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 second year of this project, we completed a key objective - the development 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, along with the initial characterization of the pathophysiological consequences of direct cranial primary blast injury (dcPBI) produced by COBIA. Our results have been submitted for publication. The most important findings include: (i) many of the pathophysiological consequences of bTBI in humans are reproduced in our model, including subarachnoid hemorrhage, widespread microvascular and neuronal abnormalities, persistent vestibulomotor and learning difficulties; (ii) dcPBI does not result in malignant cerebral edema, suggesting that observations of malignant cerebral edema in humans with bTBI may be due to dcPBI complicated by some other injury, e.g., hemorrhagic shock.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2010
- Accession Number
- ADA535037
Entities
People
- J.m. Simard
Organizations
- University of Maryland, Baltimore