Effects of 2,5-hexanedione on rat spinal pyramidal tract

The present study was undertaken to investigate central axonal neuropathy caused by 2,5-hexanedione (2,5-HD) administration. The effects of 2,5-HD on rat pyramidal tract were studied electrophysiologically and histopathologically. Male rats were given 0.5% 2,5-HD in their drinking water for 4, 6 or 8 wk. Spinal motor conduction velocity was measured by direct electrical stimulation and was examined histopathologically by electron microscopy. Rats treated with 2,5-HD had reduced spinal motor conduction velocity at 6 wk and their pyramidal tract axons had decreased cross-sectional areas at 4 wk. The mean number of neurofilaments in myelinated axons of rats treated with 2,5-HD for 8 wk was 42.1% of that found in control rats, but the number of microtubules was not significantly different. The ratio of neurofilaments to microtubules in rats treated with 2,5-HD for 4 wk was less than 1.0 in 30.9% of myelinated fibers, while in control rats it was greater than 1.0 in all axons. These changes in spinal pyramidal tract were detected relatively early after 2,5-HD administration. These results in rats indicate the need for further studies of 2,5-HD neurotoxicity in the human central nervous system.