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Fluid physiology in the spinal cord and subarachnoid space with relevance to syringomyelia pathogenesis

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posted on 2022-03-28, 19:09 authored by Shinuo Liu
There is mounting evidence that disruption of cerebrospinal fluid (CSF) circulation and CSF/interstitial fluid exchange is likely to contribute to a number of central nervous system disorders including syringomyelia. However, there is an incomplete understanding of the pathways of spinal fluid flux, in particular, fluid outflow. Moreover, the physiological factors that govern CSF flow in the spinal subarachnoid space (SAS) and fluid transport in the spinal cord have not been well studied. The aims in this thesis were to determine 1) the fluid outflow pathways in the normal spinal cord and 2) the effects of heart rate, blood pressure and respiration, specifically intrathoracic pressure, on fluid flow in the SAS, as well as into and out of the spinal interstitium. Fluorescent tracers were injected into the cisterna magna and the cervicothoracic spinal cord parenchyma of Sprague Dawley rats. Various fluorescence imaging techniques were performed either in vivo in real-time, or ex vivo in perfusion-fixed extracted brain and spinal cord specimens. The macroscopic and microscopic redistribution of tracer within and around the spinal cord, particularly in relationship to vascular structures, was characterised. To investigate the effects of respiration, heart rate and blood pressure on fluid dynamics, each physiological parameter was carefully controlled and separately manipulated. Free breathing animals (in which cycles of negative and positive intrathoracic pressure are generated) had significantly greater flow of CSF in the SAS as well as inflow of tracer into the spinal cord compared with mechanically ventilated control rats (positive intrathoracic pressure only). Hypertension and tachycardia had no significant effect on CSF flow in the SAS. Hypertension produced conflicting results but likely had a modest effect on inflow. Increased tracer influx was not observed with tachycardia. Both tachycardia and hypertension stimulated tracer efflux, but respiration was not found to affect spinal interstitial clearance. Spinal intramedullary movement of tracer was slow, and its redistribution was limited by isotropic and anisotropic properties of white and grey matter. Perivascular spaces of all vessel types provided preferential pathways for both tracer influx and efflux to pial and ependymal surfaces. Tracer deposited within the internal basement membrane of the tunica media of arteries and arterioles. Intrathoracic pressure has a significant effect on spinal CSF flow and parenchymal fluid ingress. Arterial pulsations play a smaller role in SAS hydrodynamics but have profound effects on spinal interstitial fluid homeostasis, particularly outflow -- abstract.


Table of Contents

Chapter 1. Introduction -- Chapter 2. Aims and hypotheses -- Chapter 3. Fluid outflow in the rat spinal cord: the role of perivascular and paravascular pathways -- Chapter 4. Intrathoracic pressure and arterial pulsations exert different driving forces on spinal cerebrospinal and interstitial fluid flow -- Chapter 5. General discussion -- Chapter 6. Conclusions -- Appendices


Bibliography: pages 215-244 Theoretical thesis.

Awarding Institution

Macquarie University

Degree Type

Thesis PhD


PhD, Macquarie University, Faculty of Medicine and Health Sciences, Department of Clinical Medicine

Department, Centre or School

Department of Clinical Medicine

Year of Award


Principal Supervisor

Marcus A. Stoodley

Additional Supervisor 1

Sarah J. Hemley


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