CORE--ANIMAL MODELING AND OUTCOME

我们建议运营一个核心设施，为匹兹堡大学脑外伤研究中心项目拨款（PPG）执行与动物建模和结果评估相关的必要程序。该中心的设施将由以下主要研究人员（pi）使用，这些主要研究人员参与了该PPG申请中的个人提案：1)Steven Graham， M.D, Ph.D.项目#1，“创伤性脑损伤（TBI）中的bcl-2家族基因”，2)Steven Dekosky。3) Patrick Kochanek，医学博士，项目#3，“iNOS与脑损伤”，4)Edward Dixon，博士，项目#4，“脑损伤后多巴胺能机制”，以及5)Robert Clark，医学博士，项目#5，“脑损伤后PARS激活”。核心设施将满足以下具体目标：1)为PPG内小鼠和大鼠的所有拟议实验操作提供集中的手术和麻醉设施；2)为PPG中小鼠和大鼠的所有研究提供统一的损伤（控制性皮质冲击[CI]模型和继发性损伤的CCI模型），并通过执行质量控制分析确保一致性。3)为PPG内功能结果参数（运动和认知）的标准化评估提供集中设施，4)为PPG内组织学结果参数（挫伤量和海马神经元计数）的标准化评估提供集中设施，5)促进PPG内pi之间的相互作用，促进与匹兹堡核磁共振生物医学研究中心（卡耐基梅隆大学）的合作研究人员的互动。6)为所有在PPG中使用该疗法的大鼠研究提供标准化的低温治疗方案。这些具体目标的成功实施将为研究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)供应，5)动物和6)磁共振成像时间的使用。同时，将确保所有小鼠和大鼠研究的质量控制，并提供PPG内pi之间相互作用的结构化环境。

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.