title: Macrophage recruitment follows the pattern of inducible nitric oxide synthase expression in a model for carpal tunnel syndrome.
abstract: Chronic nerve compression (CNC) induces a permeability change in neural vasculature. As recent evidence has shown that an alteration in reactive oxidative species (ROS) is related to neural degradation and regeneration, we evaluated whether inducible nitric oxide synthase (iNOS) plays a role in a rat model for CNC. Semi-quantitative analysis of iNOS mRNA and protein were performed with in situ hybridization and immunohistochemistry, respectively, at 3, 5, and 9 months post-operatively. At 3 months, iNOS mRNA was up-regulated in the perineurium of the proximal nerve with detectable changes in compressed and distal nerve segments. This expression continued to increase in the perineurium of 5-month proximal and compressed nerve segments with distal nerve demonstrating only a slight up-regulation of iNOS mRNA. At 9 months, iNOS mRNA expression was observed in both compressed and distal nerve. iNOS protein expression followed the same pattern of iNOS mRNA. As the perineurium is the blood-nerve barrier, the data suggests that these changes maybe mediated at the level of the perineurium. As macrophages release iNOS, we also evaluated whether macrophage recruitment followed the same pattern as iNOS expression. The results of ED-1 immunostaining for macrophages indicate that macrophages were localized to the outer one-third of cross sections during early time points. At later time points, macrophages were distributed diffusely throughout the nerve sections. Contrary to Wallerian degeneration, which elicits a relatively immediate signal for macrophage recruitment, CNC provides a slow, sustained stimulus for macrophage recruitment, which may be responsible for the up-regulation of iNOS gene expression.
authors.affiliation: Peripheral Nerve Research Lab, Department of Orthopaedic Surgery, University of California, Irvine, Med Sci I Room B120, Irvine, California 92697, USA. ranjang@uci.edu
authors.forename: Ranjan
authors.initials: R
authors.lastname: Gupta
authors.forename: Yi-Mei
authors.initials: YM
authors.lastname: Lin
authors.forename: Phong
authors.initials: P
authors.lastname: Bui
authors.forename: Tom
authors.initials: T
authors.lastname: Chao
authors.forename: Charles
authors.initials: C
authors.lastname: Preston
authors.forename: Tahseen
authors.initials: T
authors.lastname: Mozaffar
mesh_terms: D000818:Animals; D002349:Carpal Tunnel Syndrome / Q000201:enzymology* / Q000473:pathology; D002465:Cell Movement / Q000502:physiology*; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D008264:Macrophages / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat