A team of
scientists at UCSF has made a critical
discovery that may help in the
development of techniques to promote
functional recovery after a spinal cord
injury.
By stimulating
nerve cells in laboratory rats at the
time of the injury and then again one
week later, the scientists were able to
increase the growth capacity of nerve
cells and to sustain that capacity. Both
factors are critical for nerve
regeneration.
The study,
reported in the November 15 issue of the
Proceedings of the National Academy of
Sciences, builds on earlier findings in
which the researchers were able to
induce cell growth by manipulating the
nervous system before a spinal cord
injury, but not after.
Key to the
research is an important difference in
the properties of the nerve fibers of
the central nervous system (CNS), which
consists of the brain and spinal cord,
and those of the peripheral nervous
system (PNS), which is the network of
nerve fibers that extends throughout the
body.
Nerve cells
normally grow when they are young and
stop when they are mature. When an
injury occurs in CNS cells, the cells
are unable to regenerate on their own.
In PNS cells, however, an injury can
stimulate the cells to regrow. PNS nerve
regeneration makes it possible for
severed limbs to be surgically
reattached to the body and continue to
grow and regain function.
Regeneration
occurs because PNS cell bodies are
sensitive to damage to their nerve
processes, and they react by sending out
a signal that triggers the nerve fibers
to regrow, explains Allan Basbaum, PhD,
senior study author and chair of the
UCSF Department of Anatomy. "Apparently
this communication doesn't take place
within the CNS."
Scientists do
not yet know the biochemical cause for
the difference, he adds.
Basbaum's team
used nervous system manipulation
techniques to apply the principles of
PNS cell growth capability to CNS cells.
The researchers took advantage of an
unusual class of nerve fibers that has
both a PNS and a CNS branch. Previously,
the researchers had shown in animal
studies that an injury made to the
peripheral branch prior to a spinal cord
injury provided the essential
communication signal that enabled the
CNS branch to grow. But this only worked
if the PNS injury—which served as
priming for CNS cell growth—was made at
least a week before the CNS injury.
"Clearly this
would have no utility in clinical
situations, where treatments cannot be
made in anticipation of spinal cord
injury," says Basbaum.
Another
challenge the researchers faced was
stimulating CNS cells to grow beyond the
injury site and into healthy tissue,
which is essential to help regain
function.
"A PNS injury at
the time of spinal cord damage will only
promote growth of nerve fibers into the
spinal cord lesion, but not into the
tissue beyond it. This is because growth
capacity is enhanced, but it is not
sustained," he explains.
In the new
study, researchers evaluated the effect
of two peripheral nerve lesions
(injuries) in animals with spinal cord
injury. One lesion was made at the time
of the cord injury and a second was made
a week later. Both lesions were located
in the animals' sciatic nerve, which is
part of the PNS.
The researchers
found that the two "priming lesions" not
only promoted significant spinal cord
regeneration within the area of the
spinal cord injury, but more important,
the regenerating axons grew back into
normal areas of the spinal cord, where
the hope is that functional connections
can be reestablished. Axons are the
long, fragile, fibers that conduct
impulses between nerve cells in the
brain, spinal cord and limbs.
"Getting the
growth beyond the lesion is key. If we
can get those axons to grow even a few
centimeters past the lesion, they can
start sending signals and developing new
circuits throughout the body," says
Basbaum.
Basbaum adds
that timing is critical for successful
nerve regeneration. "There is a window
of opportunity just after the injury
when the potential for growth through
and beyond the lesion is greatest. If we
wait too long after an injury, the cells
revert back to their normal, no-growth
state. Plus, scar tissue begins to form,
making growth difficult."
"These findings
give us hope. The nervous system is
capable of being modified to a level
where we can achieve nerve fiber growth.
Ultimately, the goal is to promote
growth and sustain it long enough for
recovery of movement to occur in spinal
cord injury patients," he concludes.
Study co-authors
include first-author Simona Neumann,
PhD, and Kate Skinner, MD, both of UCSF.
The research was funded by the Roman
Reed Spinal Cord Injury Research Fund of
California and the National Institutes
of Health.
UCSF is a
leading university that consistently
defines health care worldwide by
conducting advanced biomedical research,
educating graduate students in the life
sciences, and providing complex patient
care.
Source:
University of California, San Francisco
Published on 14th
December 2005
