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Glyburide-Novel Prophylaxis and Effective Treatment for Traumatic Brain Injury

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Annual rept. 7 Jul 2010-6 Jul 2011

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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 third year of this project, we completed a key objective the evaluation of our cranial-only blast injury apparatus COBIA as it relates to the effect of blast exposure on short term vestibulomotor performance and on long term cognitive performance. In addition, we completed experiments looking at the time course for upregulation and downregulation of SUR1 and TRPM4. The most important findings include 1 SUR1 and TRPM4 begin to appear as early as 2 hours after injury, and are gone by 7 days after injury 2 the dose-response curve for blast intensity vs. biological response is very steep, making it difficult to accurately grade sublethal injuries based on peak overpressure alone 3 the apneac response immediate following blast is an excellent predictor of short-term vestibulomotor performance and of long term cognitive performance, making it a very useful independent variable for grading sublethal injuries when establishing the dose-response.

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  • Anatomy and Physiology
  • Medicine and Medical Research

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