Ej. Lehning et al., AXONAL ATROPHY IS A SPECIFIC COMPONENT OF 2,5-HEXANEDIONE PERIPHERAL NEUROPATHY, Toxicology and applied pharmacology, 135(1), 1995, pp. 58-66
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.