2 research outputs found
Rapid induction of functional and morphological continuity between severed ends of mammalian or earthworm myelinated axons
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
Ca21-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.These studies were funded by National Institutes of Health Grants NS31256 and
HD31484, a Texas Advanced Technology grant to G.D.B., personal funds of G.D.B.,
and National Science Foundation Grant BES-9696020 to J.A.H.Neuroscienc
Rapid induction of functional and morphological continuity between severed ends of mammalian or earthworm myelinated axons
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
Ca21-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.These studies were funded by National Institutes of Health Grants NS31256 and
HD31484, a Texas Advanced Technology grant to G.D.B., personal funds of G.D.B.,
and National Science Foundation Grant BES-9696020 to J.A.H.Neuroscienc