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Developing Experimental Models of Non-Traumatic Spinal Cord Injury

Timms, Katherine Victoria (2020) Developing Experimental Models of Non-Traumatic Spinal Cord Injury. Integrated PhD and Master thesis, University of Leeds.

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Over 50% of non-traumatic spinal cord injuries (NTSCI) are caused by mechanical compression either due to osteophytes in degenerative disease, or tumours (New et al., 2014). The pathophysiology of NTSCI is poorly understood, with no distinct injury cascade (Karadimas et al., 2013). The aim of this project was to evaluate cellular responses to mechanical insults in the context of NTSCI. In-vitro, a model was developed to apply high and low velocity compression to astrocyte-seeded collagen hydrogels. Outcomes included hydrogel contraction, GFAP expression, cellular shape, and cytokine release. In-vivo a balloon lesion model was modified to induce a non-traumatic ventral lesion, by developing an injection port and inflating over 3 days. Functional deficits and histological outcomes were assessed. In-vitro, 100 mm.s-1 compression elicited an astrogliotic and inflammatory response from day 11, indicative of TSCI. This comprised a significant increase in GFAP area per cell, astrocyte ramification, and IL-6 expression. Conversely, at <100 mm.s-1, no differences were observed. The findings of this study suggest slow compression of astrocytes alone does not induce NTSCI. In-vivo, surgery was undertaken on 10 animals (including 3 shams). In injury groups, functional deficits were observed , which increased with each inflation. Animals were grouped into mild and severe based on their motor function (severe animals exhibited paraplegia). Minimum motor function correlated with minimum cross-sectional area, and greater parenchyma disruption. In the severe group only, there was a trend of mild astrogliosis, demyelination and vasculature narrowing at the epicentre. This corresponds with the wider literature, where demyelination and disruption to the vasculature are hypothesised to be involved in NTSCI pathology. Overall, in-vitro and in-vivo models of NTSCI have been successfully developed. Physiological changes were observed in both models, with differences to TSCI. Further investigations can be undertaken to understand the pathology of NTSCI.

Item Type: Thesis (Integrated PhD and Master)
Keywords: spinal cord injury
Academic Units: The University of Leeds > Faculty of Engineering (Leeds) > School of Mechanical Engineering (Leeds) > Institute of Medical and Biological Engineering (iMBE)(Leeds)
Identification Number/EthosID: uk.bl.ethos.805353
Depositing User: Dr Katherine Victoria Timms
Date Deposited: 12 May 2020 16:26
Last Modified: 11 Jun 2020 09:53
URI: http://etheses.whiterose.ac.uk/id/eprint/26511

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