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Mesenchymal Stem Cell Therapy for Traumatic Brain Injury

Title: Mesenchymal Stem Cell Therapy for Traumatic Brain Injury: Cellular and Molecular Mechanisms.
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Name(s): Darkazalli, Ali, author
Levenson, Cathy W., professor directing dissertation
Strouse, Geoffrey F., university representative
Grant, Samuel C., committee member
Megraw, Timothy L., committee member
Wang, Zuoxin, committee member
Florida State University, degree granting institution
College of Medicine, degree granting college
Department of Biomedical Sciences, degree granting department
Type of Resource: text
Genre: Text
Issuance: monographic
Date Issued: 2015
Publisher: Florida State University
Place of Publication: Tallahassee, Florida
Physical Form: computer
online resource
Extent: 1 online resource (76 pages)
Language(s): English
Abstract/Description: Traumatic Brain Injury (TBI) gives rise to a progressive disease state that results in many adverse and long-term neurological consequences, including deficits in learning and memory, development of major depressive disorder, and increased likelihood of developing neurodegenerative diseases, as well as decreased life expectancy. Mesenchymal stem cells (MSC) have emerged as a promising cytotherapy for TBI and have been previously shown to improve numerous cellular and behavioral outcomes after brain injury including reduction of secondary apoptosis, restriction of immune cell infiltration, and improvements in cognitive deficits such as spatial learning and memory. A number of molecules secreted by MSC have been implicated in their therapeutic mechanism of action. However, no studies have been conducted to examine the how the MSC secretome collectively regulates the injury microenvironment to support the survival of intact brain tissue that would otherwise be subject to secondary injury. The present study, uses high throughput RNA sequencing (RNAseq) of cortical tissue from the TBI penumbra to assess the molecular effects of both TBI and subsequent treatment with intravenously delivered human mesenchymal stem cells (hMSC). TBI was found to disrupt expression of approximately one quarter of the rat protein-encoding genome. Remarkably, hMSC treatment was found to normalize 49% of all transcripts regulated by TBI. This study also investigates the therapeutic efficacy of hMSC against negative behavioral outcomes commonly associated with TBI, including depression, which is the most common long-term side effect of TBI in humans. We show for the first time that a stem cell-based therapy is capable of preventing trauma-induced depression. Using novel precision X-ray methods to selectively eliminate endogenous neural stem cells, this study further probes the cellular mechanisms that underlie hMSC efficacy to reveal that some, but not all, therapeutic benefits conferred by hMSC treatment are dependent on active proliferation of endogenous neural progenitor cells in the subventricular zone.
Identifier: FSU_2015fall_Darkazalli_fsu_0071E_12908 (IID)
Submitted Note: A Dissertation submitted to the Department of Biomedical Sciences in partial fulfillment of the requirements for the degree of Doctor of Philosophy.
Degree Awarded: Fall Semester 2015.
Date of Defense: November 3, 2015.
Keywords: Cytotherapy, Depression, Mesenchymal Stem Cells, Neural Progenitor Cells, Subventricular Zone, Traumatic Brain Injury
Bibliography Note: Includes bibliographical references.
Advisory Committee: Cathy W. Levenson, Professor Directing Dissertation; Geoffrey F. Strouse, University Representative; Samuel C. Grant, Committee Member; Timothy Megraw, Committee Member; Zuoxin Wang, Committee Member.
Subject(s): Neurosciences
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_2015fall_Darkazalli_fsu_0071E_12908
Owner Institution: FSU

Choose the citation style.
Darkazalli, A. (2015). Mesenchymal Stem Cell Therapy for Traumatic Brain Injury: Cellular and Molecular Mechanisms. Retrieved from http://purl.flvc.org/fsu/fd/FSU_2015fall_Darkazalli_fsu_0071E_12908