Faculty Book
MARY BARTLETT BUNGE, PH.D.
Christine E.
Lynn Distinguished Professor in Neuroscience
Professor,
Cell Biology & Anatomy, Neurological Surgery and
Neurology
Development of combination
strategies to repair the injured spinal cord
Research Interests
The goals in my
laboratory fall into two categories: 1) protecting the
spinal cord from secondary damage after the initial injury,
and 2) fostering regeneration of axons across and beyond the
area of injury. This has been an objective in my laboratory
since moving to Miami in 1989. The neuroprotective
strategies that we are employing to reduce the amount of
secondary tissue loss involve interfering with the action of
damaging cytokines and modifying the inflammatory response.
To improve regeneration of axons after spinal cord injury,
we are investigating increases in cyclic AMP levels,
interference with proteoglycans (molecules that inhibit
axonal growth), transplantation of Schwann cells and/or
olfactory ensheathing glia, and genetic engineering of these
cells before transplantation to improve their neurotrophic
factor-secreting capability. We have also initiated a new
microarray study to explore gene differences between neurons
that are able to regrow onto a cellular bridge placed in the
area of injury and those that do not grow onto the bridge.
Because the reactions of the tissue to spinal cord injury
are many and varied, I espouse the concept that a
combination strategy will be necessary to improve outcome
after spinal cord injury.
A main contribution of my laboratory
has been to introduce the novel use of a cellular (Schwann
cell) bridge across a complete transection gap in the adult
rat spinal cord. We have tried a number of combination
strategies with that, and the spinal cord injured animal has
improved. For example, when neurotrophins, brain-derived
neurotrophic factor and neurotrophin-3, are introduced along
with Schwann cell bridges, there are more regrowing fibers
on the bridge and there is an increased variety of fibers on
the bridge, including some from distant neuronal somata
positioned in the brain stem. Fibers also exit the bridge
after a combination strategy. We have found a number of
situations in which the fibers can be encouraged to leave
the bridge, such as the transplantation of olfactory
ensheathing glia at either end of the Schwann cell bridge.
This combination also led to long-distance axonal
regeneration in the adult rat cord. We have also started to
test combination strategies in a spinal cord contusion
model. We have demonstrated that a combination strategy is
consistently more effective than a single one.
Ramón-Cueto A, Plant GW, Avila J and
Bunge MB (1998) Long-distance axonal regeneration in the
transected adult rat spinal cord is promoted by olfactory
ensheathing glia transplants. J Neurosci 18:3803-3815. [Abstract]
Plant GW, Bates ML, Bunge MB (2001)
Inhibitory proteoglycan immunoreactivity is higher at the
caudal than the rostral Schwann cell graft-transected
spinal cord interface. Molec Cell Neurosci 17:471-487. [Abstract]
Bunge MB (2001) Bridging areas of
injury in the spinal cord. Neuroscientist 7:325-339. [Abstract]
Takami T, Oudega M, Bates ML, Wood
PM, Kleitman N, Bunge MB (2002) Schwann cell but not
olfactory ensheathing glia transplants improve hindlimb
locomotor performance in the moderately contused adult rat
thoracic spinal cord . J Neurosci 22:6670-6681. [Abstract]
Blits B, Oudega M, Boer GJ, Bunge
MB, Verhaagen J (2003) Adeno-associated viral
vector-mediated neurotrophin gene transfer in the injured
adult rat spinal cord improves hindlimb function.
Neuroscience 118:271-281. [Abstract]
Bunge MB, Pearse DD (2003)
Transplantation strategies to promote repair of the
injured spinal cord. J Rehab Res Dev 40 [Abstract]
Pearse DD, Pereira FC, Marcillo AE,
Bates ML, Berrocal YA, Filbin M, Bunge MB (2003) Elevation
of cyclic AMP enhances regeneration and improves
behavioral recovery in Schwann cell-grafted animals after
spinal cord injury [Abstract].
Last updated June 9,
2004
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