Peripheral demyelination and remyelination initiated by the @entity460 -selective ionophore XXXX : in vivo observations.

@entity17 @entity6579 @entity35 @entity39 @entity19 @entity1360 @entity460 @entity3365 @entity141 @entity528
Incubation of nerve with @entity141 and the divalent cation ionophores @entity3365 or @entity1360 , causes a prompt vesiculation of the myelin at the paranodes and Schmidt-Lanterman incisures. The vesiculation appears to be dependent upon a rise in the intracellular @entity460 concentration of the affected Schwann cells. To determine whether a similar vesiculation might occur in vivo, and to examine the long term consequences of ionophore exposure, the sciatic nerves of @entity35 and @entity19 were injected with @entity1360 and examined histologically after intervals of 1 h to 75 days. A prompt myelin vesiculation was again observed, and this spread from the paranodes and incisures to invade regions of formerly compact myelin: segmentally demyelinated axons were common 7 days post-injection. The lesions were large, and involved up to 95% of the fibres in the @entity19 . There was little evidence of either @entity39 , or @entity528 in either species. The appearance and spatio-temporal progression of the lesion was strikingly similar to that seen after the intraneural injection of @entity6579 or phospholipase A2. However, in the ionophore lesion, not all the @entity17 was effected by myelin vesiculation, for up to 30% of the affected fibres showed evidence of macrophage-mediated stripping. Macrophage stripping was confined to internodes already affected by vesiculation. Most of the myelin debris was removed by macrophages, and myelin debris was only rarely observed within Schwann cells. Remyelination was initiated in nearly all the affected fibres by 21 days, and by 2 months all affected fibres were invested with thin, new myelin sheaths. These findings may be relevant to immune-mediated @entity17 .
