The effects of 2,5-hexanedione on axonal regeneration after nerve crush in the rat

The pattern of recovery of myelinated axons in the posterior tibial nerve after crushing was studied in rats chronically intoxicated with 2,5-hexanedione. It was given for 2 weeks before crushing (200 mg/kg i.p. 5 times a week) or additionally for two further weeks after the nerve crush. Two animals were examined from each group at approximately 1,2,3,4 and 8 weeks later. Return of function in poisoned animals was slower than in the controls. The numbers of regenerating myelinated fibres was severely reduced in poisoned animals up to 4 weeks later, but by 8 weeks the numbers equalled those in the control nerves. Marked impairment of initiation of neurite outgrowth was found, but once begun, axonal growth was comparable to controls and myelination occurred normally. Above the crush for 10 mm, filament-filled axonal swellings were found in poisoned animals accompanied by varying amounts of retrograde axonal degeneration. These findings are discussed in relation to the role of normal neurofilaments in axonal growth and the effects of probably cross-linking of these by 2,5-hexanedione on regenerating neurites.