Protective effects of progesterone on sciatic nerve function and structure in experimental diabetic neuropathy

Diabetic neuropathy is one of the most common complications affecting more than 50-60% of diabetic patients and it is a common cause of non-traumatic amputation and autonomic failure. Neuroactive steroids, such as progesterone (PROG), have been recently identified as promising neuroprotective agents in several models of neurodegeneration. In this study, we investigated the potential neuroprotective effects of PROG in an experimental model of diabetic neuropathy. Thirty male rats were randomly divided into 3 groups (with 10 rats in each), control (non-diabetic), untreated diabetic and diabetic PROG-treated. Diabetes was induced in the animals by a single dose injection of streptozotocin (STZ, 55 mg kg-1, i.p.). In the PROG-treated group, 4 weeks after inducing of diabetes; the animals were treated with PROG (8 mg kg-1, i.p., every two days) for 6 weeks Diabetic rats showed a significant reduction in motor nerve conduction velocity (MNCV), mean myelinated fibers (MFs) diameter, axon diameter and myelin sheath thickness in the sciatic nerve after 6 weeks. In the untreated diabetic group, endoneurial edema was observed in sciatic nerve and the numbers of MFs with enfolding into the axoplasm, irregularity of fibers, myelin sheath with unclear boundaries and alteration in myelin compaction were also increased. Long-term treatment with PROG increased MNCV significantly and prevented all these abnormalities in treated diabetic rats. Our findings indicated that PROG as a therapeutic approach can protect neurophysiologic and histomorphologic alterations induced by peripheral diabetic neuropathy.