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We have used uptake or exclusion of extracellular fluorescent dye to measure the ability of rat hippocampal B104 cells or rat sciatic nerves to repair (seal) transected neurites in vitro or transected axons ex vivo. We report that endogenous sealing in both preparations is enhanced by Ca<jats:sup>2+<\/jats:sup>\u2010containing solutions and is decreased by Ca<jats:sup>2+<\/jats:sup>\u2010free solutions containing antioxidants such as dithiothreitol (DTT), melatonin (MEL), methylene blue (MB), and various toxins that decrease vesicular interactions. In contrast, the fusogen polyethylene glycol (PEG) at 10\u201350 mM artificially seals the cut ends of B104 cells and rat sciatic axons within seconds and is not affected by Ca<jats:sup>2+<\/jats:sup> or any of the substances that affect endogenous sealing. At higher concentrations, PEG decreases sealing of transected axons and disrupts the plasmalemma of intact cells. These PEG\u2010sealing data are consistent with the hypothesis that lower concentrations of PEG directly seal a damaged plasmalemma. We have considered these and other data to devise a protocol using a well\u2010specified series of solutions that vary in tonicity, Ca<jats:sup>2+<\/jats:sup>, MB, and PEG content. These protocols rapidly and consistently repair (PEG\u2010fuse) rat sciatic axons in completely cut sciatic nerves in vivo rapidly and dramatically to restore long\u2010lasting morphological continuity, action potential conduction, and behavioral functions. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jnr.23022","type":"journal-article","created":{"date-parts":[[2012,2,3]],"date-time":"2012-02-03T09:02:50Z","timestamp":1328259770000},"page":"955-966","source":"Crossref","is-referenced-by-count":49,"title":["Cellular mechanisms of plasmalemmal sealing and axonal repair by polyethylene glycol and methylene 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