Ischemia and failed regeneration in chronic experimental neuromas.
Neuromas are generally considered to be swollen uniform collections of uncontrolled aberrantly sprouting axons. In early experimental neuromas, there are substantial rises in local blood flow associated with their formation, but human studies of chronic lesions have suggested that neuromas develop ischemia and become impediments to regeneration. The issue is important because traumatically severed human nerves are frequently considered for repair some time after injury, when neuroma formation has occurred. In this work, we examined local perfusion, axon penetration and other characteristics of long-term (6 month) experimental neuromas created by sciatic nerve transection and resection of the distal sciatic nerve and its branches. The scenario was designed to model prior transection in a human nerve, where late surgical reconnection might be contemplated. Local blood flow in the extrinsic plexus of neuromas, examined using a laser Doppler flowmetry probe, declined in distal portions of the stump to values considerably lower than observed in intact nerves. Intrinsic blood flow near the stump tip, examined using microelectrode hydrogen clearance polarography was highly nonuniform and included zones with very low perfusion. Correlated with these findings were nonuniform histological features with zones of absent axons and blood vessels, progressive distal disorganization, marked declines in distal axon penetration, nonremodelled microfascicles and persistent expression of 'regenerative' axon and Schwann cell markers. Uncontrolled axon sprouting was not a feature. Longstanding neuromas include zones of relative ischemia and limited axon penetration that develop in the absence of nerve trunk reconnection. These features would limit their suitability for later repair.
Department of Clinical Neurosciences and the Neuroscience Research Group, University of Calgary, Room 182A, 3330 Hospital Drive, N.W. Calgary, Alberta T2N 4N1, Canada.
Qing-Gui
QG
Xu
Douglas W
DW
Zochodne
D000818:Animals; D007150:Immunohistochemistry; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D009416:Nerve Regeneration; D009463:Neuroma / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D010524:Peripheral Nervous System Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D012584:Sciatic Nerve