Reperfusion nerve injury: pathology due to reflow and prolonged ischaemia

Ischaemia plays an important role in the development of pathological changes in various neuropathies. Nerve pathology in acute ischaemic injury has been delineated longitudinally in peripheral nerve and reperfusion injury could amplify ischaemic pathology. We examined ischaemia/reperfusion-induced pathological changes along the length of sciatic, tibial and peroneal nerves from pelvic to ankle levels. Pathological features were correlated with the degree of postischaemic nerve blood flow (NBF) restoration, measured by a laser Doppler flowmeter, and the blood-nerve barrier function by a horseradish peroxidase (HRP) technique. Major arteries which supply rat hindlimb were occluded for 3, 5, or 7 hours, and reperfusion was accomplished by the removal of vascular clips. Nerve pathology was assessed after 12, 24 and 48 hours, and 5 and 7 days of reperfusion. Pathological alterations at the thigh level included vascular swelling, endoneurial and intramyelinic oedema, demyelination, thrombosis, and red blood cell (RBC) extravasation. A paucity of axonal degeneration was also characteristic at this level. By contrast, the distal nerve from knee to ankle showed evidence of extensive axonal changes, occluded vessels, and panfascicular nerve fibre and vascular degeneration. Postischaemic NBF reflow was confirmed at the thigh level immediately, 24 and 48 hours after reperfusion, whereas NBF restoration at the knee to calf level was less than preischaemic values. HRP leakage was found in both proximal and distal nerve segments. In conclusion, we demonstrated different types of structural changes along the length of ischaemic/reperfused rat sciatic nerves. The present study suggests that pathological abnormalities at the thigh level are most likely due to reoxygenation of ischaemia-inflicted endothelial cells, and distal morphological changes could be induced by prolonged ischaemia resulting from occluded vessels.