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dc.contributor.authorBarkho, Basam
dc.date.accessioned2010-02-09T22:03:24Z
dc.date.available2010-02-09T22:03:24Z
dc.date.issued2010-02-09T22:03:24Z
dc.date.submittedDecember 2009
dc.identifier.urihttp://hdl.handle.net/1928/10355
dc.description.abstractThe plasticity of adult neural stem/progenitor cells allows a differential response to a variety of environmental cues. Over the past decade, significant research efforts have been devoted into understanding the regulation of neural stem/progenitor cells due to their promising potential for cell replacement therapies in adult neurological diseases. It has been demonstrated that after brain injury both endogenous and grafted neural stem/progenitor cells have the ability to proliferate to expand their number, migrate long distances to the lesioned site and differentiate into new specific neurons to replace the ones that have been lost. All these procedure are regulated by extrinsic cue found in the microenvironment surrounding the neural stem/progenitor cells. Several chemokines and growth factors have been identified that stimulate the proliferation, differentiation, and migration of endogenous or exogenous neural stem/progenitor cells. The first part of this dissertation work (Chapter 5) identifies the role of several extrinsic factors expressed and secreted by hippocampal astrocytes that regulate the neuronal differentiation of adult neural stem/progenitor cells in the neurogenic region of the dentate gyrus. While in non-neurogenic regions, astrocytes secrete factors that inhibit the differentiation of adult neural stem/progenitor cells. Cell migration is an essential component of neurogenesis in both embryonic and adult brains. Many critical signaling factors and molecules are involved in governing the dynamic process of cell migration, which includes chemotaxis, cytoskeleton restructuring, nuclear translocation, and extracellular matrix remodeling. Extracellular molecules regulate the interaction and communication of the cell with its microenvironment. Investigators have shown that extracellular matrix and matrix remodeling factors play a critical role in directing stem cell migration during development and in the response to brain injury. Identification of the molecular pathways and mechanisms of these factors, involved in regulating stem cell fate choice and homing into the damaged areas, is vital for new treatments in brain injury. In the second part of this dissertation (Chapter 6), I focus on demonstrating that several matrix metalloproteinases are demonstrated to play a role in both the migration and differentiation of adult neural stem cells/progenitor in response to stroke-induced chemokines. The role of matrix metalloproteinase in differentiation may be the first evidence of extracellular molecules effecting the intrinsic regulation of adult neural stem/progenitor fate choice.en_US
dc.description.sponsorshipAmerican Heart Association - Pre-doctoral Fellowshipen_US
dc.language.isoen_USen_US
dc.subjectNeural Stem Cellsen_US
dc.subjectCell Migrationen_US
dc.subjectStem Cell Nicheen_US
dc.subjectDifferentiationen_US
dc.subjectBrain Injuryen_US
dc.subjectMatrix Metalloproteinaseen_US
dc.subject.lcshNeural stem cells--Adaptation
dc.subject.lcshNeural Stem Cells--Metabolism--Regulation
dc.subject.lcshAstrocytes
dc.subject.lcshExtracellular matrix
dc.subject.lcshChemokines
dc.subject.lcshMetalloproteinases
dc.subject.lcshCell migration
dc.titleAdult neural stem/progenitor cells in response to their microenvironment : proliferation, differentiation, and migrationen_US
dc.typeDissertationen_US
dc.description.degreeNeurosciencesen_US
dc.description.levelDoctoralen_US
dc.description.departmentUniversity of New Mexico. Biomedical Sciences Graduate Programen_US
dc.description.advisorZhao, Xinyu
dc.description.committee-memberCunningham, Lee Anna
dc.description.committee-memberMcGuire, Paul
dc.description.committee-memberWilson, Michael


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