Paralysis research: Promoting nerve fiber protection, growth and functional recovery by cyclic AMP and cell transplantation.
Extract: In a recent study we reported that levels of the intracellular signalling molecule, cyclic adenosine monophosphate (cAMP), are important in facilitating spinal cord injury (SCI) repair. Following is a brief summary of previous findings that led us to examine cAMP levels after SCI and to test the hypothesis that elevating the level of cAMP could improve nerve fiber growth and functional outcome. We employed in these experiments an incomplete SCI model, whereby a specific weight is dropped from a consistent height onto the exposed surface of the spinal cord at the thoracic (chest) level to induce a bruising type injury. The elevation of cAMP was used in combination with the transplantation of a type of peripheral nerve cells, called Schwann cells. Lastly, the implications of our findings for human SCI repair are discussed.Regeneration of neurons within the central nervous system following SCI is limited by the presence of inhibitory molecules and a lack of growth supporting molecules at the injury site, by the physical barrier created by a scar that forms around the injury site, and by a reduced intrinsic capacity for growth in neurons that occurs after development and maturation. Transplantation of cells from the peripheral nervous system -- Schwann cells -- can be used to replace lost tissue within the injured spinal cord and form an environment conducive for nerve fiber re-growth. Importantly, Schwann cell transplantation is clinically relevant because of the feasibility of autologous transplantation from harvested peripheral nerves for use in human SCI. However, Schwann cell grafts do not enable regenerated nerve fibers to grow out of the transplant, and they elicit only a weak response from neurons from the brain that are important for voluntary control of walking. These limitations have stimulated the development of combination strategies that will improve the ability of Schwann cells to promote repair of the injured spinal cord and enhance functional recovery.
Pearse
Damien D
DD
The Miami Project to Cure Paralysis, University of Miami School of Medicine, 1095 NW 14th Terrace, Miami, FL 33136, USA.
Bunge
Mary Bartlett
MB