Accession Number:

ADA610917

Title:

Glyburide - Novel Prophylaxis and Effective Treatment for Traumatic Brain Injury

Descriptive Note:

Final rept. 7 Jul 2008-30 Jun 2014

Corporate Author:

BALTIMORE UNIV MD

Personal Author(s):

Report Date:

2014-09-01

Pagination or Media Count:

75.0

Abstract:

Addressing specific objectives of the project we developed, constructed and implemented a cranium only blast injury apparatus COBIA for production of standardized and reliable rat model of dose dependent blast-TBI bTBI to study the direct transcranial effects of blast on the brain, independent of indirect transthoracic effects Detailed anatomical evaluation revealed that cranium only blast impacts brain-blood barrier transiently, immediately after the blast. Long term impact of the blast is manifested predominantly in the brain tissues at the density boundaries, with elevated markers of the neuroinflammation, neurodegeneration and neuronal cell death. COBIA bTBI resulted in the transient vestibulomotor abnormalities and long term spatial memory deficits. After COBIA bTBI Sur1 and TRPM4 RNA and protein up-regulation was detected as early 4 hours after the blast consistent with de-novo expression of the SUR1 regulated NCCa-ATP channel Studies including GLP-compliant protocol with chronic administration of the SUR1 antagonist showed that post-bTBI Glyburide does not alter blast-induced long term cognitive deficits but improves anxiety-like behavior. In contrast prophylactic treatment with Glyburide improved performance in spatial memory task related to the hippocampal function. Study on the human volunteers showed that Glyburide is safe drug to be used for potential prophylaxis against blast TBI.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE