Striatal Immune Response In Aged Rats

老年大鼠纹状体免疫反应

• 批准号: 7017028
• 负责人: SUSAN O MCGUIRE
• 金额: $ 5.95万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-01 至 2008-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7017028
• 关键词: Parkinson' s disease; age difference; aging; angiosperms; animal old age; antiinflammatory agents; antioxidants; apoptosis; brain injury; cell transplantation; dietary supplements; dopamine; embryo /fetus tissue transplantation; immune response; immunocytochemistry; immunomodulators; juvenile animal; laboratory rat; nervous system transplantation; neurogenesis; neuroimmunomodulation; neurons; neurotrophic factors; nonhuman therapy evaluation; nutrition related tag; oxidative stress; plant extracts; substantia nigra; western blottings

DESCRIPTION (provided by applicant): The exact mechanisms underlying poor cell survival and graft dysfunction in neural repair paradigms for Parkinson's disease are unknown. However, transplantation-induced oxidative stress and host immune response have been hypothesized as contributing factors as dopamine (DA) neurons are exquisitely sensitive to oxidative damage and inflammation. Therefore, aging-related increases in oxidant stress, decreases in antioxidant protection and production of trophic factors in addition to a suboptimal immune function may provide a more hostile transplant environment, resulting in the decreased efficacy or lack of therapeutic benefit observed in aged individuals receiving transplanted DA neurons. Although multiple studies have attempted to improve overall cell survival by pre-treating the cell transplant material with various anti-apoptotic or antioxidant compounds, these approaches do not address the issue of further decreased cell survival and efficacy in aged recipients. We have recently shown that dietary supplementation with phytochemicals significantly improves the survival of transplanted embryonic DA neurons in both young and old rats. Additionally, functional efficacy of a suboptimal graft was achieved in young animals receiving blueberry extract (BBE). BBE is a fruit extract with immunomodulatory, antioxidant, and anti-inflammatory properties that previously has been shown to restore striatal associated motor function in aged rats. The neurotrophic/immunomodulatory mechanisms that underlie these observations have yet to be explored. The current application proposes to examine the effect of dietary BBE on injury-related aspects of neural transplantation paradigms in young versus old rats. This design allows differentiation of diet induced changes in the mesostriatal system from age-related changes in response to the penetrating wound used to place embryonic cells into the brain. We hypothesize that dietary supplementation with BBE will decrease immune and inflammatory responses and improve trophic factor production in response to a penetrating striatal wound in young and old rats. These studies will provide support for the potential of dietary phytochemicals to provide an efficacious, easily administered and well tolerated therapy that can be used to improve graft survival and function in cell replacement therapies, whether they utilize embryonic tissue or stem cells.

描述（由申请人提供）：帕金森氏病神经修复范式中细胞存活不良和移植功能障碍的确切机制尚不清楚。然而，移植引起的氧化应激和宿主免疫反应已被认为是促成因素，因为多巴胺（DA）神经元对氧化损伤和炎症非常敏感。因此，与衰老相关的氧化应激的增加，抗氧化剂保护的降低和营养因子的产生外，除了次优的免疫功能外，还可以提供更敌对的移植环境，从而导致疗效或缺乏治疗益处的降低，从而在接受移植DA神经元的年龄个体中观察到的治疗益处。尽管多项研究试图通过使用各种抗凋亡或抗氧化剂化合物来预处细胞移植材料来改善总体细胞存活，但这些方法并不能解决老年接受者进一步降低细胞存活和功效的问题。我们最近表明，补充植物化学物质的饮食可显着提高年轻大鼠和老鼠中移植的胚胎DA神经元的存活。此外，在接受蓝莓提取物（BBE）的年轻动物中，次优移植物的功能功效。 BBE是一种具有免疫调节，抗氧化剂和抗炎特性的水果提取物，以前已被证明可以恢复老年大鼠的纹状体相关运动功能。这些观察结果尚未探讨的神经营养/免疫调节机制。当前的应用建议检查饮食BBE对年轻大鼠和老鼠的神经移植范例与损伤相关的方面的影响。这种设计允许饮食诱导的介质系统变化与年龄相关的变化，以应对与年龄相关的变化，以响应用于将胚胎细胞放入大脑的穿透伤。我们假设补充饮食会减少免疫和炎症反应，并改善对年轻大鼠穿透性纹状体伤口的反应，从而改善营养因子的产生。这些研究将为饮食中的植物化学物质的潜力提供支持，以提供有效，易于施用且耐受性良好的疗法，可用于改善移植物存活率和在细胞替代疗法中的功能，无论它们是利用胚胎组织还是干细胞。