Impaired myelinated fiber regeneration following freeze-injury in rats with streptozotocin-induced diabetes: Involvement of the polyol pathway

This study examined the effects of streptozotocin-induced diabetes mellitus and aldose reductase inhibitor (ZD5522) treatment on myelinated fiber regeneration in rats. After 2 months of diabetes, with or without ZD5522 treatment (10 mg . kg(-1). day(-1)) from induction, sciatic nerve degeneration was initiated by a punctate lesion using a liquid N-2 cooled probe. Regeneration was studied over a subsequent 14-day period using in vitro electrophysiological techniques. There was a 21.4% (P < 0.001) deficit in the maximum fiber regeneration distance in diabetic rats, 14 days postlesion. This was partially (64.9%, P < 0.01) prevented by aldose reductase inhibitor treatment, the resultant regeneration distance being not significantly different from that of age-matched nondiabetic control rats. The regeneration rate, assessed from data collected 4, 9 and 14 days postlesion, was 23.7% (P < 0.001) reduced by diabetes and ZD5522 treatment provided 73.1% protection (P < 0.01). We conclude that polyol pathway activity is involved in impaired regeneration in experimental diabetes, potential pathophysiological mechanisms involving a reduction in neurotrophic support and impaired endoneurial blood supply.