Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE (DD-MM-YYYY)2. REPORT TYPE 3. DATES COVERED (From -To) 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail:5f. WORK UNIT NUMBER 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. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTThe 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: (i) SUR1 and TRPM4 begin to appear as early as 2 hours after injury, and are gone by 7 days after injury; (ii) 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; (iii) 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.blast-TBI, sulfonylurea receptor The ove...
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