Ultrastructural changes in isoniazid-induced brain oedema in the dog.

Dogs dosed daily with isoniazid, 15 mg kg 1 for 45 and 69 days or 2o-4o mg kg -1 for 4-2o days, showed; 'vacuolation' of myelin, astrocyte hypertrophy and oligodendrocyte degeneration. The distribution of vacuolation was different in lowand high-dose animals. The vacuolation seen with the light microscope resulted from splitting of the intraperiod line, dilatation of the periaxonal space, distension of the inner tongue of oligodendrocyte cytoplasm and focal axonal swelling. In addition to degenerative changes in the cell body region of oligodendrocytes pyknotic nuclei, loss of polysomes, mitochondrial enlargement and ceil swelling abnormalities in the appearance of the inner tongue of oligodendroycte cytoplasm occurred. Evidence of demyelination and remyelination was found in the long term animals. In the high-dose animals, focal areas of expanded extracellular space as well as evidence of damaged blood vessels, were seen in the cerebral cortex. It could not be determined if these changes represented early lesions or resulted from perfusion artefact. Attention is drawn to a number of conditions in which astrocytic hypertrophy and myelin 'vacuolation' occur together.