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

The inability to rapidly restore the loss of function that results from sev erance (cutting or crushing) of PNS and CNS axons is a severe clinical prob lem. As a novel strategy to help alleviate this problem, we have developed in vitro procedures using Ca2+-free solutions of polyethylene glycol (PEG s olutions), which within minutes induce functional and morphological continu ity (PEG-induced fusion) between the cut or crushed ends of myelinated scia tic or spinal axons in rats. Using a PEG-based hydrogel that binds to conne ctive tissue to provide mechanical strength at the lesion site and is nonto xic to nerve tissues in earthworms and mammals, we have also developed in v ivo 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 pr ocedures, the success of PEG-induced fusion of sciatic or spinal axons and myelinated medial giant axons is measured by the restored conduction of act ion potentials through the lesion site, the presence of intact axonal profi les in electron micrographs taken at the lesion site, and/or the intra-axon al diffusion of fluorescent dyes across the lesion site. These and other da ta suggest that the application of polymeric fusiogens (such as our PEG sol utions), possibly combined with a tissue adherent (such as our PEG hydrogel s), could lead to in vivo treatments that rapidly and permanently repair cu t or crushed axons in the PNS and CNS of adult mammals, including humans.