Rapid induction of functional and morphological continuity between severed ends of mammalian or earthworm myelinated axons

April B. Lore, Jeffery A. Hubbell, David S. Bobb, Martis L. Ballinger, Keisha L. Loftin, Jeffory W. Smith, Mark E. Smyers, Habacuc D. Garcia, George D. Bittner

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

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 vive 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 vive 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 vive treatments that rapidly and permanently repair cut or crushed axons in the PNS and CNS of adult mammals, including humans.

Original languageEnglish
Pages (from-to)2442-2454
Number of pages13
JournalJournal of Neuroscience
Volume19
Issue number7
StatePublished - Apr 1 1999
Externally publishedYes

Fingerprint

Oligochaeta
Axons
Mammals
Nerve Tissue
Hydrogels
Hydrogel
Fluorescent Dyes
Connective Tissue
Action Potentials
Electrons

Keywords

  • Axonal regeneration
  • Axotomy
  • Membrane fusion
  • Nerve repair
  • Neurotrauma
  • Polyethylene glycol

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Lore, A. B., Hubbell, J. A., Bobb, D. S., Ballinger, M. L., Loftin, K. L., Smith, J. W., ... Bittner, G. D. (1999). Rapid induction of functional and morphological continuity between severed ends of mammalian or earthworm myelinated axons. Journal of Neuroscience, 19(7), 2442-2454.

Rapid induction of functional and morphological continuity between severed ends of mammalian or earthworm myelinated axons. / Lore, April B.; Hubbell, Jeffery A.; Bobb, David S.; Ballinger, Martis L.; Loftin, Keisha L.; Smith, Jeffory W.; Smyers, Mark E.; Garcia, Habacuc D.; Bittner, George D.

In: Journal of Neuroscience, Vol. 19, No. 7, 01.04.1999, p. 2442-2454.

Research output: Contribution to journalArticle

Lore, AB, Hubbell, JA, Bobb, DS, Ballinger, ML, Loftin, KL, Smith, JW, Smyers, ME, Garcia, HD & Bittner, GD 1999, 'Rapid induction of functional and morphological continuity between severed ends of mammalian or earthworm myelinated axons', Journal of Neuroscience, vol. 19, no. 7, pp. 2442-2454.
Lore AB, Hubbell JA, Bobb DS, Ballinger ML, Loftin KL, Smith JW et al. Rapid induction of functional and morphological continuity between severed ends of mammalian or earthworm myelinated axons. Journal of Neuroscience. 1999 Apr 1;19(7):2442-2454.
Lore, April B. ; Hubbell, Jeffery A. ; Bobb, David S. ; Ballinger, Martis L. ; Loftin, Keisha L. ; Smith, Jeffory W. ; Smyers, Mark E. ; Garcia, Habacuc D. ; Bittner, George D. / Rapid induction of functional and morphological continuity between severed ends of mammalian or earthworm myelinated axons. In: Journal of Neuroscience. 1999 ; Vol. 19, No. 7. pp. 2442-2454.
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