EFFECTS OF PARAPLEGIA PRODUCED BY INTRATHECAL 6-AMINONICOTINAMIDE ON MOTOR UNITS IN THE RAT

An intrathecal injection of 6-aminonicotinamide (6-AN) in adult rats produced a central myelopathy with destruction of neurons and gliosis. After a latent period of 24 to 36 h, the animals developed flaccid paralysis of the hind limbs, followed by irreversible hypertonic paraplegia. Motor nerve conduction velocities in the tibial nerve of 6-AN-treated animals (serial recordings 3-550 days) were the same as controls and teased nerve fibers to extensor digitorum longus (EDL) and soleus muscles showed no evidence of nerve regeneration. In vivo studies of contractile properties of 6-AN-treated soleus showed that the mean maximal twitch and tetanic tensions were greatly reduced compared to controls by 14 days. The same occurred in the 6-AN-treated EDL, but to a lesser degree. These changes in contractile properties persisted throughout the 570-day period of observation. There was no significant change in the percentage of fiber types in the soleus muscles after 6-AN. However, the EDL had an increased number of type I fibers by 30 days and this peaked at 90 days and was associated with a decrease in type IIC and IIA but not IIB fibers. Initially the type I fibers occurred at random, but by 2 to 3 months, they occurred in small groups of 5 to 20 fibers. The mean areas of all fibers were reduced as early as 2 weeks in both 6-AN-treated EDL and soleus muscles. These changes most likely resulted from the chronic hypertonic paraplegia with extensor posturing, followed by immobilization at knee and ankle joints and loss of some spinal motoneurons with peripheral sprouting, especially of type I motoneurons. © 1979.