In Vivo Model and Histology Core

体内模型和组织学核心

• 批准号: 10556414
• 负责人: Gehua Zhen
• 金额: $ 49.36万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-15 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10556414
• 关键词: 3-Dimensional; Aging; Animal Model; Animals; Behavior; Biomechanics; Blinded; Cartilage; Categories; Charge; Classification; Clinical; Communication; Continuing Education; Data; Data Analyses; Degenerative Disorder; Degenerative polyarthritis; Ensure; Environment; Equipment; Evaluation; Fast Green; Functional disorder; Goals; Grouping; Histologic; Histology; Histopathologic Grade; Histopathology; Human Resources; Hyperalgesia; Image Analysis; Individual; International; Intervertebral disc structure; Investigation; Joints; Knee joint; Laboratories; Laboratory Personnel; Measurement; Mechanics; Medial meniscus structure; Methods; Microsurgery; Modeling; Morphology; Operative Surgical Procedures; Organism; Outcome; Pain; Pathogenicity; Pathologic; Persons; Procedures; Program Research Project Grants; Protocols documentation; Reproducibility; Reproducibility of Results; Research; Research Personnel; Resources; Running; Scanning; Services; Severities; Skeleton; Societies; Specialist; Spinal; Spinal Ganglia; Stains; Standardization; Symptoms; System; Testing; Therapeutic; Time; Tissues; Training; Translating; Variant; Vascularization; Vertebral column; age related; articular cartilage; behavior test; bone; conditioned place preference; cost; design; drug candidate; experience; experimental study; gait examination; in vivo; in vivo Model; in vivo imaging; insight; joint destruction; lumbar vertebra bone structure; member; microCT; mouse model; multidisciplinary; operation; physically handicapped; pre-clinical; programs; skeletal; subchondral bone; tissue preparation; tomography

PROJECT SUMMARY The purpose of the in vivo Animal model & histology core is to consolidate key personnel and equipment to provide a centralized facility that will enhance collaborative and multidisciplinary investigations into multiple mechanisms in age related skeletal degenerative disease. Core B will serve as a center to realize an optimized and reasonable utilization and allocation of experimental and human resources. Employing skillful personnel to conduct the common procedures in a standardized manner is not only a cost- and time-efficient strategy but also can maximally reduce the potential for bias and increase the scientific rigor. Ranging from tissue histological analysis to functional behavior test, Core B will facilitate the investigation of age related skeletal degenerative diseases from four aspects: 1. Animal models and microsurgeries. The proposed surgical animal models: destabilization of the medial meniscus (DMM), lumbar spine instability (LSI), dorsal root ganglion (DRG) exposure for in vivo imaging will be conducted in the Core B. Our core will set up a team with members who have extensive experience in conducting complicated microsurgeries in small animals. 2. Histological grading. Core B will perform histological grading based on the Safranin O/fast green and H&E staining. The osteoarthritis research society international (OARSI) scoring system will be applied to assess the joint degenerative status while the grading method for classification of age-related changes in lumbar intervertebral discs will be used to determine the degenerative status of lumbar discs. 3. Micro-CT analysis. Micro-CT measurements will be done in excised lumbar vertebrae and knee joints to determine the individual volumetric, densitometric and 3- dimensional microarchitecture of subchondral bone or endplate. These parameters are essential for investigating the biomechanical impact of subchondral bone on articular cartilage or endplate on intra-vertebral discs. 4: Behavior test. To better translate the preclinical results into clinical settings, behavior test will be applied to all the 4 projects within this PPG program. Core B will perform gait analysis, Von Frey test, Mechanical hyperalgesia and cold sensitivity test for individual projects. To reduce the variability that potentially generated because of the changes of environment, the different handling of animals, Core B will designate well trained personnel in charging of the animal behavioral tests and equipment/facility management. 5. Training. The Core will train and maintain the continuing education of a key laboratory person from each project to help perform the routine histological, behavior and micro-CT analysis.

项目概要 体内动物模型和组织学核心的目的是整合关键人员和设备， 提供一个集中设施，加强对多个领域的协作和多学科调查 年龄相关性骨骼退行性疾病的机制。以Core B为中心，实现优化 合理利用和配置实验资源和人力资源。雇用熟练的人员 以标准化方式执行通用程序不仅是一种节省成本和时间的策略，而且 可以最大程度地减少潜在的偏见并提高科学严谨性。从组织组织学 功能行为测试分析，Core B将有助于年龄相关骨骼退行性病变的研究 从四个方面研究疾病： 1.动物模型和显微外科。拟议的手术动物模型： 内侧半月板不稳定 (DMM)、腰椎不稳定 (LSI)、背根神经节 (DRG) 活体成像曝光将在Core B进行。我们的Core将成立一个团队，成员包括 在对小动物进行复杂的显微手术方面拥有丰富的经验。 2.组织学分级。 Core B 将根据番红 O/固绿和 H&E 染色进行组织学分级。骨关节炎 将应用国际研究协会（OARSI）评分系统评估关节退化状况 而腰椎间盘与年龄相关变化的分级方法将用于 确定腰椎间盘退变状态。 3.显微CT分析。将进行显微 CT 测量 在切除的腰椎和膝关节中测定个体的体积、密度和 3- 软骨下骨或终板的三维微结构。这些参数对于调查至关重要 软骨下骨对椎间盘上的关节软骨或终板的生物力学影响。 4： 行为测试。为了更好地将临床前结果转化为临床环境，行为测试将应用于所有 该 PPG 计划中的 4 个项目。核心 B 将执行步态分析、Von Frey 测试、机械痛觉过敏 以及个别项目的冷敏感性测试。为了减少由于以下原因可能产生的变异性 环境的变化，对动物的不同处理，Core B 将指定训练有素的人员 负责动物行为测试和设备/设施管理。 5. 培训。核心人员将进行培训并 维持每个项目的关键实验室人员的继续教育，以帮助执行日常工作 组织学、行为和显微 CT 分析。