Chronic nerve compression induces local demyelination and remyelination in a rat model of carpal tunnel syndrome.
In a previous study, we demonstrated that chronic compression of rat sciatic nerve, a model of compressive neuropathies, triggered dramatic Schwann cell proliferation and concurrent apoptosis. Importantly, this Schwann cell response occurred before there are signs of overt axonal pathology, raising the question of whether there are alterations in axonal myelination in the areas of the nerve in which Schwann cell apoptosis and proliferation occur. Here, we use nerve teasing techniques and unbiased stereology to assess myelination in nerves after 1 and 8 months of compression. Evaluations of myelin thickness and axonal diameter (AD) using design-based, unbiased stereology revealed alterations in myelin structure that indicate remyelination, specifically a dramatic decrease in the average internodal length (IL) and an increase in the proportion of axons with thin myelin sheaths. The mean IL was reduced after 1 month of chronic nerve injury with no further decrease in IL at 8 months. There was limited change in average axonal diameter at both 1 and 8 months. Measures of myelin thickness revealed not only a greater than 6-fold increase in the number of axons with very thin (<5 microm thickness) myelin sheaths, but also a proportional decrease in the number of axons with the thick myelin sheaths characteristic of normal nerve. These results confirm that an early consequence of chronic nerve compression (CNC) is local demyelination and remyelination, which may be the primary cause of alterations in nerve function during the early period post-compression.
Gupta
Ranjan
R
Department of Orthopaedic Surgery, College of Medicine, University of California, Irvine, CA 92657, USA. ranjang@uci.edu
Rowshan
Kasra
K
Chao
Tom
T
Mozaffar
Tahseen
T
Steward
Oswald
O
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D002349:Carpal Tunnel Syndrome / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D002908:Chronic Disease; D003711:Demyelinating Diseases / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D008297:Male; D009186:Myelin Sheath / Q000378:metabolism* / Q000648:ultrastructure; D009408:Nerve Compression Syndromes / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D009431:Neural Conduction / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000378:metabolism / Q000473:pathology