Forced retraction of spinal root injury enhances activation of p38 MAPK cascade in infiltrating macrophages

• Published in: Neuropathology 2005-03, Vol.25 (1), p.37-47
• Main Authors: Nomura, Hiroshi, Furuta, Akiko, Tanaka, Yoshitaka, Iwaki, Toru
• Format: Article
• Language: English
• Subjects: Animals; Antigens, CD - metabolism; Brachial Plexus - injuries; Disease Models, Animal; Female; Immunohistochemistry; LGP107/96; Lysosomal Membrane Proteins; Macrophage Activation; Macrophages - metabolism; Microscopy, Confocal; MKK3; p38 MAPK; p38 Mitogen-Activated Protein Kinases - metabolism; Rats; Rats, Wistar; Rhizotomy; root-rupture injury; Rupture; Sialoglycoproteins - metabolism; Spinal Cord - metabolism; Spinal Cord - pathology; Spinal Nerve Roots - injuries; Spinal Nerve Roots - metabolism; Spinal Nerve Roots - pathology; Tumor Necrosis Factor-alpha
• ISSN: 0919-6544; 1440-1789
• DOI: 10.1111/j.1440-1789.2004.00584.x

Root‐rupture injury is a type of preganglionic brachial plexus injury resulting from traction force, where a small section of the spinal root is usually left behind. We have established experimental models of both root‐rupture injury with traction force and rhizotomy without traction force in rats and we examined the activation of microglia/macrophages in both conditions. LGP107 and LGP96, which are rat homologs of lysosome‐associated membrane proteins, were most useful as immunohistochemical markers of mononuclear phagocytes. The metabolic activation of macrophages was analyzed by immunohistochemistry with a series of antibodies against tumor necrosis factor‐alpha (TNF‐alpha), cathepsin B, p38 mitogen‐activated protein kinase (MAPK), and mitogen‐activated kinase kinase 3 (MKK3). Both root‐rupture injury and rhizotomy rapidly induced the aggregation of numerous macrophages from the injured dorsal root to the dorsal funiculus and TNF‐alpha was highly expressed by the macrophages in the injured dorsal root at 48 h. Activation of p38 MAPK was preferentially observed in the macrophages at the ruptured dorsal root; however, only slight activation of p38 MAPK was observed at the rhizotomized dorsal root. These findings suggest that traction injury of the spinal root might induce activation of the p38 MAPK cascade and production of TNF‐alpha in the infiltrating macrophages, both of which might participate in aggravation of the root injury.