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 4th year of this project we performed detailed anatomical evaluation of the cells de novo expressing SUR1 protein, and quantitative measurements of the SUR1 and TRPM4 RNA and proteins after blast injury. We compared cellular responses of the brain to direct delivery of the blast wave to the brain via cranial exposure versus indirect delivery of the blast wave to the brain via thoracic exposure. The most important findings include: (i) cranium only (COBIA) blast impacts brain tissues at density boundaries and brain-blood barrier is minimally altered, (ii) after COBIA injury Sur1 and TRPM4 RNA and protein upregulation is detected as early 4 hours after the blast, (iii) thoracic delivery of the blast results in distinct cerebral perivascular inflammation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2012
- Accession Number
- ADA573506
Entities
People
- J. M. Simard
Organizations
- University of Maryland, Baltimore