Panter Laboratory

The laboratory of S. Scott Panter focuses on mechanisms of cellular injury following stroke or trauma, especially the component of brain or spinal cord injury caused by the erythrocyte protein hemoglobin. Cell culture studies performed in his laboratory have described hemoglobin-dependent neurotoxicity and warned about possible toxicities associated with the administration of hemoglobin-based oxygen carriers to stroke or trauma patients. These results were confirmed in two clinical trials. Dr. Panter's laboratory continues to pursue models of hemoglobin-based neurological injury. He has developed a gerbil model of intracerebral hemorrhage and also utilizes a rat model of subarachnoid hemorrhage. In addition, Dr. Panter's laboratory has a significant interest in iron-catalyzed tissue injury, which is most likely the mechanism of hemoglobin-dependent cellular toxicity. This laboratory has been involved in the development of a new generation of iron chelators that may be effective in the treatment of stroke, traumatic brain injury, or ischemia-reperfusion injury.

Most recently, his laboratory has also been administering chelators directly to the brain via an intranasal route, bypassing the blood brain barrier. Using the high-affinity iron chelator, deferoxamine administered before stroke, tissue damage following stroke in rats can be reduced by 60%. Patients that would benefit from this "pharmacological preconditioning" would be those with a high risk for stroke-patients undergoing coronary artery bypass surgery or other vascular surgeries. Deferoxamine can also be administered after stroke in rats, reducing tissue damage by 50%. Intranasal deferoxamine may also be effective in the future for the treatment of neurodegenerative diseases that may have an iron-dependent component, such as Alzheimer's and Parkinson's disease, amyotrophic lateral sclerosis or multiple sclerosis.

Finally, Dr. Panter's laboratory has been recently involved in characterizing the first model of a controlled, cortical impact-induced traumatic brain injury in swine. There are few large-animal models of traumatic brain injury, and these models are particularly relevant to the Department of Veterans Affairs, where Dr. Panter's lab is located. Eventually, this model will be useful for testing pharmacological agents that can be used to ameliorate tissue damage following trauma and improve long-term outcome.

Collaborators:
Geoffrey T. Manley MD, PhD - Traumatic brain injury
Phillip R. Weinstein MD - Stroke
Raymond A. Swanson MD (Neurology) - Oxidative injury in brain
Jialing Liu PhD - Cognitive deficits and recovery following stroke or intracerebral hemorrhage
Raymond F. Regan MD - Neurotoxicity of hemoglobin
Paul D. Dragsten PhD and Bo E. Hedlund PhD - Iron chelators
Linda J. Noble PhD - Traumatic brain injury and hemoglobin's contribution to injury
William H. Frey II PhD - Intranasal Drug Delivery and Stroke