MORPHOLOGICAL ANALYSES OF NEURAL AND PARANEURAL GRAFTS

神经和神经旁移植物的形态分析

• 批准号: 3882482
• 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/3882482
• 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 确定使用其他捐助来源的可能性 帕金森病的动物模型中移植的组织。 由于围绕着这一问题的伦理、道德和法律的问题， 使用胎儿组织作为潜在的移植物，供体的替代来源 需要找到一种组织来改善运动缺陷 帕金森氏症引起的 这一具体目标将在 根据两个工作假设：（a）神经嵴衍生物 属于交感肾上腺谱系， 表型特征表明他们将是优秀的 （B）成年肾上腺素能受体 这种谱系的衍生物，当移植到失神经的 纹状体，将显着扭转功能缺陷，生存 在主机，并继续阐述儿茶酚胺。 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）主要的 神经元;（B）肾上腺嗜铬细胞;和（c）SIF，或血管球细胞。 这些细胞的生长和表型分化将是 使用神经化学（HPLC），免疫组织化学， 组织荧光、扫描和透射电子 显微镜 对于我的体内实验，6-OHDA治疗的大鼠 帕金森病模型将用于研究生存率和 移植的细胞和组织碎片的分化 交感肾上腺谱系 此外，主机响应 将从超微结构上研究移植物， 反应性神经胶质增生，巨噬细胞活性，和完整的 血脑屏障 与这些啮齿动物一起 实验，我将与这些项目合作，使用 通过提供EM的MPTP灵长类帕金森病模型 分析他们的移植。 行为神经化学 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 这项工作的目标将是确定 交感肾上腺细胞用于人体移植。 的 从这些移植研究中获得的基本知识 可以提供实用的临床方法来促进康复 帕金森氏病和其他中枢神经系统衰弱性疾病， 阿尔茨海默氏病、亨廷顿舞蹈病和中枢神经系统损伤。