By Vikki Franklin

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See related story in the Dec. 14, 1999, issue of the Lexington Herald-Leader.

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In May 1999, UK added to its growing list of centers focused in the neurosciences the Spinal Cord and Brain Injury Research Center (SCoBIRC), as UK moves toward top-20 status among public institutions. UK already boasts several centers, including the nationally recognized Sanders-Brown Center on Aging, and recently was awarded a $5 million dollar National Institutes of Health (NIH) grant for the establishment of the Morris K. Udall Parkinson’s Disease Research Center of Excellence.

The goal of UK’s SCoBIRC is to understand the nature of severe injuries to the spinal cord and brain, and to develop clinical approaches for improving the recovery of patients who have suffered such injuries.

In addition to helping launch the center, the trust also supports the research of 14 UK investigators who are tackling spinal cord injury on three fronts: minimizing the damage following injury, promoting the restoration of neural circuitry, and improving function in the patient with spinal cord injury. UK investigators have parlayed support from the trust into NIH funding. Without such funding from the trust, investigators would not have been able to develop preliminary results necessary to secure federal funding. Also, such support is, and continues to be, critical in attracting top-notch researchers to the center.

Initial injury to the spinal cord often is relatively minor, but secondary events amplify this damage and greatly worsen the patient’s ultimate outcome. UK investigators are examining the mechanisms involved in neural damage and subsequent degeneration, and they are testing strategies to minimize this secondary damage. Ongoing research projects producing promising results include:

• Joe Springer, Ph.D., associate professor, and Pam Knapp, Ph.D., assistant professor, both of the Department of Anatomy and Neurobiology, UK College of Medicine, found that a cell death pathway, the "caspase-3 apoptotic cascade," is activated rapidly within neurons near the injury site, but activated much later in another cell type, oligodendroglia, adjacent to and distant from the injury site. Inhibition of the apoptotic cascade represents a novel therapeutic target to minimize the damage following spinal cord injury. The results of this research project enabled Springer to apply for a five-year, $1.3 million NIH grant that would examine ways to intervene in the cell death pathway. The grant has not been awarded yet, but Springer’s project is very competitive. Springer also received funding from a biotechnology company to test a compound using the spinal cord injury model he and Knapp developed.
• Springer, Knapp, Sonia Carlson, Ph.D., associate professor, and Kurt Hauser, Ph.D., associate professor, all of the Department of Anatomy and Neurobiology, UK College of Medicine, who have been awarded grants from the trust independently,

are applying for a multi-million dollar NIH program project grant in February 2000. Without the results obtained from the KSCHIRT research grants, the researchers could not have applied for the NIH grant.

• The regrowth of damaged axons and the re-establishment of appropriate neuronal connections is essential for functional recovery following injury to the spinal cord. With the support of the trust, UK was able to recruit George Smith, Ph.D., associate professor, Department of Physiology, UK College of Medicine, from the University of Texas Southwestern Medical Center in Dallas. Smith, who is nationally known for his use of state-of-the-art techniques to develop novel therapeutic approaches for spinal cord injury, uses gene therapy to increase nerve growth factors in the injured spinal cord. This promotes the regrowth of the damaged axons. Smith joined UK with a $700,000 NIH grant to study gene therapy for spinal cord regeneration. He also recently received a four-year, $1.2 million NIH grant to study new methods to repair damage to the nervous system.

• Other investigators, including Tim McClintock, Ph.D., associate professor, Department of Physiology, and Diane Snow, Ph.D., assistant professor, Department of Anatomy and Neurobiology, UK College of Medicine, are exploring the mechanisms used to guide axons to their proper target. This research is bringing us closer to the goal of restoring the neuronal circuitry after spinal cord injury. McClintock recently received an $800,000 NIH grant to identify novel methods to

study genes in the brain and spinal cord. The results from his trust-sponsored studies were the basis for his NIH grant.

• To facilitate movement of paralyzed individuals, James Abbas, Ph.D., assistant professor, UK Center for Biomedical Engineering, is developing neural prosthetics. Computer-controlled electrical stimulation of muscles is used to facilitate recovery following spinal cord injury. The neural prosthetics allow a paralyzed individual to initiate and control limb movement with the aid of a laptop computer and joystick. This helps prevent muscle loss following injury.
• With results from a research project supported by a trust grant, Stephen Scheff, Ph.D., professor, Department of Anatomy and Neurobiology, UK College of Medicine, applied for a four-year, $1 million NIH grant to examine the use of novel drugs to protect the brain following traumatic brain injury. Because of the trust’s support, Scheff’s grant proposal is very competitive.
• The ongoing research and support of the trust have attracted additional private support. For example, in July 1999, Cardinal Hill Rehabilitation Hospitals, headquarters for the Kentucky Easter Seal Society, pledged $2 million to UK to establish a new endowed chair and two new endowed professorships in neurorehabilitation. The funds from Cardinal Hill will be matched by the Research Challenge Trust Fund. The gift will be used to support the Cardinal Hill Rehabilitation Hospital Chair in Neurorehabilitation and professorships, which will

allow the appointees the opportunities to pursue research in neurorehabilitation and involve patients at Cardinal Hill and UK in these research programs.

UK’s SCoBIRC was created as a result of a five-year pledge of $2.5 million from the trust to UK. The gift establishes three endowed chairs and an endowment to support postdoctoral and graduate student fellowships in spinal cord and brain injury research. UK is matching $2 million of the gift. The funds will support faculty salaries and graduate student and postdoctoral researcher training. UK will provide additional support for start-up costs and faculty salaries. Additional trust contributions from 1996-97 and 1997-98 also will support endowed chairs for faculty. This funding will enable SCoBIRC to continue its recruitment efforts. James Geddes, Ph.D., associate professor, Department of Anatomy and Neurobiology, UK College of Medicine, is serving as director.