Degeneration, Trophic Interactions, and Repair of Severed Axons: A Reconsideration of Some Common Assumptions

Abstract

We suggest that several interrelated properties of severed axons (degeneration, trophic dependencies, initial repair, and eventual repair) differ in important ways from commonly held assumptions about those properties. Specifically, (1) axotomy does not necessarily produce rapid degeneration of distal axonal segments because (2) the trophic maintenance of nerve axons does not necessarily depend entirely on proteins transported from the perikaryon—but instead axonal proteins can be trophically maintained by slowing their degradation and/or by acquiring new proteins via axonal synthesis or transfer from adjacent cells (e.g., glia). (3) The initial repair of severed distal or proximal segments occurs by barriers (seals) formed amid accumulations of vesicles and/or myelin delaminations induced by calcium influx at cut axonal ends—rather than by collapse and fusion of cut axolemmal leaflets. (4) The eventual repair of severed mammalian CNS axons does not necessarily have to occur by neuritic outgrowths, which slowly extend from cut proximal ends to possibly reestablish lost functions weeks to years after axotomy—but instead complete repair can be induced within minutes by polyethylene glycol to rejoin (fuse) the cut ends of surviving proximal and distal stumps. Strategies to repair CNS lesions based on fusion techniques combined with rehabilitative training and induced axonal outgrowth may soon provide therapies that can at least partially restore lost CNS functions.