Sciatic nerve of diabetic rat treated with epoetin delta: effects on C-fibers and blood vessels including pericytes.
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 beta receptor subunit of the interleukin 3 receptor (IL-3Rbeta) 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 CGRP-positive 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-3Rbeta was in pericytes. Some perivascular autonomic nerves were damaged and IL-3Rbeta 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.
Loesch
Andrzej
A
Research Department of Inflammation, University College London Medical School, Royal Free Campus, London, UK. aloesch@ntlworld.com
Tang
Helen
H
Cotter
Mary A
MA
Cameron
Norman E
NE
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D053648:Cytokine Receptor Common beta Subunit / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000503:physiopathology*; D004921:Erythropoietin / Q000494:pharmacology* / Q000627:therapeutic use; D007150:Immunohistochemistry; D008297:Male; D055806:Microvessels / Q000187:drug effects / Q000473:pathology*; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D020286:Pericytes / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D012039:Regional Blood Flow / Q000187:drug effects; D012584:Sciatic Nerve / Q000166:cytology / Q000187:drug effects* / Q000473:pathology*
D053648:Cytokine Receptor Common beta Subunit; D011994:Recombinant Proteins; D004921:Erythropoietin; C516023:epoetin delta; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D015740:Calcitonin Gene-Related Peptide