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The Journal of Neuroscience, April 1, 1999, 19(7):2442-2454

Rapid Induction of Functional and Morphological Continuity between Severed Ends of Mammalian or Earthworm Myelinated Axons

April B. Lore¹, Jeffery A. Hubbell⁴, David S. Bobb Jr¹, Martis L. Ballinger¹, Keisha L. Loftin¹, Jeffory W. Smith¹, Mark E. Smyers¹, Habacuc D. Garcia¹, and George D. Bittner^{1, 2, 3, 5}

¹ Department of Zoology, ² Institute for Neuroscience, and ³ College of Pharmacy, University of Texas at Austin, Austin, Texas 78712, ⁴ Institute for Biomedical Engineering and Department of Materials, Swiss Federal Institute of Technology and University of Zurich, CH-8044 Zurich, Switzerland, and ⁵ Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston, TX 77555-0641

The inability to rapidly restore the loss of function that results from severance (cutting or crushing) of PNS and CNS axons is a severe clinical problem. As a novel strategy to help alleviate this problem, we have developed in vitro procedures using Ca²⁺-free solutions of polyethylene glycol (PEG solutions), which within minutes induce functional and morphological continuity (PEG-induced fusion) between the cut or crushed ends of myelinated sciatic or spinal axons in rats. Using a PEG-based hydrogel that binds to connective tissue to provide mechanical strength at the lesion site and is nontoxic to nerve tissues in earthworms and mammals, we have also developed in vivo procedures that permanently maintain earthworm myelinated medial giant axons whose functional and morphological integrity has been restored by PEG-induced fusion after axonal severance. In all these in vitro or in vivo procedures, the success of PEG-induced fusion of sciatic or spinal axons and myelinated medial giant axons is measured by the restored conduction of action potentials through the lesion site, the presence of intact axonal profiles in electron micrographs taken at the lesion site, and/or the intra-axonal diffusion of fluorescent dyes across the lesion site. These and other data suggest that the application of polymeric fusiogens (such as our PEG solutions), possibly combined with a tissue adherent (such as our PEG hydrogels), could lead to in vivo treatments that rapidly and permanently repair cut or crushed axons in the PNS and CNS of adult mammals, including humans.

Key words: axotomy; axonal regeneration; membrane fusion; neurotrauma; nerve repair; polyethylene glycol

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Copyright © 1999 Society for Neuroscience  0270-6474/99/1972442-13$05.00/0

This article has been cited by other articles:

				J. S. Carp, A. M. Tennissen, D. L. Mongeluzi, C. J. Dudek, X. Y. Chen, and J. R. Wolpaw An In Vitro Protocol for Recording From Spinal Motoneurons of Adult Rats J Neurophysiol, July 1, 2008; 100(1): 474 - 481. [Abstract] [Full Text] [PDF]

				G. D. Bittner, T. Schallert, and J. D. Peduzzi Degeneration, Trophic Interactions, and Repair of Severed Axons: A Reconsideration of Some Common Assumptions Neuroscientist, April 1, 2000; 6(2): 88 - 109. [Abstract] [PDF]

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