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.

High force reaching task induces widespread inflammation, increased spinal cord neurochemicals and neuropathic pain

“…In Sommerich’s study, the significant decline in NCV (25–31%) induced by their repetitive task recovered to normal levels after cessation of the task. In contrast, Gupta and colleagues found no recovery after a 65% reduction in NCV even after 12 months of rest (Gupta et al, 2003). We have not yet examined the effects of rest in our model.…”

Transplantation of Preconditioned Schwann Cells Following Hemisection Spinal Cord Injury

“…19 Previous studies have demonstrated a massive proliferation of Schwann cells in peripheral nerve segments subjected to sustained mechanical stimulation. [22][23][24][25] This proliferative response is accompanied by sprouting of undamaged axons, suggesting that Schwann cells are activated in a way that promotes axonal growth. To date, there has been limited study focusing on the role of these mechanically stressed Schwann cells in a spinal cord injury model by creating a permissive, pro-regenerative behavior.…”

“…Sprague-Dawley rats (n ϭ 30) served as donors for preconditioned and control sciatic nerve grafts as described previously. 23 Briefly, sciatic nerves were exposed using the gluteal splitting approach. The control nerve segments were simply exposed, while with the experimental group, the sciatic nerves were compressed with inert, nonconstrictive tubing with inner diameter 1.3 mm, to create chronic nerve compression.…”

Nitric oxide in cerebrospinal fluid and local inducible nitric oxide synthase after cauda equina compression in rats

“…We also reported that preoperative CSF NO x levels are useful as a quantitative predictor for postoperative pain relief in LCS [12]. Although little is known about the origin of NO x in LCS, iNOS protein and its encoding mRNA have been detected at the constriction site in some studies using peripheral nerve compression models [13][14][15]. These findings suggest that elevated CSF NO x levels in LCS patients are derived from iNOS that is induced at the compressed cauda equina or nerve roots.…”