Studies on the pathogenesis and treatment of diabetic neuropahy ; mechanisms of impaired regeneration of peripheral nerve and tiral for its inhibition

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Impaired regeneration of peripheral nerve was exmained in the severed peripheral nerve of streptozotocin (STZ)-induced diabetic rats with light and electron microscopic morphometrical analysis. Immunocytochemical evaluation on the expression of nerve growth factor receptor (NFGR) was also conducted. For the further elucidation of mechanisms of impaired regeneration, Northern blot analysis on mRNA levels of neurofilament (NF-68) was also performed. In addition to these experimental studies, preliminary examinations on the human biopsied sural nerve samples to determine the NGFR expression were also undertaken.Diabetic rats showed significant reduction of mean size of regenerated nerve fibers and axon/fiber size ratio, but there was no significant difference in the number, density of regenerated myelinated nerve fibers between diabetic and normal control rats during 2-4weeks experiments after nerve section. NGFR expression was reduced in diabetic rats only at the point of 4 weeks after the section of the nerve. NF-68 mRNA expression was significantly reduced in diabetic rats as compared with normal control rats. The impaired regeneration was represented by the thin myelinated fibers which are probably related to the reduced synthesis of axonal neurofilaments. NGFR expression appeared to correlate to this abnormality. Human diabetic nerves showed high expression of NGFR similar to other axonal type of neuropathy. Thus the NGFR-NF synthesis seems to be the crucial step for the perturbation of nerve regeneration in diabetes.