Treatment with an aldose reductase inhibitor can reduce the susceptibility of fast axonal transport following nerve compression in the streptozotocin-diabetic rat

Abstract

The effect of treatment with an aldose reductase inhibitor on the susceptibility of peripheral nerves to compression was studied in rats made diabetic by the injection of streptozotocin (50 mg·kg-1). The response to nerve compression was determined in untreated diabetic rats after 22 days of diabetes and compared with the response in two similar groups of diabetic rats which had been treated with the aldose reductase inhibitor 'Statil' (ICI 128436; 25 mg·kg-1· day-1 orally) either from the induction of diabetes or for 7 days prior to nerve compression. Two groups of non-diabetic rats were treated with 'Statil' for either 22 days or 7 days to act as controls. Inhibition of fast axonally transported proteins was induced by local compression of the sciatic nerves 4 h after application of 3H-leucine to the motor neurone cell bodies in the spinal cord. The inhibition of fast axonal transport was quantified by calculation of a transport block ratio. Compression at 30 mmHg for 3 h induced a significantly greater (p<0.05) inhibition of axonal transport at the site of compression in nerves of untreated diabetic rats (transport block ratio 0.96±0.24, n=8) than in nerves of control rats treated with the aldose reductase inhibitor for either the shorter time of 7 days (0.71±0.17, n=10) or the longer time of 22 days (0.69±0.08, n=5). In diabetic rats treated with the aldose reductase inhibitor for 22 days the inhibition (0.77±0.12, n=6) was significantly less than that in untreated diabetic rats; treatment for 7 days reduced the transport block ratio to 0.85±0.11 (n=8), but the effect was not significant. Treatment for 22 days prevented the marked increase in nerve sorbitol found in the diabetic rats but did not prevent a fall in nerve myo-inositol. The results indicate that treatment with an aldose reductase inhibitor for a sufficient period of time can reduce the increased susceptibility of peripheral nerves to compression in streptozotocin-induced diabetes mellitus in the rat by a mechanism which may be related to the prevention of increases in sorbitol in the nerves. © 1987 Springer-Verlag.