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

基本信息

批准号：
7172945
负责人：
RICHARD Daniel EGLETON
金额：
$ 7.63万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-04-01 至 2007-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7172945
关键词：
ATP phosphohydrolase Acidosis Actins Active Sites Acute Advanced Glycosylation End Products Affect African American Albumins Aminopeptidase Animal Model Animals Antibodies Apical Arizona Astrocytes Binding Biological Assay Blood Blood - brain barrier anatomy Blood Vessels Blood flow Blurred vision Body Weight decreased Brain Brain Drains Brain Edema Brain hemorrhage Brain region Brush Border Carboxypeptidase Cardiovascular Diseases Cardiovascular system Carrier Proteins Cell membrane Cerebrovascular Disorders Cerebrum Cessation of life Characteristics Choroid Chronic Clinical Communities Complement component C1s Condition Confocal Microscopy Cytoskeletal Proteins Development Diabetes Mellitus Diabetic Angiopathies Diffusion Discontinuous Capillary Disease Dyslipidemias Economics Edema Elderly Electrical Resistance Endopeptidases Endothelial Cells Endothelium Environment Enzymes Ependyma Epidemiologic Studies Epithelial Epithelial Cells Event Extracellular Fluid Fatigue Fenestrated Capillary Frequencies Functional disorder General Population Glucose Goals Health Hemoglobin Hispanics Homeostasis Hyperglycemia Hypertension Immunoprecipitation In Situ Infarction Inflammatory Injection of therapeutic agent Injury Insulin Insulin Resistance Insulin-Dependent Diabetes Mellitus Ion Transport Ions Ischemic Stroke Labyrinth fenestration Lactic acid Lateral Lead Limb structure Link Liquid substance Localized Location Lymphatic System Magnetic Resonance Imaging Maintenance Measures Mechanics Membrane Metabolic Metabolic Diseases Metabolic syndrome Mexican Americans Middle Cerebral Artery Occlusion Modeling Molecular Molecular Weight Morbidity - disease rate Muscle NF-kappa B Na(+)-K(+)-Exchanging ATPase Native Americans Nature Neuraxis Neurons Non-Insulin-Dependent Diabetes Mellitus Numbers Numbness Organ Osmolalities Outcome Patient Admission Patients Peptide Hydrolases Peptides Perfusion Peripheral Permeability Phenotype Phosphoric Monoester Hydrolases Phosphorylation Phosphotransferases Plasma Play Post-Translational Protein Processing Principal Investigator Probability Production Protein Isoforms Protein Kinase C Proteins Pump Radioisotopes Range Rattus Reaction Reactive Oxygen Species Recovery Reporting Retina Risk Risk Factors Role Site Staining method Stains Streptozocin Stress Stroke Structure Structure of choroid plexus Sucrose System Testing Thirst Tight Junctions Time Tissues Urination Vascular Diseases Ventricular Water Week Western Blotting Wound Healing X-Ray Computed Tomography anaerobic glycolysis base blood cerebrospinal fluid barrier blood glucose regulation cell type cost diabetic diabetic rat fighting foot glycosylation kidney epithelial cell lead ion macrophage male mimetics mortality non-diabetic numb protein occludin prevent prognostic programs receptor for advanced glycation endproducts size symporter transcription factor uptake

项目摘要

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经济产生重大影响的疾病，估计每年造成 980 亿美元的损失。它对原住民/西班牙裔和非裔美国人社区的影响尤其大。糖尿病是由于无法产生或正确使用胰岛素而引起的，导致高血糖。糖尿病患者的主要健康问题是心血管疾病，尤其是中风，糖尿病患者中风的概率和死亡率大约高出 3 倍。中风进展和损伤的主要因素之一是脑水肿的形成。中风期间的脑水肿与大量离子流入大脑导致水积聚有关。在正常情况下，进入大脑的离子转运受到血液中枢神经系统屏障（BCNSB）的紧密连接和离子转运蛋白的相互作用的严格控制。据报道，在糖尿病中，许多器官出现离子转运功能障碍。在中风动物模型中，与非糖尿病患者相比，糖尿病患者的梗塞面积和水肿均增加。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会发生改变，导致维持离子稳态的能力降低。在中风期间，这会导致更多的离子流入，导致更严重的水肿形成，从而造成更大的损伤。我们将通过研究糖尿病对对照动物和糖尿病动物中 BCNSB 离子转运蛋白以及紧密连接表达和功能的影响来检验这一假设。我们的最终目标是更好地了解糖尿病中风损伤的机制，这有望带来更好的治疗范例