权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Brain Vascular Heterogeneity

脑血管异质性

基本信息

批准号：
10437595
负责人：
CARLOS A PARDO-VILLAMIZAR
金额：
$ 23.09万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10437595
关键词：
Affect Area Astrocytes Basal Ganglia Biochemical Blood - brain barrier anatomy Blood Vessels Brain Brain Pathology Brain region Cell Adhesion Molecules Cell Communication Cerebral Malaria Cerebrovascular system Cerebrum Characteristics Communicable Diseases Communication Corpus Callosum Data Development Disease Endothelium Environment Erythrocytes Exhibits Future G-Protein-Coupled Receptors Gene Chips Gene Expression Genes Genetic Transcription HIV Hemorrhage Heterogeneity Human Immune In Vitro Individual Infection Inflammatory Inflammatory Response Lead Liver Magnetic Resonance Imaging Metabolic Methods Microvascular Dysfunction Modeling Molecular Multiple Sclerosis Neurologic Neurons Oligodendroglia Organ Osmoregulation Oxygen Parasites Pathogenesis Pathologic Pathology Patients Pericytes Phenotype Physiological Property Research Sampling Signal Pathway Signal Transduction Stimulus Stroke Testing Therapeutic Trees Variant Vasodilation base blood-brain barrier disruption brain abnormalities brain cell brain endothelial cell brain tissue cell motility cerebral microvasculature deprivation frontal lobe gray matter immunocytochemistry microbial monocyte nervous system disorder neuroAIDS neurotropic neurovascular unit new therapeutic target precision medicine receptor response targeted treatment transcriptome vascular factor white matter

项目摘要

Project Summary In a variety of neurological conditions brain abnormalities have been observed in specific brain areas using MRI and immunohistological methods. These include patients suffering from stroke, small vessel disease, multiple sclerosis and infectious diseases, such as cerebral malaria (CM). Many neurological conditions contain an underlying vascular component. Brain vascular pathologies appear to differ according to vessel size and specific brain area the vessels reside in, including differences in vessels residing in gray matter (GM) versus white matter (WM). These differing pathologies are especially clear in CM: hemorrhagic punctae in WM but not in GM. Little is known of exactly what these differences are, the underlying causes of these vascular differences in GM versus WM and how these differences could relate to divergent neuropathological responses. We hypothesize that, cerebral microvessels derived from various GM and WM brain regions, exhibit differing properties, including different expression of transporters, receptors, junctional molecules and cell adhesion molecules. These differences are due to differences in the metabolic and functional needs of the direct physiological environment of these cerebral microvessel, including presence of astrocyte-neuronal versus pericyte-oligodendrocytes. These differences may be responsible for the varying inflammatory- and hemorrhagic- responses to stimuli, such as microbial stimulation, oxygen deprivation in stroke, or responses to therapeutics. In this proposal we intend to study the underlying differences of the brain’s vasculature using a comprehensive approach using human brain samples of different brain areas in combination with in-vitro BBB modeling. We propose to compare A) the global expression differences of the brain micro-vasculature. Thereafter, distinctive vascular markers that are specific for certain brain areas will be selected and their expression confirmed in different brain areas. B) Functional responses of brain endothelium will be tested using in vitro BBB models that have properties reflecting these vascular differences, e.g. WM and GM brain endothelium. We anticipate that this proposal will lead to clarification of vascular differences in the different brain areas and will offer an explanation for differing pathologies observed in neurological conditions. A better understanding of the vascular heterogeneity may lead to future development of novel targeted therapeutics.

项目总结