CORE--ANIMAL MODELING AND OUTCOME

我们建议为匹兹堡大学脑创伤研究中心计划项目赠款(PPG)运营一个核心设施，执行与动物建模和结果评估相关的必要程序。这一核心中的设施将由参与本PPG申请的个人提案的下列主要研究人员(PI)使用：1)Steven Graham，M.D.，Ph.D.，Project#1，“BCL-2家族基因在创伤性脑损伤(TBI)中”，2)Steven Dekosky，Project$2，“IL-1 beta，APP代谢和头部损伤中的低温”，3)Patrick Kochanek，M.D.，Project#3，“iNOS and TBI”，4)Edward Dixon，博士，Project#4“TBI的多巴胺机制，和5)罗伯特·克拉克，医学博士，项目#5“脑损伤后的PARS激活。”核心设施将满足以下具体目标：1)为PPG内所有拟议的小鼠和大鼠实验操作提供一个集中的手术和麻醉设施，2)为PPG(受控皮质影响[CI]模型和CCI二次损伤模型)中的小鼠和大鼠的所有研究提供统一的损伤，并通过执行质量控制分析确保一致性，3)为PPG内的功能结果参数(运动和认知)的标准化评估提供中央设施，4)为PPG内的组织结果参数(挫伤体积和海马神经元计数)的标准化评估提供中央设施，5)促进PPG内的PI之间的交互，并促进与匹兹堡核磁共振生物医学研究中心(卡内基梅隆大学)的合作研究人员的交互，以及6)为PPG中使用该疗法的所有研究提供标准化的低温方案。这些特定目标的成功执行将为调查人员提供最佳的资源利用，包括1)技术人员时间、2)实验室空间、3)设备、4)用品、5)动物和6)磁共振成像时间。同时，将确保在小鼠和大鼠身上进行的所有研究的质量控制，并将为PPG内的PI之间的相互作用提供一个结构化的环境。

We propose to operate a core facility that performs the necessary procedures related to Animal Modeling and Outcome Assessment for the University of Pittsburgh Brain Trauma Research Center program project grant (PPG). The facilities in this core will be used by the following principal investigators (PIs) involved in the individual proposals in this PPG application: 1) Steven Graham, M.D., Ph.D., Project #1, "bcl-2 family genes in traumatic brain injury (TBI)", 2) Steven Dekosky., Project $2, "IL-1beta, APP metabolism and hypothermia in head injury", 3) Patrick Kochanek, M.D., Project #3, "iNOS and TBI", 4) Edward Dixon, Ph.D., Project #4 "Dopaminergic mechanisms of TBI," and 5) Robert Clark, M.D., Project #5 "PARS activation after TBI." The core facility will address the following Specific Aims 1) To provide a centralized facility for surgery and anesthesia for all of the proposed experimental manipulations of mice and rats within the PPG, 2) To provide uniform injury for all studies in mice and rats in the PPG (controlled cortical impact [CI] model, and CCI model with secondary insult) and ensure consistency by performing quality control analysis, 3) To provide a centralized facility for the standardized assessment of functional outcome parameters (motor and cognitive) within the PPG, 4) To provide a centralized facility for the standardized assessment of histological outcome parameters (contusion volume and hippocampal neuron counting) within the PPG, 5) To facilitate interaction between the PIs within the PPG, and facilitate interaction with collaborating investigators at the Pittsburgh NMR Center for Biomedical Research (Carnegie Mellon University), and 6) To provide a standardized hypothermia regimen for all studies using this therapy in rats in the PPG. The successful execution of these specific aims will provide for optimal resource utilization by the investigators include the use of 1) technician time, 2) laboratory space, 3) equipment, 4) supplies, 5) animals, and 6) Magnetic Resonance Imaging time. At the same time, quality control will be ensured for all of the studies in mice and rats, and a structured environment for interaction between the PIs within the PPG will be provided.