Stephen J. A. Davies, Ph.D.
Assistant Professor
Undergraduate School
Sussex University, Brighton, UK
Ph.D.
University College London England
Primary Neurosurgical Interests
Research: CNS regeneration; molecular and cell biology of axon regeneration
and glial scar formation in the injured adult central nervous system
Contact Information
Baylor Faculty Center
1709 Dryden Road, Suite 750
Houston, TX 77030
Phone: 713-798-6249
Fax: 713-798-3739
New In Research
Molecular and cell biology of repairing the traumatically injured adult mammalian central nervous system.
Stephen Davies, Ph.D.,
Assistant Professor, Departments of Neurosurgery and Neuroscience, Baylor
College of Medicine, Houston, TX
When axons are severed by traumatic injury to the adult mammalian central nervous system, the surviving portion of the axon still connected to the cell body often sprouts but ultimately fails to regenerate across the site of injury back to its original target, resulting in a loss of nervous system function. Traumatic CNS injuries also result in the loss of glia vitally important for maintaining the structure and function of the nervous system. The brain and spinal cord often reacts to inflammation and the loss of glia at sites of injury by rapidly forming a fibrous meshwork of dense scar tissue directly in front of the cut ends of axons that are attempting to regenerate. Glial scar tissue is also rich in molecules such as chondroitin sulfate proteoglycans (CSPGs), semaphorins and ephrins that are known to be inhibitory to axon growth and thus CNS scar tissue presents a combined physical and molecular barrier to axon regeneration(1).
My research team at Baylor is therefore developing two, complementary approaches to repairing the injured adult CNS: 1.) suppression or removal of glial scar tissue to promote axon growth across sites of injury and 2.), development of neural precursor (stem cell-like) technologies to generate different types of central nervous system glia suitable for repairing the injured brain and spinal cord. We have recently shown that a naturally occurring antagonist of scar formation, a small leucine rich proteoglycan called decorin, is highly effective at suppressing inflammation, synthesis of CSPGs and fibrous scar formation when infused into acute spinal cord injuries in rats(2). More importantly decorin infusion permitted the rapid growth of axons across sites of injury in just 4 days. We are also interested in the ability of decorin to induce the expression of enzymes such as the serine protease plasmin in the injured CNS(3) that potentially have the ability to not only degrade scar tissue but promote plasticity of neural circuitry. In a parallel line of research, we have also shown that a specific sub-type of astrocyte derived from embryonic glial restricted precursor cells (GRPs) can promote a high efficiency of axon regeneration and functional recovery after transplantation to adult spinal cord injuries(4). The use of GRP technology not only allows us to develop new cell types for repairing the adult CNS but also to investigate the basic glial cell biology of the normal and injured central nervous system.
Through gaining a greater understanding of the underlying molecular and cellular mechanisms that govern both failure and success of the adult CNS to regenerate our ultimate goal is to provide a clinically relevant strategy to promote efficient tissue repair and functional recovery of the injured human central nervous system.
Novel stem cell technology promotes recovery after spinal cord injury
Selected Publications
Tang X, Davies JE and Davies SJA (2003). Changes in distribution, cell associations and protein expression levels of NG2, Neurocan, Phosphacan, Brevican, Versican V2 and Tenascin-C during acute to chronic maturation of spinal cord scar tissue. Journal of Neuroscience Research:71(3):427-444.
Davies J.E., Tang X., Denning J.W., Archibald S.J., and Davies S.J.A. (2004) Decorin suppresses neurocan, brevican, phosphacan and NG2 expression and promotes axon growth across adult rat spinal cord injuries. European Journal of Neuroscience. 19:1226-1242.
Davies J.E., Tang.X, Bournat J.C. and Davies S.J.A. (2006) Decorin promotes plasminogen/plasmin expression within acute spinal cord injuries and by adult microglia in vitro. Journal of Neurotrauma 23(3-4):397-408.
Davies J.E., Huang C.X., Proschel C., Noble M., Mayer-Proschel M. and
Davies S.J.A. (2006) Astrocytes derived from glial restricted precursors
promote spinal cord repair Journal of Biology 5:7.
(Online Open Access http://jbiol.com/content/5/3/7
)