Rapid repair of severed mammalian axons via polyethylene glycol-mediated cell fusion

Abstract

The ability to repair damaged mammalian axons to re-establish functional connections continues to be a goal for neuroscientists. Following axonal severance, proximal segments of mammalian axons seal themselves rapidly at the lesion site. Distal segments of severed mammalian axons undergo Wallerian degeneration within 24-72 hours. Prior to the onset of degeneration, distal axonal segments remain electrically excitable. The work described in this dissertation demonstrates that polyethylene glycol (PEG), a hydrophilic polymer, can rapidly repair severed axons by fusing the plasmalemmas of two closely apposed distal and proximal axonal segments. This plasmalemmal fusion restores morphological integrity of severed axons and their ability to conduct action potentials across the injury site. The ability to fuse proximal and distal severed axonal segments using PEG is improved when the axonal segments are exposed to antioxidants, such as melatonin and methylene blue, and also when microsutures provide additional support in transected sciatic nerves. The restoration of axonal continuity by PEG-fusion restores function, improving behavioral recovery in rats with crush-injured sciatic nerves, as well as those in which the sciatic is complete transected.