Sciatic Nerve of Diabetic Rat Treated With Epoetin Delta: Effects on C-Fibers and Blood Vessels Including Pericytes

Abstract

In diabetes mellitus (DM) reduced motor and sensory properties of peripheral nerves are linked with the dysfunction of neural vasculature. We investigated C-fibers and microvessels of sciatic nerve of normal, DM, and DM + epoetin delta-treated rats. C-fibers immunoreactive for calcitonin gene-related peptide (CGRP), tyrosine hydroxylase (TH), epoetin receptor (EpoR), and common β receptor subunit of the interleukin 3 receptor (IL-3Rβ) were present in all rats, whereas in DM and epoetin-treated rats C-fibers also showed neuronal (nNOS) and inducible (iNOS) nitric oxide synthases. The cross-sectional area of CGRPpositive C-fibers was decreased in DM, but it recovered after epoetin treatment. In all conditions, vascular endothelium showed scarce immunolabeling for endothelial nitric oxide synthase (eNOS); the profound immunoreactivity for eNOS, EpoR, and IL-3Rβ was in pericytes. Some perivascular autonomic nerves were damaged and IL-3Rβ positive. Findings are discussed in terms of declined sensory conduction velocity in DM, its improvement after epoetin treatment, and the possible vascular contribution to these phenomena.