The protective effect of Emmprin inhibition in acute cerebrovascular disease.

Emmprin 抑制对急性脑血管疾病的保护作用。

• 批准号: 8492535
• 负责人: Louise D. McCullough
• 金额: $ 23.1万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-02-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8492535
• 关键词: Acute; Age-Months; Animals; Antibodies; Area; Astrocytes; Basement membrane; Behavioral; Biological; Biologically Based Therapy; Blocking Antibodies; Blood - brain barrier anatomy; Blood Vessels; Brain; Brain Injuries; Brain Ischemia; Cell Adhesion Molecules; Cells; Cerebrovascular Disorders; Chronic; Clinical; Cyclophilins; Disease; Dose; Edema; Endothelial Cells; Event; Experimental Autoimmune Encephalomyelitis; Experimental Models; Extracellular Matrix; Extravasation; Family; Free Radicals; Funding; Gelatinase B; Goals; Hour; Immune; Immune response; Immune system; Immunosuppression; Infarction; Infiltration; Inflammation; Inflammatory; Injury; Investigation; Ischemia; Ischemic Stroke; Lead; Leukocyte Trafficking; Leukocytes; Matrix Metalloproteinases; Mechanics; Mediating; Membrane Glycoproteins; Middle Cerebral Artery Occlusion; Modeling; Multiple Sclerosis; Mus; Neuroglia; Neurologic; Neurons; Outcome; Patients; Peptide Hydrolases; Peripheral; Permeability; Phase; Play; Process; Production; Recovery; Recovery of Function; Regulation; Reperfusion Therapy; Role; Secondary to; Series; Severity of illness; Staging; Stimulus; Stroke; Systemic disease; Therapeutic Intervention; Time; Vascular remodeling; Vasodilation; Work; Zinc; aged; angiogenesis; base; cell type; cohort; cytokine; disability; expectation; functional outcomes; functional restoration; in vivo; male; migration; monocyte; neutrophil; novel; post stroke; protective effect; public health relevance; theories; therapeutic development; trafficking

DESCRIPTION (provided by applicant): Ischemic stroke is now the most frequent cause of persistent neurologic disability in the US. Despite considerable effort there are no therapies that can reduce injury or restore function once a stroke occurs. Over the past several years, our view of stroke as a "neuronal disease" has been transformed into the concept of stroke as a "neurovascular" disease, and more recently into the novel theory that stroke is truly a "systemic" disease in which peripheral inflammatory processes play a fundamental role. Secondary injury from the infiltration of peripheral immune cells is increasingly recognized as a major contributor to brain injury, edema and hemorrhagic transformation. These cells require proteases to transmigrate into the brain, a process mediated primarily by activation of matrix metalloproteinases (MMPs). Extracellular Matrix Metalloproteinase Inducer (EMMPRIN; CD 147) is a 58-kDa cell surface glycoprotein that regulates leukocyte trafficking into the brain. The proposed work will examine regulation of CD147 after stroke and determine if a function blocking antibody can reduce injury or blood brain barrier (BBB) breakdown. These effects will be confirmed in aged animals (Aim 1) and with chronic functional assessments (Aim 2). This preliminary work will set the stage for an investigation of the potential for other biologically based therapies to treat stroke. These exploratory studies will hopefully identify new biological targets for therapeutic intervention for patients with stroke.

描述（由申请人提供）：缺血性中风现在是美国最常见的持续性神经功能障碍的原因。尽管付出了巨大的努力，但没有任何疗法