AXONAL ATROPHY IS A SPECIFIC COMPONENT OF 2,5-HEXANEDIONE PERIPHERAL NEUROPATHY

To assess the relevance of previously identified axonal atrophy to hex anedione neuropathy, the present study quantitated fiber size in perip heral nerve of rats intoxicated with 2,5-hexanedione (HD) by either or al ingestion (0.4% in drinking water) or ip injection (0.4 g/kg/day). Prior to the appearance of neurobehavioral deficits, rats exposed to o ral HD (77 days) exhibited axonal atrophy in proximal sciatic nerve an d giant axonal swellings in distal tibial nerve, As oral-treated rats progressed to moderate (86 days) and severe (103 days) hindlimb weakne ss, both nerve regions contained a mixed population of atrophied and s wollen axons, Rats injected with HD ip were sampled at behavioral endp oints that matched those of oral HD-treated rats. In sciatic and tibia l nerves from rats treated ip, reductions in the axon area were simila r to oral exposure, However, ip treatment did not produce giant axonal swellings in either nerve, Thus, although both routes of administrati on caused equivalent behavioral neurotoxicity, the expression of axona l swellings was route-dependent. This suggests that the production of swellings depends upon the HD exposure pattern, In contrast, axonal at rophy was prevalent in both nerve regions sampled and developed in par allel with behavioral deficits, In addition, atrophy was expressed reg ardless of the intoxication route which indicates that atrophy can occ ur independent of axonal swellings, Together, these attributes suggest that atrophy is a specific component of HD neurotoxicity. (C) 1995 Ac ademic Press, Inc.