MORPHOLOGICAL ANALYSES OF NEURAL AND PARANEURAL GRAFTS

神经和神经旁移植物的形态分析

• 批准号: 3923479
• 负责人: JOHN T HANSEN
• 金额: --
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3923479
• 关键词: Ceboidea; Parkinson's disease; adrenal medulla; basal ganglia; blood brain barrier; cell differentiation; cell growth regulation; chromaffin cells; disease /disorder model; early embryonic stage; electron microscopy; graft versus host disease; high performance liquid chromatography; histochemistry /cytochemistry; immunochemistry; laboratory rat; nervous system transplantation; neurogenesis; neurons; spinal cord; sympathetic nervous system

The specific aim of this project is to identify, characterize, and determine the potential for use of alternative sources of donor tissue for transplantation in animal models of Parkinson's disease. Because of the ethical, moral, and legal questions surrounding the use of fetal tissues as potential grafts, alternate sources of donor tissue need to be found which will ameliorate the motor deficits caused by Parkinson's disease. This specific aim will be addressed in light of two working hypotheses: (a) Neural crest derivatives belonging to the sympathoadrenal lineage possess inherent phenotypic characteristics which suggest they would be excellent candidates for neural transplantation; and (b) The adult adrenergic derivatives of this lineage, when transplanted into the denervated striatum, will significantly reverse the functional deficits, survive in the host, and continue to elaborate catecholamines. These working hypotheses will be tested both in vitro and in vivo using the three adult adrenergic derivatives of the lineage: (a) principal neurons; (b) adrenal chromaffin cells; and (c) SIF, or glomus cells. The growth and phenotypic differentiation of these cells will be studied using neurochemistry (HPLC), immunohistochemistry, histofluorescence, and scanning and transmission electron microscopy. For my in vivo experiments, the 6-OHDA treated rat model of Parkinson's disease will be used to study the survival and differentiation of implanted cells and tissue fragments of the sympathoadrenal lineage. Moreover, the host response to transplants will be studied ultrastructurally with respect to reactive gliosis, macrophage activity, and the integrity of the blood-brain barrier. In conjunction with these rodent experiments, I will collaborate with those projects using the MPTP primate model of Parkinson's disease by providing EM analysis of their transplants. The behavioral, neurochemical, and morphological results of the rodent studies will be compared with those obtained from the primate experiments. The long-term goals of this work will be to determine the potential of sympathoadrenal cells for use as transplants in humans. The fundamental knowledge gained from these transplantation studies may provide practical clinical approaches to promote recovery from Parkinson's disease and other CNS debilitating diseases such as Alzheimer's disease, Huntington's chorea and CNS trauma.

该项目的具体目标是识别、表征和 确定使用替代捐助来源的潜力 用于帕金森病动物模型移植的组织。 由于围绕着伦理、道德和法律问题 使用胎儿组织作为潜在的移植物、替代供体来源 需要找到可以改善运动缺陷的组织 由帕金森病引起。 这一具体目标将得到解决 根据两个工作假设：(a) 神经嵴导数 属于交感肾上腺谱系，具有固有的 表型特征表明它们会很优秀 神经移植候选人； (b) 成人肾上腺素能 当移植到去神经系统中时，该谱系的衍生物 纹状体，将显着逆转功能缺陷，生存 在宿主，继续细化儿茶酚胺。 这些 工作假设将在体外和体内进行测试 该谱系的三种成人肾上腺素能衍生物： (a) 主要成分 神经元； (b) 肾上腺嗜铬细胞； (c) SIF，或血管球细胞。 这些细胞的生长和表型分化将 使用神经化学（HPLC）、免疫组织化学进行研究， 组织荧光、扫描和透射电子 显微镜。 在我的体内实验中，6-OHDA 处理的大鼠 帕金森病模型将用于研究生存和 植入细胞和组织碎片的分化 交感肾上腺谱系。 另外，楼主回复 移植物将进行超微结构研究 反应性神经胶质增生、巨噬细胞活性和神经胶质细胞的完整性 血脑屏障。 与这些啮齿动物一起 实验，我将使用这些项目与 通过提供 EM 建立帕金森病的 MPTP 灵长类动物模型 分析他们的移植物。 行为、神经化学和 啮齿动物研究的形态学结果将与 那些从灵长类动物实验中获得的。 长期来看 这项工作的目标是确定 交感肾上腺细胞用作人类移植物。 这 从这些移植研究中获得的基础知识 可以提供促进康复的实用临床方法 帕金森病和其他中枢神经系统衰弱性疾病，例如 如阿尔茨海默病、亨廷顿舞蹈病和中枢神经系统创伤。