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Post-traumatic syringomyelia: investigations into pathophysiology

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thesis
posted on 28.03.2022, 18:28 authored by Johnny Ho Yin Wong
Background and object: Post-traumatic syringomyelia is a disabling neurological condition that occurs in approximately 28% of patients following a spinal cord injury, although not all of these cases may be symptomatic. The pathogenesis of syringomyelia is not adequately understood, and treatment is associated with high failure rates. More effective treatment can only be developed when a better understanding of the pathophysiological processes is achieved. The objectives in this thesis were: (i) to determine the biochemical profile of syrinx fluid; (ii) to develop a reproducible and relevant post-traumatic syringomyelia model; (iii) to characterise the nature of syrinx inflow and outflow; (iv) to investigate the possibility of CSF-arterial pulsation delay; and (v) to determine the effect of modulating aquaporin-4 (AQP4) water channel function. Methods: Human and animal studies were performed. Human syrinx and spinal CSF samples were obtained intraoperatively for biochemical analyses. A computer-controlled motorised spinal cord impactor was used to develop a rodent model of post-traumatic syringomyelia. Syrinx fluid inflow and outflow were assessed in sheep and rodent models using kaolin to induce spinal arachoniditis, and horseradish peroxidase and fluorescent-labelled ovalbumin as CSF tracers. Telemetry pressure transmission was performed in a sheep arachnoiditis model. AQP4 expression and modulation were evaluated on rodent impactor and excitotoxic models. Results: Syrinx fluid had a similar biochemical profile to CSF. A reliable direct-impact model was developed with histological resemblance to human syrinxes. In the presence of arachnoiditis, CSF flow into the spinal cord was increased along perivascular spaces with progressive CSF pulsation delay. Fluid outflow occurred in a diffuse manner into the interstitial space in a new large animal model. AQP4 expression was increased in the impactor model, and AQP4 inhibition produced larger syrinxes with increased AQP4 expression in the surrounding areas. Conclusions: Multiple factors contribute to post-traumatic syringomyelia development beyond the initial spinal cord trauma. Arachnoiditis, CSF pulsations, outflow and aquaporins are likely to play important roles in syrinx expansion. Modulation of AQP4 and other molecular processes may be potential avenues for development of new treatments.

History

Table of Contents

Chapter 1. Introduction -- Chapter 2. General methods -- Chapter 3. Biochemical analysis of syringomyelia fluid -- Chapter 4. Direct-trauma model of post-traumatic syringomyelia with a computer controlled motorised spinal cord impactor -- Chapter 5. Cerebrospinal fluid flow in spinal arachnoiditis using horseradish peroxidase (HRP) -- Chapter 6. Cerebrospinal fluid flow in spinal arachnoiditis using Alexa-Fluor ovalbumin (AFO) -- Chapter 7. In-vivo telemetry of cerebrospinal fluid pulsations in spinal arachnoiditis -- Chapter 8. Fluid outflow in large animal model of post-traumatic syringomyelia -- Chapter 9. Aquaporin-4 and Aquaporin-1 expression in spinal cord injury and post-traumatic syringomyelia -- Chapter 10. The effect of Aquaporin-4 modulation in a rodent model of post-traumatic syringomyelia -- Chapter 11. General discussion -- Chapter 12. Conclusions. -- Chapter 13. Appendices -- Chapter 14. References.

Notes

Bibliography: pages 327-371 Empirical thesis.

Awarding Institution

Macquarie University

Degree Type

Thesis PhD

Degree

PhD, Macquarie University, Faculty of Human Sciences, Australian School of Advanced Medicine

Department, Centre or School

Australian School of Advanced Medicine

Year of Award

2014

Principal Supervisor

Marcus Stoodley

Rights

Copyright Johnny Ho Yin Wong 2013. Copyright disclaimer: http://mq.edu.au/library/copyright

Language

English

Extent

1 online resource (372 pages) colour illustrations

Former Identifiers

mq:71915 http://hdl.handle.net/1959.14/1279428