Chronic peripheral nerve compression disrupts paranodal axoglial junctions

• Published in: Muscle & nerve Vol. 55; no. 4; pp. 544 - 554
• Main Authors: Otani, Yoshinori, Yermakov, Leonid M., Dupree, Jeffrey L., Susuki, Keiichiro
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.04.2017
• Subjects: Animals; Ankyrins - metabolism; Arthrogryposis - pathology; Arthrogryposis - physiopathology; axon–glia interactions; Cell adhesion & migration; Cell Adhesion Molecules - metabolism; Cell Adhesion Molecules, Neuronal - metabolism; compression neuropathy; Disease Models, Animal; Evoked Potentials, Motor - physiology; Female; Functional Laterality; Gene Expression Regulation; Hereditary Sensory and Motor Neuropathy - pathology; Hereditary Sensory and Motor Neuropathy - physiopathology; Mice; Mice, Inbred C57BL; Microscopy, Electron, Transmission; mouse model; Nerve Growth Factors - metabolism; Neural Conduction - physiology; node of Ranvier; paranodal junction; Ranvier's Nodes - metabolism; Ranvier's Nodes - pathology; Ranvier's Nodes - ultrastructure; Sciatic Nerve - pathology; Sciatic Nerve - physiopathology; Sciatic Nerve - ultrastructure; Shab Potassium Channels - metabolism; paranodal junction; compression neuropathy; axon-glia interactions; mouse model; node of Ranvier
• ISSN: 0148-639X; 1097-4598
• DOI: 10.1002/mus.25273

ABSTRACT Introduction Peripheral nerves are often exposed to mechanical stress leading to compression neuropathies. The pathophysiology underlying nerve dysfunction by chronic compression is largely unknown. Methods We analyzed molecular organization and fine structures at and near nodes of Ranvier in a compression neuropathy model in which a silastic tube was placed around the mouse sciatic nerve. Results Immunofluorescence study showed that clusters of cell adhesion complex forming paranodal axoglial junctions were dispersed and overlapped frequently with juxtaparanodal components. These paranodal changes occurred without internodal myelin damage. The distribution and pattern of paranodal disruption suggests that these changes are the direct result of mechanical stress. Electron microscopy confirmed loss of paranodal axoglial junctions. Conclusions Our data show that chronic nerve compression disrupts paranodal junctions and axonal domains required for proper peripheral nerve function. These results provide important clues toward better understanding of the pathophysiology underlying nerve dysfunction in compression neuropathies. Muscle Nerve 55: 544–554, 2017