 2-6 mg. and was just sublethal, being increased as soon as it became no longer lethal for the surviving animals. Nearly 100 died in the first 2 wks. but only 1 had a cerebral lesion, a condition which appeared in 16 of the 37 rats surviving 2 wks. to 6 mos. The lesions start in the callosal commissure, the more advanced involving all of it and sometimes the hippocampal commissure. Histologically they resemble plaques of disseminated sclerosis, but are of less abrupt contour and have peripheral fenestration. The demyelination is selective. There is paucity of astroglial reaction and no thrombosis. Exptl. cerebral capillary embolism was produced in about 150 rats by carotid injn. of sterile cod liver oil, causing lesions widely dispersed throughout the hemisphere. These showed quick, intense microglial reactions, numerous fat granule cells and, later, mesodermal scar formation with macrophages. Similar injn. of quinine and urethane in 100 animals produced minute scattered mesencephalic softenings in contrast to the embolic lesions which were located in the cerebral cortex, cornu ammonis and hippocampus. Exptl. CO poisoning was produced daily in 31 rats for 3 wks. and repeated with 7- to 10-day intervals between treatments for as long as 3 mos. In 3 animals this produced multiple tiny foci of microglial reaction in the cerebral cortex, caudate nucleus, cerebellum and spinal cord. It is concluded that degeneration of white matter induced by cyanide proceeds sui generis; that the demyelinating diseases are caused by the liberation, within the brain substance itself, of a myelinolytic ferment.