Evolution of axonal swellings in cats intoxicated with beta,beta'-iminodipropionitrile (IDPN). An electrophysiological and morphological study.

beta,beta'-Iminodipropionitrile (IDPN) causes formation of axonal swellings in the proximal internodes of spinal motor axons. The swellings enlarge and demyelinate with the progression of the neuropathy. The correlation between axonal swellings and electrophysiologic function of motoneurons was examined in cats 2 to 35 days after initial administration of IDPN. Morphologic changes in intraspinal motor axons, occasionally observed 2 days after the first injection, became progressively more evident at later times, with enlargement at the first internode in some axons and appearance of fusiform or balloon-like axonal swellings. At 7 days axonal swellings were infrequently observed and the main structural feature was a reduction in myelin thickness in affected nerve fibers. Despite scant histopathologic changes, motoneuron action potential discharge at this time was significantly altered in latency to onset of spike and rate of rise. Abnormal motoneuron firing patterns were observed at this time. As the neuropathy progressed, both the frequency of occurrence and the size of axonal swellings increased markedly but at no time was there morphologic evidence of chromatolysis. At 14 and 35 days, (after two or five IDPN injections) action potential discharge became further altered in latency to spike onset, rate of rise, initial segment conduction time and somal-dendritic threshold. The incidence of repetitive firing increased and axonal conduction block was observed in several motoneuron recordings. The electrophysiologic changes closely resemble those reported in chromatolytic motoneurons after axotomy. The axonal swellings induced by IDPN may produce an axotomy-like condition which becomes more prominent as the neuropathy progresses but without morphologic evidence of chromatolysis.