Perivascular demyelination and intramyelinic oedema 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 alterations in acutely ischaemic nerve have been established, nerve pathology resulting from reperfusion injury has never been elucidated. To evaluate 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 measurement of nerve blood flow, was achieved by clamping multiple arteries of supply to rat hindlimb. After 3, 5 or 7 h of limb ischaemia, vascular 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 nerve fibres, particularly in perivascular regions. Although 3 h of ischaemia followed by reperfusion caused demyelination, perivascular demyelination was more prominent after a longer period of ischaemia with reperfusion. Two types of nerve oedema were observed; endoneurial oedema especially in perivascular and subperineurial spaces, and intramyelinic oedema. Nerve fibres with intramyelinic oedema were not confined to the perivascular region. Swollen endothelial cells in endoneurial vessels were also invariably observed. Nerve ischaemia per se, without reperfusion, did not induce these pathological changes. Because myelin appears to be particularly susceptible to activated free radicals, oxidative stress, activated neutrophils, and cytokine formation seem to be important underlying mechanisms in the development of perivascular demyelination and intramyelinic oedema in ischaemic/reperfused nerves.(ABSTRACT TRUNCATED AT 250 WORDS)