Effects of nerve compression on fast axonal transport in streptozotocin-induced diabetes mellitus

Abstract

Summary. The hypothesis that nerves in diabetes mellitus exhibit an increased susceptibility to compression was experimentally tested. Inhibition of fast axonal transport was induced by local compression in sciatic nerves of rats with streptozotocin-induced diabetes mellitus. Fast anterograde axonal transport was measured after application of 3H-leucine to the motor neurone cell bodies in the spinal cord. The sciatic nerve was subjected to local, graded compression in vivo by a small compression chamber. The amount of accumulation of proteins was quantified by calculation of a transport block ratio. Compression at 30 mm Hg for 3 h induced a significantly greater (p<0.05) accumulation of axonally transported proteins at the site of compression in nerves of diabetic animals (transport block ratio: 1.01_+0.35; n=7) than in nerves of controls (0.67 + 0.16; n = 7). Accumulation was significantly higher in ligature experiments of both control (1.34_+ 0.44; n = 8; p < 0.01) and diabetic animals (1.45 _+ 0.30; n = 8; p < 0.05), indicating that the block of transport in compressed nerves was incomplete. Neither sham compressed diabetic (0.50+0.09; n=6) nor control (0.49_+0.11; n=6) nerves showed any block of axonal transport. The possible causes of the increased inhibition of fast axonal transport in diabetic rats are discussed. The results indicate that diabetes may lead to an increased susceptibility of peripheral nerves to compression.Key words: Compression, diabetes mellitus, streptozotocin, axonal transport, compression syndromes, mononeuropathy, neuropathy.The clinical symptoms of neuropathy in diabetes mellitus are well known, and include primarily sensory complaints, occasionally accompanied by muscular weakness and autonomic symptoms. Sensory and muscular dysfunction in extremities may, however, also be caused by entrapment of peripheral nerves such as ulnar nerve compression at the elbow and median nerve compression at the wrist, i. e. the carpal tunnel syndrome. A high frequency of such mononeuropathies has been reported among diabetic patients, which suggests enhanced vulnerability of peripheral nerves to trauma [1]. It has also been suggested that peripheral nerves in experimental diabetes have a greater susceptibility to injury [2][3][4].Axonopathy, which can be characterised by abnormalities in axonal transport, may be an important factor in the neuropathies which accompany diabetes [5][6][7]. Based upon previous experience on the effects of peripheral nerve compression [for review see 8] and the hypothesis that diseased neurones, such as those in diabetes mellitus, are more susceptible to compression * Present address: Department of Anatomy and Neurobiology, Washington University, School of Medicine, St. Louis, Missouri, USA trauma than are healthy neurones [9], we decided to investigate the effects of experimental nerve compression on fast axonal transport in streptozotocin-induced diabetes mellitus Materials and methods Animals and induction of diabetesRandom-bred and weight-matched female Sprague-Dawle...

Pressure-induced inhibition of fast axonal transport of proteins in the rabbit vagus nerve in galactose neuropathy: prevention by an aldose reductase inhibitor

“…The altered susceptibility of the fast transport process to local mild pressure is consistent with previous work in the streptozotocin-diabetic rat [1,2]; the results confirm that the effect can be observed in small nonmyelinated sensory nerve fibres of the vagus nerve. However, in rat and rabbit sciatic nerve there is conflicting evidence for and against an increased nerve water content [5,6,25,26].…”

“…Streptozotocin-induced experimental diabetes in the rat leads to an increase in the inhibition of the fast axonal transport of proteins in the sciatic nerve by local compression [1]. This phenomenon is related to the intraneural accumulation in diabetes of the sugar alcohol sorbitol, since the increased inhibition of transport is prevented by administration of the aldose reductase inhibitor 'Statil' (ICI 128436) [2].…”

Focal and multifocal neuropathies

“…Thus, an increased susceptibility to malfunction of the nerve may occur after compression if there is an underlying alteration in both slow [1] and fast [2] axonal transport. The presence of endoneurial edema may lead to increased capillary oxygen diffusion distances as well as an increase in the external pressure directed on axons.…”

Biologic Basis of Nerve Decompression Surgery for Focal Entrapments in Diabetic Peripheral Neuropathy

“…Dahlin et al 39 demonstrated on a molecular level that in streptozotocin-induced diabetic rats localized compression of the sciatic nerve leads to significant reduction in fast axonal transport. Using a graded compression, it was noted that at pressures of 20-30 mmHg, axonal transport was blocked.…”