Longitudinal Monitor of Microglia Activation After Stroke with SPION-enhanced MRI

使用 SPION 增强 MRI 纵向监测中风后小胶质细胞激活

• 批准号: 8871417
• 负责人: Yi Yang
• 金额: $ 22.65万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8871417
• 关键词: Alzheimer' s Disease; Amyloid; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Antibodies; Area; Basic Science; Biochemical; Biological Markers; Blood; Blood - brain barrier anatomy; Brain; Brain Injuries; Cells; Cerebral Ischemia; Cerebrum; Clinic; Clinical Research; Comorbidity; Confocal Microscopy; Contrast Media; Data; Detection; Development; Diagnosis; Disease; Enzyme-Linked Immunosorbent Assay; Evaluation; Event; Extravasation; Foundations; Goals; Growth; Growth Factor; Hematoxylin and Eosin Staining Method; Human; Image; Immune; Immunoglobulin G; Immunohistochemistry; Inbred SHR Rats; Infarction; Infiltration; Inflammation; Inflammatory; Inflammatory Response; Intervention; Investigation; Iron; Ischemia; Ischemic Stroke; Knowledge; Label; Lead; Lesion; Life; Location; Longitudinal Studies; MRI Scans; Magnetic Resonance Imaging; Measures; Medicine; Methods; Microglia; Middle Cerebral Artery Occlusion; Mission; Modeling; Molecular; Monitor; Mus; Nerve Degeneration; Patients; Pericytes; Peripheral; Permeability; Phase; Platinum; Play; Process; Proteins; Prussian blue; Public Health; Rattus; Reaction; Recovery; Recovery of Function; Reperfusion Therapy; Research; Rest; Role; Sensitivity and Specificity; Specificity; Staging; Staining method; Stains; Stroke; Techniques; Testing; Tight Junctions; Time; Tissues; Treatment Efficacy; Weight; antibody conjugate; blood perfusion; clinical practice; clinically relevant; cytokine; design; imaging biomarker; imaging modality; improved; in vivo; inflammatory marker; iron oxide; leukocyte activation; macrophage; nanoparticle; nervous system disorder; neuroinflammation; neurological recovery; neurorestoration; novel; novel therapeutics; public health relevance; repaired; research study; response; restoration; stroke recovery; therapeutic target; tissue regeneration; tissue repair

 DESCRIPTION (provided by applicant): Longitudinal monitoring of microglial activation after stroke with SPION-enhanced MRI ABSTRACT: Microglia are the brain-resident macrophages that form the first line of immunological defense in the brain. Emerging evidence indicates that microglial activation and leukocyte infiltration play a major role in the pathogenic cascades of cerebral ischemia: cellular reactions determine the extent of ischemia-induced tissue damage but are also necessary for tissue repair and regeneration during recovery. Despite the existence of a number of prior experimental and clinical studies focusing on activated microglia for the study of neuroinflammation after focal cerebral ischemia, an accurate, efficacious, and non-invasive method for monitoring the functional alteration of microglia during stroke recovery is stil lacking. Our preliminary results suggest that microglial activity is involved in the restoration of the integrity of the blood-brain barrier (BBB) during neurovascular remodeling after stroke at all stages, ranging from the early pro-inflammatory (M1) to the later anti-inflammatory and tissue repair (M2) stages. We propose to test the hypothesis that the functional alteration of microglia shifts from a classical early pro-inflammatory activation to the later expression of growth factors involved in neurovascular remodeling. In this proposal we will focus on applying a novel technique for MRI detection of microglial-targeted, superparamagnetic nanoparticles in rat brain to evaluate the alteration of microglia functional activation during stroke recovery. In this projet, we propose the following two specific aims; AIM1 to monitor the dynamic distribution profile of active microglia in rat ischemic brain with MRI and nanoparticles conjugated with a biomarker to microglia at 7, 14, and 28 days after stroke, and AIM2 to study the molecular and cellular changes during functional alterations of microglia in response to stroke-induced brain injury and recovery with histological and biochemical approaches. This proposal will combine the use of nanoparticles conjugated to an anti-Iba-1 antibody as a marker of microglia with MR imaging to non-invasively monitor the temporal profile of inflammation and microglia functional alteration in the brain after a stroke. Although the use of peripheral and imaging biomarkers have increased the specificity and sensitivity of the in vivo diagnosis of stroke, it would be of great clinical relevance to be able to non-invasively monitor the longitudinal development of inflammation in the brain of stroke subjects. MRI is widely used in medicine and widely available in clinical practice. Thus, an MRI method for imaging the inflammatory response inside the living stroked brain could be widely applied and would open these research areas to a great number of quantitative investigations in vivo where the efficacy of treatments could be determined and compared. This research will provide a novel experimental approach for monitoring the progression and treatment of stroke and other neurodegeneration disorders in support of direct subsequent applications in the clinic. In addition, the successful completion of the proposed studies will enhance our understanding of the functional alteration of microglia and the role of the key inflammatory events in neurovascular remodeling following stroke.

 描述（通过应用程序证明）：用SPION增强MRI的中风后的小胶质细胞激活是Ain居住的巨噬细胞，其中最大的巨噬细胞在大脑中的免疫粒子防御措施中，确定了kikocyte的主要作用。缺血性的组织损伤的程度，但在恢复过程中的组织和遗产也是遗产的。 在各个阶段，在中风后神经血管重塑期间的血液锁骨（BBB）的完整性，从早期的促炎物E后来的抗炎和组织修复（M2）阶段。小胶质细胞从经典的早期促炎激活转移到后来的颗粒因子 在此提案中，我们将重点介绍MRI检测小胶质细胞的MRI检测。在大鼠缺血性大脑中，MRI和纳米颗粒在中风后的7、14和28天具有生物标志物至小胶质细胞，以及AIM2，以研究小胶质细胞的分子和变化在小胶质细胞中，以响应中风诱导的脑损伤，从。中风，能够无创地监测中风受试者的纵向发育，这是一种引人注目的。可以确定和比较的许多治疗方法的研究区域，以监测中风和其他神经退行性疾病的进度和治疗，以支持诊所中的ubb。将增强我们对小胶质细胞的功能变化的理解以及关键事件在中风后神经血管重塑中的作用。