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Glyburide - Novel Prophylaxis and Effective Treatment for Traumatic Brain Injury

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Annual rept. 7 Jul 2009-6 Jul 2010

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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 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.

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  • Medicine and Medical Research

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