Macquarie University
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Effect of respiration and obstructive spinal pathology on cerebrospinal fluid flow

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posted on 2024-04-11, 02:25 authored by Donald Ekomobong Ogolo

Background: Disorders of cerebrospinal fluid (CSF) flow within the spinal cord such as syringomyelia have been associated with debilitating and occasionally lifelong neurologic incapacitation. Respiration, specifically inspiration (which causes a drop in intrathoracic pressure) has been established to be a major physiological driver of CSF flow within the spine. However, little is known about the effect of respiration on fluid flow within the spine in the presence of CSF obstruction. The aims of this study were: (i.) to evaluate the dynamics of CSF flow within the spinal subarachnoid space with spontaneous breathing (negative intrathoracic pressure) and mechanical ventilation (positive intrathoracic pressure) in the presence and absence of CSF obstruction; and (ii.) to assess the patterns of CSF flow into the spinal cord parenchyma with positive and negative intrathoracic pressures in the presence and absence of CSF obstruction.

Methods: This study was performed on 24 Sprague-Dawley rats, 12 with laminectomy only (controls) and 12 with laminectomy and CSF obstruction at C7/T1 level. Half of each of the above groups were then either mechanically ventilated or allowed to breathe spontaneously. Indocyanine green and ovalbumin AFO-647 fluorescent tracers were then injected into the cisterna magna and real time intraoperative imaging of the tracer flow within the spinal subarachnoid space was performed. Further microscopic quantification of axial distribution of the tracer within the cord parenchyma was also conducted. 

Results: The presence of CSF obstruction reduced craniocaudal flow of CSF tracers within the spinal subarachnoid space compared to the normal cord (p < 0.0001). Additionally, in the presence of CSF obstruction, application of mechanical ventilation reduced craniocaudal CSF tracer flow compared to spontaneous breathing at the earliest time point (p = 0.0099 at 2 minutes). Conversely, in the absence of cord constriction, mechanical ventilation enhanced craniocaudal flow of CSF tracers within the subarachnoid space at the earliest time point (p = 0.0373 at 30 seconds). In the presence of CSF obstruction, spontaneous breathing was associated with greater accumulation of tracer within the entire length of the cord from C2 to T4, when compared to mechanical ventilation (p = 0.0015). 

Conclusions: Obstruction to CSF flow within the spinal subarachnoid space might be crucial in the initiation and progression of fluid disorders of the cord such as syringomyelia. Furthermore, in the presence of CSF obstruction, positive pressure ventilation might be beneficial in preventing or reducing fluid accumulation within the cord.


Table of Contents

1. Introduction -- 2. Relevant anatomy of the spinal cord -- 3. CSF physiology -- 4. Pathology of syringomyelia -- 5. Animal models -- 6. Aims and hypotheses -- 7. Ethical approval -- 8. Methods – preoperative preparation -- 9. Methods – intraoperative procedure -- 10. Methods – perfusion-fixation -- 11. Methods – tissue processing -- 12. Methods – cryostat sectioning and image acquisition -- 13. Methods – image processing -- 14. Statistical analysis -- 15. Results -- 16. Discussion -- 17. Clinical relevance and future trend -- 18. Limitations and adverse events -- 19. Conclusions -- 20. References -- 21. Appendices

Awarding Institution

Macquarie University

Degree Type

Thesis MRes


Master of Research

Department, Centre or School

Macquarie Medical School

Year of Award


Principal Supervisor

Marcus Stoodley

Additional Supervisor 1

Sarah Hemley


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150 pages

Former Identifiers

AMIS ID: 279712

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