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Project 2- Correlating microglial activation with blood brain barrier integrity and neurocognitive performance

项目 2 - 将小胶质细胞激活与血脑屏障完整性和神经认知功能相关联

基本信息

批准号：
10214514
负责人：
MEGGAN MACKAY
金额：
$ 84.32万
依托单位：
FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-08-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10214514
关键词：
Adult Affect Anatomy Antibodies Antibody titer measurement Area Assessment tool Benzodiazepine Receptor Blood Blood - brain barrier anatomy Brain Brain imaging Brain region Chronic Clinical Cognition Cognitive Cognitive deficits Communities DNA receptor Data Descriptor Development Diagnostic Diffusion Magnetic Resonance Imaging Disease Disease Marker Exhibits Exposure to Fc Receptor Functional Magnetic Resonance Imaging Funding Gadolinium Hippocampus (Brain)Human Image Imaging Device Impaired cognition Impairment Individual Inflammatory Investigation Ionizing radiation Ligand Binding Logistics Long-Term Effects Lupus Magnetic Resonance Magnetic Resonance Imaging Measurement Measures Mediating Metabolic Metabolism Methods Microglia Molecular Multimodal Imaging Mus N-Methyl-D-Aspartate Receptors Neurocognitive Pathogenicity Pathologic Pathway interactions Patients Performance Peripheral Positron-Emission Tomography Process Proxy Psychometrics Radiation Reporting Reproducibility Research Design Rest Role Scanning Serology Serum Spin Labels Structure Synapses Systemic Lupus Erythematosus Testing Therapeutic Time Tracer base blood-brain barrier permeabilization brain abnormalities brain dysfunction cognitive function cognitive testing contrast enhanced disabling disease fetal fluorodeoxyglucose positron emission tomography healthy volunteer imaging approach imaging biomarker imaging modality imaging study improved in vivo individual patient insight instrumentation intravenous injection longitudinal design mouse model multimodality neuroinflammation neuron loss neurotoxic neurotoxicity neurotransmission non-invasive imaging novel radiotracer response spatial memory synaptic function synaptic pruning targeted biomarker treatment strategy uptake white matter white matter change

项目摘要

Project: 2 Summary/Abstract Project 2 continues our focus on brain imaging studies in human SLE to investigate mechanisms of cognitive dysfunction in patients with this disorder. The proposed study leverages the information gained in the last funding cycle: the presence of consistent elevations in resting metabolic activity (a proxy for local synaptic function) in the hippocampus of SLE patients, which correlated with anti DNA receptor antibody (DNRAb) titers and with performance on cognitive test battery. In the next funding cycle, we plan to use multimodal PET and MRI imaging tools to determine the mechanistic basis for cognitive dysfunction in this disorder. New experimental evidence from Project 1 implicates microglial (MG) activation in the hippocampal neurotoxic response to DNRAb. We will therefore use [11C]-PBR28 PET to assess this phenomenon in SLE patients compared to healthy volunteer subjects. To this end, radiotracer uptake will be quantified in the hippocampus and other metabolically active SLE-related brain regions. Using a longitudinal design, we will evaluate regional MG activation over a two-year period, and determine how these changes relate to concurrent assessments of cognitive functioning, DNRAb titers, and resting metabolic activity measured in the same subjects. Likewise, we will use a quantitative MRI approach to evaluate BBB permeability in the hippocampus and in the other SLE-related brain regions. Changes in this measure will similarly be compared with concurrent serological and cognitive assessments, as well as with the other imaging descriptors of the underlying disease process. The broad applicability of this approach may be limited, however, by the invasiveness of some of the imaging methods. To make these assessments more clinically accessible, we will lastly explore the use of newer non- invasive imaging tools as alternative disease markers. In summary, the multimodal imaging approach in Project 2 will provide objective metrics for the assessment of new treatment strategies for SLE-CI.

项目编号：2摘要/摘要