Dissertation/Thesis Abstract

Endogenous Proliferative Responses to Acute Trauma in Mammalian Models of Spinal Cord Injury
by McDonough, Ashley, Ph.D., University of California, Davis, 2013, 77; 3602158
Abstract (Summary)

Spinal cord injury (SCI) results in motor and sensory deficits, the severity of which depends on the level and extent of the injury. Animal models for SCI research include transection, contusion, and compression mouse models. This dissertation includes a review and a research paper that discuss the endogenous proliferative responses to spinal cord injury. In the review, we discuss the endogenous stem cell response to SCI in animal models. All SCI animal models experience a similar peak of cell proliferation three days after injury; however, each specific type of injury promotes a specific and distinct stem cell response. For example, the transection model results in a strong and localized initial increase of proliferation, while in contusion and compression models, the initial level of proliferation is lower but encompasses the entire rostro-caudal extent of the spinal cord. All injury types result in an increased ependymal proliferation, but only in contusion and compression models is there a significant level of proliferation in the lateral regions of the spinal cord. Finally, the fate of newly generated cells varies from mainly oligodendrocyte fate in contusion and compression to mostly astrocyte fate in the transection model. Here we will discuss the potential of endogenous stem/progenitor cell manipulation as a therapeutic tool to treat SCI. In the reprint of my research article, we use a mouse model of compression injury to better understand the proliferative properties and differentiation potential of the adult spinal cord after injury. After injury, adult mice were administered BrdU to label mitotic cells and sacrificed at different time-points for immunohistochemical analysis. Our data show that the rate of proliferation increased in all regions of the spinal cord one day after injury, peaked after three days, and remained elevated for at least 14 days after injury. Proliferation was greater at the injury epicenter than in rostral and caudal adjacent spinal segments. The number of proliferative cells and rate of proliferation varied between dorsal and ventral regions of the spinal cord and between the grey and white matter. Newly generated cells expressed markers for progenitor cells (Nestin and Olig2), oligodendrocytes (Sox10), astrocytes (S100b and GFAP), and microglia (Iba1), but not neuronal markers (Map2 and NeuN). Marker expression varied with regards to the dorso-ventral region, rostro-caudal proximity to the injury epicenter, and time after injury. At early time-points after injury, BrdU+ cells mainly expressed microglial/macrophage and astrocytic markers, while at these same time-points in control spinal cord the mitotic cells predominately expressed oligodendrocyte and oligodendrocyte progenitor cell markers. The profile of proliferation and cell fate marker expression indicates that after moderate compression, the spinal cord has the capacity to generate a variety of glial cells but not neurons, and that this pattern is space and time specific. Future studies should focus on ways to control proliferation and cell fate after injury to aid the development of cell replacement treatments for spinal cord injury.

Indexing (document details)
Advisor: Martinez-Cerdeno, Veronica
Commitee: Knoepfler, Paul S., Pleasure, David E.
School: University of California, Davis
Department: Cell and Developmental Biology
School Location: United States -- California
Source: DAI-B 75/03(E), Dissertation Abstracts International
Subjects: Neurosciences
Keywords: Acute trauma, Mammalian, Proliferation, Spinal cord injury
Publication Number: 3602158
ISBN: 978-1-303-53973-2
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