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Therapeutic potential of radial glial RG3.6 cells in rat spinal cord injury
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Therapeutic potential of radial glial RG3.6 cells in rat spinal cord injury
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Chang
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Yu-Wen
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Yu-Wen Chang
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Martin
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Martin Grumet
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Firestein
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Bonnie
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Bonnie L Firestein
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Nowakowski
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Richard
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Richard S Nowakowski
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Young
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Wise
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Wise Young
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Ratan
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Rajiv
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Advisory Committee
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Rajiv R Ratan
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Rutgers University
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Graduate School - New Brunswick
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theses
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2007
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2007
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English
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electronic
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xv, 138 pages
Abstract
Spinal cord injury (SCI) triggers a cascade of pathophysiological changes that lead to secondary tissue damage after the mechanical insult. Early after SCI, cells are disrupted and excitotoxic amino acids (e.g. glutamate) are released. Inflammatory cytokines and chemokines are quickly induced upon injury, followed by leukocyte infiltration (e.g. neutrophil and macrophage). Neurons and glia undergo massive necrotic cell death and apoptosis. Axons become progressively degenerated and extracellular substrate deposits in the lesion site, which leads to cyst and scar formation.
Cell-based therapies have been widely applied during SCI sub-acute phase and at least one mechanism associated with behavioral improvement is promotion of axonal remyelination and regeneration. However, the efficacy of cell transplantation at acute SCI and associated mechanism has rarely been studied.
Radial glial cells are essential in guiding and supporting neuronal migration during central nervous system development. They are neural stem cells and have trophic functions under certain conditions. In this thesis, our goal is to understand whether acute transplantation of radial glia can mitigate deleterious responses in the injured spinal cord tissue and promote functional recovery. RG3.6 is a stable neural stem cell clone derived from E13.5 cortex and has radial glial phenotypes including bipolar shape, expression of BLBP and GLAST, and support of neurite growth. Transplanted in normal spinal cord, RG3.6 retained radial glial phenotype and actively migrated along rostral-caudal axis of spinal cord and integrated nicely with host tissue. In SCI, acute transplantation of RG3.6 significantly improved locomotion recovery as early as 2 days post injury. The functional recovery may be associated with fewer infiltrating macrophages, less CSPG deposition, and more axonal preservation. At the molecular level, RG3.6 cell enhanced the expression of genes that are involved in tissue defense and stem cell development.
In summary, radial glia in acute SCI modulated host responses to the injury by mediating certain gene expressions at early times, suppressed neuroinflammation, and supported and reorganized axons during later phases. Our results provide different perspectives of cell-based therapy for acute SCI.
Cell-based therapies have been widely applied during SCI sub-acute phase and at least one mechanism associated with behavioral improvement is promotion of axonal remyelination and regeneration. However, the efficacy of cell transplantation at acute SCI and associated mechanism has rarely been studied.
Radial glial cells are essential in guiding and supporting neuronal migration during central nervous system development. They are neural stem cells and have trophic functions under certain conditions. In this thesis, our goal is to understand whether acute transplantation of radial glia can mitigate deleterious responses in the injured spinal cord tissue and promote functional recovery. RG3.6 is a stable neural stem cell clone derived from E13.5 cortex and has radial glial phenotypes including bipolar shape, expression of BLBP and GLAST, and support of neurite growth. Transplanted in normal spinal cord, RG3.6 retained radial glial phenotype and actively migrated along rostral-caudal axis of spinal cord and integrated nicely with host tissue. In SCI, acute transplantation of RG3.6 significantly improved locomotion recovery as early as 2 days post injury. The functional recovery may be associated with fewer infiltrating macrophages, less CSPG deposition, and more axonal preservation. At the molecular level, RG3.6 cell enhanced the expression of genes that are involved in tissue defense and stem cell development.
In summary, radial glia in acute SCI modulated host responses to the injury by mediating certain gene expressions at early times, suppressed neuroinflammation, and supported and reorganized axons during later phases. Our results provide different perspectives of cell-based therapy for acute SCI.
Note
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Ph.D.
Note
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Includes bibliographical references (p. 117-137).
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Topic
Neuroscience
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Spinal cord--Wounds and injuries
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Neuroglia
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Graduate School - New Brunswick Electronic Theses and Dissertations
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http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.15795
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doi:10.7282/T32V2GKH
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ETD doctoral
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Open
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Yu-Wen Chang
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Rutgers University. Graduate School - New Brunswick
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I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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