Diabetes and Stroke: A Role for the Blood CNS Barriers

糖尿病和中风：血液中枢神经系统屏障的作用

• 批准号: 6780335
• 负责人: RICHARD Daniel EGLETON
• 金额: $ 28.95万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6780335
• 关键词: blood brain barrier; brain edema; central nervous system; cerebrospinal fluid; confocal scanning microscopy; diabetes mellitus; disease /disorder model; edema; gene expression; glucose; hyperglycemia; immunoprecipitation; insulin; ion transport; laboratory rat; membrane transport proteins; pathologic process; posttranslational modifications; stroke; tight junctions; western blottings

DESCRIPTION (provided by applicant): Diabetes is a disease that has a major economic impact on the US, with an estimated cost of $ 98 billion per year. It is of particularly high impact in the Native / Hispanic and African American communities. Diabetes is caused by an inability to produce or properly use insulin, resulting in hyperglycemia. The major health concern for diabetics is cardiovascular disease, particularly stroke, with diabetics having approximately 3 times higher probability of and mortality from stroke. One of the major factors in stroke progression and damage is brain edema formation. Brain edema during stroke has been linked to a large influx of ions into the brain, leading to water accumulation. Under normal conditions ion transport into the brain is tightly controlled by an interaction of the tight junctions and ion transporter of the blood central nervous system barriers (BCNSB). In diabetes, ion transport dysfunction has been reported in a number of organs. In animal models of stroke, infarct size and edema are increased in diabetics compared to non-diabetics. It is our hypothesis that during diabetes, both the tight junctions and ion transporters of the BCSNB are altered, resulting in a reduced ability to maintain ion homeostasis. During stroke this results in a larger influx of ions, leading to a more significant edema formation and thus more damage. We will test this hypothesis by investigating the effect of diabetes on BCNSB ion transporter and tight junction expression and function in control and diabetic animals. Our eventual goal is to gain a better understanding on the mechanisms involved in diabetic stroke damage, which will hopefully lead to better treatment paradigms

描述（由申请人提供）：糖尿病是一种对美国产生重大经济影响的疾病，估计每年成本为980亿美元。它在本地 /西班牙裔和非裔美国人社区中的影响尤其高。糖尿病是由于无法产生或适当使用胰岛素而导致高血糖引起的。糖尿病患者的主要健康问题是心血管疾病，尤其是中风，糖尿病患者的中风可能性高约3倍。 中风进展和损害的主要因素之一是脑水肿的形成。中风期间的大脑水肿与大量离子涌入大脑有关，从而导致水积聚。在正常情况下，离子转运到大脑的运输受到血液中枢神经系统屏障（BCNSB）的紧密连接蛋白和离子转运蛋白的相互作用的紧密控制。 在糖尿病中，已经报道了许多器官的离子运输功能障碍。在中风的动物模型中，与非糖尿病患者相比，糖尿病患者的梗塞大小和水肿增加。我们的假设是，在糖尿病期间，BCSNB的紧密连接和离子转运蛋白都在改变，从而降低了维持离子稳态的能力。在中风期间，这会导致离子大量涌入，从而导致更明显的水肿形成，从而更大的损害。 我们将通过研究糖尿病对BCNSB离子转运蛋白以及对照和糖尿病动物的紧密连接表达以及功能的影响来检验这一假设。我们最终的目标是更好地了解糖尿病性中风损害所涉及的机制，这将有望导致更好的治疗范例