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 N2 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.
Love
A
A
Department of Biomedical Sciences, University of Aberdeen, Scotlan, UK.
Cotter
M A
MA
Cameron
N E
NE
D000083:Acetanilides / Q000494:pharmacology; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000704:Analysis of Variance; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005615:Freezing; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000502:physiology*; D013012:Sorbitol / Q000378:metabolism*; D013450:Sulfones / Q000494:pharmacology
D000083:Acetanilides; D004791:Enzyme Inhibitors; D013450:Sulfones; C090184:ZENECA ZD 5522; D013012:Sorbitol; D000449:Aldehyde Reductase