[TMIC] FYI - New Way To Promote Nerve Growth
RCookHook(AT)aol.com
Tue, 1 Jun 1999 12:53:28 EDT
Contact: Susan McGreevey smcgreevey(AT)partners.org 617-724-2764
Massachusetts General Hospital New Technique
Induces Growth Across Spinal Cord Injury Using a totally new approach,
researchers at the Massachusetts General
Hospital (MGH) have for the first time induced the growth of severed
adult mammalian spinal cord fibers across the site of
the injury. The animal study appearing in the May issue of Neuron is
the first to report repairing such an injury without the
use of implanted cells or tissues to bridge the severed fibers. In
addition, the findings call into question current assumptions
about barriers to spinal cord regeneration. "We have actually tricked
nerve cells into growing beyond the area of a spinal
cord injury by switching them into an actively growing state," says
Clifford Woolf, M.D., Ph.D., of the Neural Plasticity
Research Group in the MGH Department of Anesthesia and Critical Care,
who led the study. "While the particular
approach we used cannot be applied in humans, it points us in a
promising new direction. The question is no longer
whether spinal cord regeneration is possible but how it will be
achieved." It has been known for years that severed nerve
fibers in the adult spinal cord cannot regenerate. However, damaged
peripheral nerves - those in the extremities - can heal
themselves. What has intrigued and frustrated researchers is the fact
that the fibers making up one sensory system in the
spinal cord come from the same cells as do the fibers in peripheral
nerves. These sensory nerve cells or neurons have two
long processes, called axons, that extend from the main cell body
located next to the spinal cord. One axon, the central
branch, joins the spinal cord and travels to the brain; the other, the
peripheral branch, travels out to the extremities. If the
peripheral branch of these cells is injured, it regenerates; if the
central branch is injured, it does not. Because two branches
of the same cell exhibit totally different healing capacities, most
researchers thought the difference must lie in the
environments surrounding the branches, which are very different.
Previous attempts to repair severed spinal cords focused
on implants of peripheral nerve-tissue "bridges," reproducing cellular
environments similar to that of peripheral nerves, or
grafts made from embryonic spinal cords, which have the capacity to
regenerate. The success of those efforts, Woolf says,
has been marginal. In the current study, Woolf and his colleague Simona
Neumann, PhD, questioned the assumption that
environment made the key difference. "Perhaps, we thought, the question
should be whether or not the cell was receiving
molecular signals from the injury site to stimulate regenera-tion.
Maybe damage to the central branch does not switch on
these growth signals, while damage to the peripheral branch does." To
test this hypothesis, the researchers devised a
groups of experiments in rats to see whether injury to the peripheral
branch of a nerve made a difference to regeneration of
the central branch, which would indicate whether molecular growth
signals were important. When they injured the
peripheral branch of the sciatic nerve (the main sensory nerve to the
leg) at the same time as they damaged the animal's
spinal cord, the results were striking. Numerous axonal fibers sprouted
and grew in the spinal cord around and directly into
the injured area. The fibers, which extended from the lower segment of
the spinal cord, did not grow all the way across the
injury into the upper segment. In comparison, however, damaging the
spinal cord without the peripheral nerve injury
produced no growth at all into the injured area. Injuring the
peripheral nerve a week before the spinal cord injury produced
even more dramatic results. Axonal fibers grew either completely
through or around the injured area and some extended
into the upper portion of the spinal cord. "A complete regeneration
across the injury site had been achieved," Woolf says.
"We have shown that if we can switch these cells into a state where
they can grow, they will grow - even the central
branch," he adds. "The problem was not that the adult central nervous
system is hostile territory for growth, as previously
thought. The problem is getting the injured cells to grow. Now we need
to identify the molecular signals that induce this
growth and the genes on which they act. If we can find ways to turn
those signals on without the peripheral nerve injury and
apply them soon after patients suffer spinal cord injury, we may
finally achieve what was once seen as an unreachable
goal: reconnection of a severed spinal cord." The study was supported
by a grant from the International Spinal Research
Trust.