Head injury is an important clinical problem which is poorly understood and often unsuccessfully treated. Rodent models of head injury (such as the controlled cortical contusion model) have been developed that produce many of the features of human head injury. Using a given model, the importance of standardization methodologies in the investigation of the pathobiology and treatment of experimental traumatic brain injury is well recognized. We propose to operate a CORE facility that addresses the following SPECIFIC AIMS: 1) To provide a centralized facility for surgery and anesthesia for all of the proposed experimental manipulations of rats within this program project grant (PPG), 2) To provide uniform traumatic injury for all of the rat studies in the PPG (controlled cortical contusion model), and to ensure consistency of the insult severity by performing monthly quality control analysis, 3) To provide a centralized facility for the standardized assessment of both traumatic lesion volume and percent brain water (%BW) for all experiments within the PPG, 4) To facility the interaction between each of the PIs in the PPG (University of Pittsburgh Head Injury Research Center) and the collaborating investigators at the Pittsburgh NMR Center for Biomedical Research (Carnegie Mellon University), and 5) To provide a standardized hypothermia treatment regimen for all studies utilizing this therapeutic intervention in rats in the PPG. This CORE facility will be used by the following principal investigators involved in the individual proposals of this PPG: 1) Alan Palmer, Ph.d., """"""""Excitatoxicity and free radical formation in brain trauma,' 2) Steven DeKosky, M.D., """"""""Cytokines and neurotropic factors in traumatic brain injury,"""""""" and 3) Patrick Kochanek, M.D., """"""""Neutrophils and the acute inflammatory response to traumatic brain injury."""""""" To achieve these Specific Aims, a CORE laboratory has been established and specific protocols have been developed for the anesthesia and surgery involved in producing trauma in rats by controlled cortical contusion. Detailed protocols have also been developed for evaluation of traumatic lesion volume, and %BW using T2-weighted and proton density magnetic resonance imaging, respectively. In addition, a standardization hypothermia treatment regimen has been developed. Many of these protocols were used for the generation of the preliminary reports in this PPG. The successful execution of these Specific Aims will provide for optimal resource utilization by the investigators, including use of 1) technician time, 2) laboratory space, 3) equipment, 4) supplies, 5) rats, and 6) MRI time. At the same time, uniformity of the choice of the model among the investigators and quality control will also be ensured for all rat studies within the PPG. Finally, this CORE will facilitate both the interpretation of the findings of each PI and the interaction between PIs within the PPG. It will similarly facilitate comparison of our results with those from other laboratories nationally.
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