Morphometric evaluation of degenerative and regenerative changes in isoniazid-induced neuropathy

Morphometric studies of the pathologic changes were carried out on the peripheral nerves, spinal roots, and different levels of the Goll's tract in rats given isoniazid and killed 1, 2, 3, 4, 5, 6, 7, 14, and 30 days after intoxication. In teased fiber preparations, axonal degeneration was the main change present, and this was seen as early as day 2 in the peroneal and distal sural nerves. The frequency of myelinated fibers showing axonal degeneration was higher in the distal than the proximal sural nerve, and in the ventral than the dorsal root. In the group of rats killed on 5, 6, 7, and 14 days, a significant decrease of the myelinated fiber density was observed in the distal and proximal sural nerves, ventral root, and at the third cervical level of the Goll's tract. The degree of fiber degeneration was more severe in the distal than in the proximal sural nerve and in the third cervical than the fifth thoracic level of the Goll's tract. Preferential decrease of large myelinated fibers was noted in all the affected nerves. No definite abnormalities, however, were seen in nerve cells of the 6th lumbar spinal ganglia and anterior horn cells of the lumbar spinal cord on light microscopy. On 30 days, regeneration at varying degrees was discerned in all the affected nerves with significant increase of small myelinated fibers, particularly in the ventral root. The findings indicate that both centrally and peripherally directed myelinated axons are more affected in the distal than in the proximal segments while the neuronal cell bodies are spared. The spatio-temporal evolution of this pattern of change is compatible with the concept of the "dying back" process or central-peripheral distal axonopathy.