PERIVASCULAR DEMYELINATION AND INTRAMYELINIC EDEMA IN REPERFUSION NERVE INJURY

Nerve ischaemia plays a major role in the development of pathological alterations in various neuropathies, and the effects of ischaemia are amplified by reperfusion in various tissues. While pathological altera tions in acutely ischaemic nerve have be:en established, nerve patholo gy resulting from reperfusion injury has never been elucidated. To eva luate what cell type in peripheral nerve is affected by reoxygenation following a hypoxic episode, we developed an animal model of transient severe limb ischaemia. Near-complete ischaemia, confirmed by the meas urement of nerve blood flow, was achieved by clamping multiple arterie s of supply to rat hindlimb. After 3, 5 or 7 h of limb ischaemia, vasc ular clips were released to reperfuse blood flow. Pathology in sciatic , tibial and peroneal nerves at the lower thigh level was examined at 7 d after reperfusion. All reperfused nerves developed demyelinated ne rve fibres, particularly in perivascular regions. Although 3 h of isch aemia followed by reperfusion caused demyelination, perivascular demye lination was more prominent after a longer period of ischaemia with re perfusion. Two types of nerve oedema were observed; endoneurial oedema especially in perivascular and subperineurial spaces, and intramyelin ic oedema. Nerve fibres with intramyelinic oedema were not confined to the perivascular region. Swollen endothelial cells in endoneurial ves sels were also invariably observed. Nerve ischaemia per se, without re perfusion, did not induce these pathological changes. Because myelin a ppears to be particularly susceptible to activated free radicals, oxid ative stress, activated neutrophils, and cytokine formation seem to be important underlying mechanisms in the development of perivascular de myelination and intramyelinic oedema in ischaemic/reperfused nerves. T his study demonstrated that reperfusion causes selective damage to the myelin sheath, and reperfusion nerve injury needs therefore to be inc luded in the differential diagnosis of peripheral nerve demyelination.