The peripheral nerve pathology in ischaemic limbs with atherosclerotic peripheral vascular diseases (PVD) is difficult to ascertain because of the limited number of reports. In addition, it has been debated whether chronic ischaemia per se could cause morphological abnormalities in peripheral nerves. In this prospective study, we examined pathological findings in the sural, saphenous, deep peroneal, superficial peroneal and tibial nerves, taken from seven acutely and nine chronically ischaemic amputated legs in which ischaemia was due to non-diabetic severe PVD. For morphological comparison, nerves were also taken from amputated legs without ischaemic disease and those in which PVD was associated with diabetes. In acutely ischaemic nerves, pathological changes were dependent upon the duration of ischaemia. Axonal degeneration of both myelinated and unmyelinated nerve fibres (MFs and UMFs) with occluded vessels was prominent, if acute ischaemia was present for > 24 h. Focal lesions, a hallmark of acute ischaemic neuropathy, were seen in both acute and chronic PVD nerves. Chronic PVD nerves also revealed considerable variations in the density of MFs between the fascicles of individual nerves and between the nerves of individual subjects: demyelination and remyelination, endoneurial oedema particularly at the subperineurial region, swollen endothelial cells, various but infrequent axonal changes, and relative preservation of UMFs were also seen. All pathological changes found in acute and chronic PVD nerves, except for a high rate demyelinated and remyelinated nerve fibres, have been described in experimental models of acute ischaemic/reperfusion injury. Demyelination could be induced by chronic ischaemia. Thus, pathological alterations in chronic ischaemic neuropathy may be due to the combined effects of acute ischaemia/reperfusion and chronic hypoxia.
We investigated the pathological appearance of acute inflammation and its role in the development of demyelination in reperfused rat sciatic, tibial, and peroneal nerves after a 5‐hour period of near‐complete ischemia. Polymorphonuclear neutrophil migration was seen early in the endoneurial lesion. After 18 hours of reperfusion, there was maximal intercellular adhesion molecule‐1 expression on endoneurial vessels, and polymorphonuclear neutrophil accumulation was then prominent, reaching a peak 24 hours after reperfusion. Endoneurial mononuclear macrophages increased nearly fourfold after 48 to 72 hours of reperfusion. Macrophages were observed invading Schwann cells and myelin lamellae with associated demyelination. Thus, this study provides evidence of macrophage‐associated demyelination after reperfusion similar to that seen in inflammatory neuropathies. Ann Neurol 2000; 47:71–79
We investigated the pathological appearance of acute inflammation and its role in the development of demyelination in reperfused rat sciatic, tibial, and peroneal nerves after a 5-hour period of near-complete ischemia. Polymorphonuclear neutrophil migration was seen early in the endoneurial lesion. After 18 hours of reperfusion, there was maximal intercellular adhesion molecule-1 expression on endoneurial vessels, and polymorphonuclear neutrophil accumulation was then prominent, reaching a peak 24 hours after reperfusion. Endoneurial mononuclear macrophages increased nearly fourfold after 48 to 72 hours of reperfusion. Macrophages were observed invading Schwann cells and myelin lamellae with associated demyelination. Thus, this study provides evidence of macrophage-associated demyelination after reperfusion similar to that seen in inflammatory neuropathies.
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