Scientists know that damaged neurons in the central nervous system of laboratory animals are able to regrow. Achieving the same results in the damaged human spinal cord, and getting the neurons to resume transmitting signals, are the ultimate goals of nervous system regeneration studies. A major drive is under way to understand the bodily mechanisms that control and encourage nerve growth, a key element in restoring function to paralyzed humans. One area of study focuses on nerve growth factors, natural substances that initiate and support new cell development, guide new or damaged nerves to appropriate targets, and assist in the maintenance of neuronal function.
Regenerating neurons need some kind of supporting structure, or substrate, on which to grow. Such a substrate should also direct the growing nerves to appropriate targets, allowing them to make connections that will transmit signals from one neuron to the next. A promising area of research focuses on natural and synthetic materials that may support and enhance regrowth of nerve cells and axons.
Growth of nerve cells and axons is but one part of the regenerative process. The growing axons need a protective covering, known as the myelin sheath, in order to transmit signals. To learn how to encourage remyelination of injured axons in the central nervous system, scientists are studying the peripheral nervous system, which has the innate ability to repair itself.
Schwann cells, which surround the axons of peripheral nerves, are responsible for myelination of those axons and may be key elements in peripheral nerve regeneration. By implanting pure Schwann cells, NINDS grantee Dr. Mary Bunge and her colleagues at the University of Miami in Florida, achieved extensive remyelination of central nervous system axons in newborn rats with a genetic myelin deficiency. This work proved that peripheral nerve cells could survive and function appropriately when implanted into the central nervous system. Dr. Bunge recently expanded her work on Schwann cells to their possible role in the repair and remyelination of spinal cord axons after traumatic injury.
Several NINDS-supported laboratories are exploring the use of implants of animal fetal nervous tissue to improve function in areas of the spinal cord damaged by trauma. Dr. John Houle, at the University of Arkansas in Little Rock, and Dr. Paul Reier, at the University of Florida in Gainesville, showed that implants of rat fetal spinal cord survived for extended periods when placed into the injured rat spinal cord. Such implants appeared to prevent or reduce scarring at the injury site, long believed to be an impediment to regeneration.
By transplanting fetal rat spinal cord into both newborn and adult rats with spinal lesions, Dr. Reier and NINDS grantee Dr. Barbara S. Bregman at Georgetown University in Washington, D.C., were able to promote survival of some damaged neurons. The investigators suggest that it is possible that the region of the graft served as a favorable environment through which spinal neurons could project. Or, the transplanted fetal tissue might itself be developing circuitry similar to that normally seen in the spinal cord.
Dr. Bregman has also implanted several different kinds of embryonic cells into rats with spinal cord lesions. All implants survived and, in the short term, were able to support the temporary survival of neurons. In the long term, however, only implants of embryonic spinal cord supported the survival of the injured cells. It may be that both environmental factors (such as nourishment from any implanted tissue) and mechanical factors (the terrain on which cells grow) are necessary for the growth of cells in spinal cord injury. Further study has identified the particular regenerative and transmitting characteristics of surviving fiber tracts. Such knowledge will be critical in planning both effective acute treatments and long-term rehabilitative programs.
The NINDS Neural Prosthesis Program supports and encourages research on the development of implantable devices to compensate electronically for lost sensory and motor functions.
One such device, developed by NINDS contractors Drs. Hunter Peckham, J. Thomas Mortimer, and others at Case Western Reserve University in Cleveland, Ohio, has recently moved out of the laboratory and into the clinical arena. This device restores an elementary form of hand grasp to quadriplegic patients who retain some ability to move their shoulders. The device uses implanted electrodes driven by signals from a microcomputer cued to perform its functions by changes in the angle of the shoulder opposite the affected hand. Several movements can be accomplished with this device including opening, closing and locking in place. Four clinical centers are evaluating the system.
Other scientists are testing implant materials for safety and effectiveness. Under an NINDS contract, Dr. Lois Robblee and others at EIC Corporation in Boston, Massachusetts, developed and patented an electrode coated with iridium oxide that can deliver more signal per unit area than conventional materials like platinum or stainless steel. Extremely small electrodes capable of stimulating discrete groups of nerve cells can now be produced, thus greatly increasing the degree of control exerted by implanted electronic devices. Dr. Robblee is assisting other NINDS investigators in applying iridium oxide to their stimulating electrodes. Dr. Ken Wise, an NINDS contractor at the University of Michigan in Ann Arbor, has developed an electrode probe with 5 stimulating sites. The next generation of this probe will have 16 stimulating sites on a shaft that is finer than a human hair. Arrays of such probes may permit highly selective stimulation within the central nervous system.
At the Huntington Research Institute in Pasadena, California, NINDS contractor Dr. William Agnew, after demonstrating that nerve degeneration in cat tissue could be produced by continued high-frequency electrical stimulation, has established safe limits for electrical currents used in implantable neural prostheses. He found that when damage occurs, it is caused by excessive neural activity, and not by a toxic effect of the implanted electrodes or electrical current. Dr. Agnew and his colleagues have developed both implantable and penetrating electrodes that stimulate neurons more selectively than earlier models. The investigators are continuing tests to determine how much stimulation is needed to produce the desired effect without causing damage to the affected nerves.
Under an NINDS contract with Simon Fraser University in Vancouver, British Columbia, Dr. Andy Hoffer is developing techniques to record the sensory information from the touch sensors in the hand. This information, still present in the peripheral nerves in spinal cord injured individuals, cannot reach the conscious level because the pathway to the brain is blocked in the spinal cord. Using sensory substitution techniques being developed by Dr. Clayton Van Doren, another NINDS investigator at Case Western Reserve University, the scientists hope to develop a sensory prosthesis that will restore some sense of touch.
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