Reeve-Irvine Scientific Research
Enhancing Regeneration of Damaged Nerve Cells
The loss of motor and sensory function following spinal cord injury is due to the interruption of the long nerve connections (tracts) between the brain and the spinal cord. Accordingly, full restoration of function will require that we find ways to induce these damaged connections to regenerate. The reasons for regenerative failure include:
- loss of the intrinsic capacity for growth by neurons due to shutting down key genes that are required for growth;
- presence of inhibitory molecules in the myelin sheath of axons that blocks regenerative growth;
- the development of a dense glial scar at the injury site that contains molecules that are strongly inhibitory to growth; and
- lack of a tissue environment that is supportive for growth.
Each of these represent potential targets for therapy following spinal cord injury. For example, one approach is to stimulate growth by turning on key genes, including "growth factors", that are required for regeneration and the formation of connections between neurons (known as "synapses"). Of particular interest are "activity-regulated genes" that can be induced by manipulating neuronal activity (Os Steward, Carl Cotman, Christine Gall).
An important area of regeneration research involves identification of inhibitory molecules present in the myelin sheath, and the receptors on nerve cells that mediate growth inhibition (Os Steward, Ranjan Gupta, Melanie Cocco). This identification is the basis for developing small synthetic molecules that could block growth inhibition, and thus promote regeneration.
Finally, to address the problem of a lack of a tissue environment that is supportive for axon growth, several RIRC investigators are exploring how transplants might be used to support regeneration. Approaches include transplants of peripheral nerve tissue (peripheral nerves are capable of some regeneration) Schwann cells (the cells in the peripheral nerve that express molecules supportive for growth), matrices made up of molecules from lower species (fish) that can regenerate, and stem cells (Ranjan Gupta, Aileen Anderson, Hans Keirstead, Lisa Flanagan, and Os Steward).
These studies in an SCI context are supplemented by studies of lower vertebrates (fish and frogs) that are capable of nerve and tissue regeneration (Ron Meyer, Susan Bryant) and studies of areas of the brain that are capable of "neurogenesis" (the birth of new nerve cells) (Ann Calof).