Glyburide - Novel Prophylaxis and Effective Treatment for Traumatic Brain Injury
Abstract
The overall subject of this project is blast-traumatic brain injury (blast-TBI) and the role of the SUR1-regulated NCCa-ATP channel in blast-TBI. The specific objectives of this project include: (1) develop a standardized rat model of blast-TBI to study the direct transcranial effects of blast on the brain, independent of indirect transthoracic effects; (2) determine the role of the SUR1-regulated NCCa-ATP channel in blast-TBI; (3) in normal human volunteers, determine the safety of the SUR1 blocker, glyburide, as it might be used as prophylaxis against blast-TBI. During the first year of this grant, we completed a key objective--the development, construction and implementation of a cranial-only blast injury apparatus (COBIA) for production of reliable, repeatable, "dose-dependent" blast-TBI, independent of transthoracic mechanisms of injury to the brain. Using COBIA, we began characterizing the pathophysiological consequences of blast-TBI, with early results suggesting the novel observation that blast-TBI can produce fatal neurogenic pulmonary edema independent of blast injury to the thorax. We also began characterizing the effect of blast-TBI on the SUR1-regulated NCCa-ATP channel. Early results suggest the novel finding that SUR1 is abundantly upregulated in neurons and oligodendrocytes, further strengthening the rationale for prophylaxis and treatment using the SUR1 inhibitor, glyburide.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 06, 2009
- Accession Number
- ADA538679
Entities
People
- J. M. Simard
Organizations
- University of Maryland, Baltimore