Paranodal structural abnormalities in rat CNS myelin developing in vivo in the presence of implanted O1 hybridoma cells.

O1 hybridoma cells, which produce a monoclonal IgM antigalactocerebroside, were implanted into the spinal cords of immature and mature rats and the cords examined 5-24 days later. Study of the younger group, in which myelin was developing at the time of implantation, revealed examples of abnormal myelin sheaths in which the repeat period was markedly increased. The paranodal regions of these abnormal sheaths were superficially normal in configuration; i.e. myelin lamellae terminated one by one as 'terminal loops' that indented the axolemma and formed normal axoglial junctions displaying periodic 'transverse bands'. Neighbouring terminal loops are normally joined by tight junctions that block passage of tracers from the paranodal periaxonal space into the compact myelin, as seen after implantation of a control hybridoma. In the abnormal sheaths that developed after O1 implantation, in contrast, terminal loops were usually widely separated from each other. As a result, multiple pathways from the paranodal periaxonal space into the myelin sheath remained patent, forming potential routes for shunting nodal action currents. This subtle abnormality could thus compromise conduction, even though the sheaths might appear to be normally myelinated at the histological level. Equivalent abnormalities in human neurological diseases, including multiple sclerosis and paraproteinemic neuropathies, could underlie functional loss in the absence of frank demyelination.