Inflammatory mediators in diabetic and non-diabetic lumbosacral radiculoplexus neuropathy

Nobutoshi Kawamura, P. James B. Dyck, Ann M. Schmeichel, Ja Nean K. Engelstad, Phillip A. Low, Peter J. Dyck

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Nerve microvasculitis and ischemic injury appear to be the primary and important pathogenic alterations in lumbosacral radiculoplexus neuropathy of patients with (DLRPN) and without (LRPN) diabetes mellitus (DM). Here, we examine the involvement of inflammatory mediators in DLRPN and LRPN. Paraffin sections of sural nerves from 19 patients with DLRPN, 13 patients with LRPN, and 20 disease control patients were immunostained for intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and nuclear factor αB (NF-αB). The findings were correlated with histopathology. The pathologic and immunohistochemical alterations of DLRPN and LRPN nerves were indistinguishable. The nerves of both types of LRPN had a significantly greater number of ICAM-1 positive vessels than did the controls (P < 0.01). TNF-α expression was seen in Schwann cells and some macrophages of DLRPN and LRPN nerves, whereas IL-6 expression was minimal. There was greater NF-αB immunoreactivity in vessels and endoneurial cells of DLRPN and LRPN nerves than of the controls (P < 0.001). NF-αB expression correlated with the number of empty nerve strands (P < 0.01) and the frequency of axonal degeneration (P < 0.05), whereas TNF-α expression correlated inversely with the number of empty nerve strands of teased fibers (P < 0.05). Our findings suggest that up-regulation of inflammatory mediators target different cells at different disease stages and that these mediators may be sequentially involved in an immune-mediated inflammatory process that is shared by both DLRPN and LRPN. Up-regulated inflammatory mediators may be immunotherapeutic targets in these two conditions.

Original languageEnglish (US)
Pages (from-to)231-239
Number of pages9
JournalActa neuropathologica
Volume115
Issue number2
DOIs
StatePublished - Feb 1 2008

Keywords

  • Diabetic amyotrophy
  • Diabetic lumbosacral radiculoplexus neuropathy
  • Intercellular adhesion molecule-1
  • Nuclear factor kappa B
  • Peripheral neuropathy
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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