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Role of notch signaling after traumatic brain injury in a transgenic mouse model
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Anderson, Jeremy. Role of notch signaling after traumatic brain injury in a transgenic mouse model. Retrieved from https://doi.org/doi:10.7282/t3-695z-w777

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TitleRole of notch signaling after traumatic brain injury in a transgenic mouse model
NameAnderson, Jeremy (author); Cai, Li (chair); Firestein, Bonnie (internal member); Pang, Zhiping (internal member); Alder, Janet (outside member); Rutgers University; School of Graduate Studies
Date Created2019
Other Date2019-10 (degree)
SubjectBiomedical Engineering, Neural stem cells, Transgenic mice
Extent1 online resource (xiii, 100 pages) : illustrations
DescriptionTraumatic brain injury (TBI) is a leading cause of disability and death in the United States and worldwide. Endogenous neural stem/progenitor cells (NSPCs) in the adult are a potential source for injury recovery. However, much about the response of injury-activated NSPCs is still unknown. Notch signaling is critical for maintaining NSPC status during embryonic development and transiently activated after injury. In the first part of this thesis, the role of Notch signaling after TBI is investigated using a Notch1CR2-GFP transgenic mouse model. During development, GFP mainly marks interneuron progenitor cells. A closed head injury (CHI) in this transgenic mouse was performed to determine the response of injury-activated NSPCs. CHI induces neuroinflammation, cell death, and the expression of typical TBI markers, validating the animal model. In addition, CHI induces cell proliferation in GFP+ cells expressing NSPC markers, e.g., Notch1 and Nestin. A significant higher percentage of GFP+ GABAergic interneurons was observed in the CHI brain, with no significant change in oligodendrocyte lineage between the CHI and sham animal groups. Since injury is known to activate astrogliosis, these results suggest that injury-induced GFP+ NSPCs preferentially differentiate into GABAergic neurons. Our study establishes that Notch1CR2-GFP transgenic mouse is a useful tool for the study of NSPC behavior in vivo after TBI.
In the second part of this thesis, the role of Gsx1, a neurogenic transcription factor, on promoting Notch1 expression and neurogenesis is investigated. A lentivirus system is used to deliver Gsx1 at the injury site after closed head injury (CHI) in the Notch1CR2-GFP transgenic mice. We identify that CHI increases GFP+ cell, during the acute phase of TBI and increasingly label neurons during the chronic phase of TBI. Lentivirus-mediated Gsx1 overexpression increases Notch1 expressing cells in the cerebral cortex and hippocampus; these virally transduced cells proliferate and mark NSPCs during the subacute phase of TBI and primarily label glutamatergic neurons during the chronic phase of TBI. The role of Gsx1 promoting Notch signaling and neurogenesis after TBI represents a new therapeutic for the treatment of TBI. Unveiling the potential of NSPCs to TBI (e.g., proliferation and differentiation) will identify new therapeutic strategy for the treatment of brain trauma.
NotePh.D.
NoteIncludes bibliographical references
Genretheses, ETD doctoral
Persistent URLhttps://doi.org/doi:10.7282/t3-695z-w777
LanguageEnglish
CollectionSchool of Graduate Studies Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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