2004 Directors' Summary Synopsis

PATHOPHYSIOLOGY AND NEUROPROTECTION

The goal of research efforts related to pathophysiology and neuroprotection is to understand specific injury processes that create the damage in the spinal cord and prevent it from repairing. As various injury mechanisms are better understood, specific interventions to block them are being designed to promote recovery of function.

This year, Dr. Michael Norenberg and colleagues continued studies of human postmortem spinal cord tissue. The current collection of 180 spinal cords represents various causes of injury and times post-injury. The Miami Project’s most recent study of the tissue looked at the types of cells that replace the damaged tissue. The research showed an extraordinarily high incidence of schwannosis in human SCI. Schwannosis is a phenomenon where Schwann cells and axons, presumably from the peripheral nervous system, migrate into the damaged spinal cord. It is unclear what impact schwannosis has on regeneration, so further research is needed to determine whether it contributes to inhibition of regeneration.

In addition to the study of human post-mortem tissue, Miami Project scientists are designing studies to understand the role that inflammation has in tissue damage after traumatic SCI. Dr. John Bethea has shown that injury activates NF-kappaB within various cells in the spinal cord. NF-kappaB is a cell-signaling factor that plays a pivotal role in regulating inflammation and possibly cell death. In a recent study, Dr. Bethea identified a protein (TNAP) that suppresses NF-kappaB. Based on this finding, further work to develop and test a new neuroprotective treatment is planned.

Other Miami Project studies by Drs. W. Dalton Dietrich and Helen Bramlett are helping to clarify the role that inflammation has in secondary injury processes. Their studies are also examining the potential benefit of a clinically relevant treatment strategy using mild hypothermia. Based on current data, therapeutic hypothermia may protect brain and spinal cord tissue following injury by regulating harmful inflammatory processes.

As basic science studies are pointing to the potential benefits of inducing hypothermia, clinicians like neurosurgeon Dr. James Guest are eager to understand how feasible and safe this treatment strategy would be in humans. The safety of hypothermia is a concern since it has been associated with post-operative wound infection and increased blood loss. To gain a beginning understanding of the potential untoward effects of hypothermia, Dr. Guest looked back at operating room records to determine whether post-operative complications were linked to the natural cooling that occurs during surgery. He found that temperature did not influence the amount of blood loss, however, the length of exposure to mild hypothermia was associated with an increased incidence of wound infection. These observations suggest that mild hypothermia used as a potential neuroprotective strategy during spinal surgery appears to be reasonably safe, but care should be taken to minimize the duration of the cooling to prevent post-operative complications. Further study is also required to determine if inducing hypothermia results in improved neurological recovery in the patient.