Document text
Principal Investigator: Jae K Lee
Organization: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
Fiscal Year: 2019
Award: $481,810
Funding agency: National Institute of Neurological Disorders and Stroke
PROJECT SUMMARY/ABSTRACT
After spinal cord injury (SCI), the injury site is filled with cellular debris, especially myelin debris that creates a
very unique lipid-dense environment. Macrophages are the predominant phagocyte that are responsible for
debris-clearance, but this process is not only inefficient, it is also maladaptive. The excessive amount of myelin
debris present at the injury site leads to formation lipid-laden macrophages (a.k.a. foamy macrophages) that
become pro-inflammatory and contribute to tissue regeneration failure. In addition to macrophages, microglia
and fibroblasts also become foam cells. Therefore, understanding the mechanisms of myelin debris uptake and
catabolism after SCI may lead to novel therapeutic targets to promote repair after SCI. In this application, we
will investigate the mechanism of myelin debris uptake as well as the export of its catabolic byproduct in
macrophages, microglia, and fibroblasts after SCI. In addition, we will test the therapeutic potential of novel
nanoparticles that can target the uptake and efflux mechanisms.
Terms: <ABCA1><ABCA1 protein><ATP binding cassette transporter 1><Affect><Assay><Behavioral><Bioassay><Biologic Assays><Biological Assay><Blood leukocyte><Bruise><CD36><CD36 gene><Catabolism><Cell Body><Cells><Cervical><Common Rat Strains><Contusions><Data><Environment><Equilibrium><Failure><Fibroblasts><Foam Cells><Foamy Macrophage><GP3B><GP4><GPIV><Gene Expression Monitoring><Gene Expression Pattern Analysis><Gene Expression Profiling><Gene Transcription><Genes><Genetic><Genetic Transcription><Goals><HDLDT1><Hortega cell><In Vitro><Inflammation><Inflammatory><Injury><Intermediary Metabolism><Lead><Leukocytes><Leukocytes Reticuloendothelial System><Lipid-Laden Macrophage><Lipids><Marrow leukocyte><Mediating><Metabolic Processes><Metabolism><Microglia><Modeling><Molecular><Myelin><Nervous System Diseases><Neurologic Disorders><Neurological Disorders><Pathogenesis><Pathologic><Pathology><Pathway interactions><Patients><Pb element><Peripheral><Phagocytes><Phagocytic Cell><Phagocytosis><Phenotype><Pinocytosis><Population><Process><RNA Expression><Rat><Rats Mammals><Rattus><Recovery of Function><Role><SCARB3><Site><Spinal Cord Trauma><Spinal Trauma><Spinal cord injured><Spinal cord injuries><Spinal cord injury><Testing><Therapeutic><Therapeutic Effect><Therapeutic Uses><Transcript Expression Analyses><Transcript Expression Analysis><Transcription><Traumatic Myelopathy><White Blood Cells><White Cell><acetyl-LDL receptor><acetylated LDL receptor><amebocyte><balance><balance function><cell transformation><cell type><cholesterol-efflux regulatory protein><clinical relevance><clinically relevant><disability><experiment><experimental research><experimental study><fat metabolism><functional recovery><gene expression analysis><gene expression assay><gitter cell><heavy metal Pb><heavy metal lead><in vivo><insight><lipid metabolism><macrophage><mesoglia><microglial cell><microgliocyte><mouse model><murine model><nano particle><nano-sized particle><nanoparticle><nanosized particle><nervous system disorder><neurological disease><new drug target><new druggable target><new pharmacotherapy target><new therapeutic target><new therapy target><novel><novel drug target><novel druggable target><novel pharmacotherapy target><novel therapeutic target><novel therapy target><overexpress><overexpression><pathway><perivascular glial cell><prevent><preventing><recruit><regenerate new tissue><regenerating damaged tissue><repair><repaired><scavenger receptor><social role><spinal cord regeneration><therapeutic evaluation><therapeutic testing><tissue regeneration><tissue repair><transcriptional profiling><transformed cells><uptake><white blood cell><white blood corpuscle>