2003 Director's Summary Synopsis

DEVELOPING STRATEGIES FOR NEUROPROTECTION
W. Dalton Dietrich, Ph.D. • Helen M. Bramlett, Ph.D. • Mary B. Bunge, Ph.D.

Understanding what happens to nerve cells and their connections after spinal cord injury (SCI) is essential knowledge in the search for a cure. Apart from the initial trauma, researchers have learned that various factors – like immune system responses and chemical reactions – lead to secondary injury. The Miami Project team includes members who focus on uncovering the intricacies of the cellular, chemical, and inflammatory responses that occur after injury. Using the knowledge gained, they strive to develop neuroprotection strategies that may be used in the acute and chronic injury settings.

It is known that inflammation is a mechanism for secondary injury. In a recent novel study, Drs. W. Dalton Dietrich and Mary Bartlett Bunge compared the effect of several inhibitors to iNOS, a chemical indicator for the various stages of inflammation. Previous experiments suggest that inhibition of iNOS results in the reduction of nerve cell damage. This recent study showed that antisense technology is more effective and appears to provide a more selective inhibition than other iNOS inhibitors. This molecular approach, which inhibits gene expression, is also potentially less toxic perhaps making it a better choice for clinical application. Antisense strategies are being developed for many disorders and are in clinical trial.

Other research provides additional knowledge pertinent to future clinical treatments. Researchers have found that hypothermia affects the inflammatory processes in secondary injury and provides some protection to the nervous system. Recent research also suggests that female hormones may be neuroprotective. The purpose of this Miami Project study by Drs. Helen Bramlett and W. Dalton Dietrich was to directly compare the effects of hypothermia in males versus females. The results suggest that hypothermia treatment provided no additional benefit to females. In future clinical trials, it will be important to consider the differences between males and females when evaluating the results of neuroprotective and regenerative strategies.

Synopsis Publications

 Pearse DD, Chatzipanteli K, Marcillo AE, Bunge MB, Dietrich WD (2003) Comparison of iNOS inhibition by antisense and pharmacological inhibitors after spinal cord injury. J Neuropathol Exp Neurol 62:1096-1107.

 Suzuki T, Bramlett HM, Dietrich WD (2003) The importance of gender on the beneficial effects of posttraumatic hypothermia. Exp Neurol 2003 Dec;184(2):1017-26.