Investigating Neurological Injury Patterns in the Minipig Following Impact

研究小型猪撞击后的神经损伤模式

• 批准号: 9512048
• 负责人: PAMELA J. VANDEVORD
• 金额: $ 39.37万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9512048
• 关键词: Acute; Address; Adult; Affect; Affective; Amyloid beta-Protein Precursor; Anatomy; Animal Model; Animals; Anxiety; Attention; Behavior; Behavioral; Biological; Biomechanics; Body Size; Brain; Brain region; Clinical; Clinical Treatment; Cognitive; Complex; Development; Devices; Diagnosis; Diffusion Magnetic Resonance Imaging; Experimental Animal Model; FDA approved; Female; Fiber; Functional disorder; Glial Fibrillary Acidic Protein; Goals; Histology; Image; Imaging Techniques; Impaired cognition; Impairment; Inflammation; Inflammatory; Injury; Intervention; Knowledge; Link; Magnetic Resonance Imaging; Measurement; Measures; Mechanics; Memory; Mental Depression; Metabolic; Miniature Swine; Modeling; Modernization; Monitor; Nerve Degeneration; Nervous System Trauma; Neurodegenerative Disorders; Neuroglia; Neurologic; Neurons; Neuroprotective Agents; Outcome; Pathologic; Pattern; Pharmaceutical Preparations; Phase III Clinical Trials; Play; Pre-Clinical Model; Recovery; Research; Role; Rotation; Safety; Severities; Sex Characteristics; Signal Transduction; Societies; Standardization; Techniques; Testing; Time; Translations; Trauma; Traumatic Brain Injury; United States; Variant; axon injury; behavior test; clinically relevant; clinically translatable; cognitive testing; drug discovery; expectation; experimental study; falx cerebri; improved; in vivo; in vivo Model; insight; male; neurofilament; neuroimaging; neuropathology; new therapeutic target; pre-clinical; regional atrophy; response; response to injury; sex; species difference; tool; treatment strategy

Project Summary Traumatic brain injury (TBI) continues to be a serious problem in society with 1.7 million occurrences annually in the United States. Currently there have been no neuroprotective drug trials to survive past Phase III clinical trials. Previous in vivo testing, involves injury models that are not clinically-relevant, do not include biological variability and are typically small animal models. There is a need to study impact-TBI in a gyrencephalic minipig model using a repeatable combined translation and rotation-input injury device. The specific aims of this study are to: 1) Determine the acute behavioral and pathologic effects of two impact-induced TBI severities in minipigs, 2) Determine whether the Göttingen or the Yucatan minipig is the more appropriate large animal model for impact-induced TBI using neuropathological, imaging, and behavioral techniques and to 3) Determine sex influences on acute behavioral and pathologic effects following impact-induced TBI. Complex MR imaging techniques and cognitive/behavioral tests will be used to measure changes compared to pre-injury assessments and longitudinally within the same animal to evaluate possible recovery caused by two impact severities. Histology will define the underlying damage compared to sham animals. Cognitive impairments and MR imaging changes can be related to underlying damage to make a link between noninvasive and invasive measurements. These measures can also help ease translation to clinical tools to improve diagnosis and intervention. Addressing biological variability by evaluating different minipig species and sex differences will help address some of the limitations in current preclinical models. Ultimately, developing a standardized preclinical model that produces clinically-relevant impact TBI in a gyrencephalic animal model will better measure drug safety and efficacy. In addition, a well-characterized model can give insight into new drug targets that were missed by previously used in-vivo models with non-realistic injury conditions.

项目摘要 创伤性脑损伤（TBI）在社会中仍然是一个严重的问题，每年发生170万次发生 在美国。 试验。 可变性，通常是小动物模型。 Minipig模型使用可重复的合并翻译和旋转输入损伤装置。 这项研究是：1）确定两个撞击引起的TBI严重程度的急性行为和病理效应 在Minipigs中，2）确定Göttingen还是Yucatan Minipig是合适的大动物 使用神经疾病的，成像和行为技术的撞击诱导的TBI模型，至3） 确定对撞击引起的TBI后急性行为和病理影响的影响 MR成像技术技术/行为测试将用于测量变更对受伤前的变化 评估和纵向在同一动物中，以评估两种影响可能引起的 与假动物相比，认知障碍和组织学将定义潜在的损害。 MR成像变化可能与潜在的损害有关，以建立无创和侵入性之间的联系 测量。 通过评估不同的微型和性别差异来解决生物 帮助解决当前临床前模型中的一些局限性。 临床上的临床模型在沟道型动物模型中产生与临床相关的影响TBI会更好 衡量药物安全性和功效。 先前使用的具有非现实损伤条件的体内模型错过的目标。