Importance of CSF circulation following ischaemic stroke: A novel MRI investigation of CSF parenchymal flow

Alshuhri, Mohammed Shenan (2021) Importance of CSF circulation following ischaemic stroke: A novel MRI investigation of CSF parenchymal flow. PhD thesis, University of Glasgow.

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It has been proposed that intracranial pressure (ICP) elevation and collateral failure are responsible for unexplained early neurological deterioration (END) in stroke. Our aim was to investigate whether cerebrospinal fluid (CSF) dynamics, rather than oedema, are responsible for elevation of ICP after ischaemic stroke. Permanent middle cerebral artery occlusion (pMCAO) was induced with anintraluminal filament. At 24 hours after stroke, baseline ICP was
measured, and dynamics were probed via a steady-state infusion method. For the first time, we found a significant correlation between the baseline ICP at 24 hours post-stroke and the value of CSF outflow resistance. Results show that CSF outflow resistance, rather than oedema, was the mechanism responsible for ICP elevation following ischaemic stroke. This challenges current concepts and suggests the possibility that intracranial hypertension may be occurring undetected in a much wider range of stroke patients than is currently considered to be the case.

Over the last decade, there has been significant renewed interest in the anatomical pathways and physiological mechanisms for the circulation of CSF. The glymphatic system is one such pathway that has been recently characterised. This network drives CSF into the brain along periarterial spaces and interstitial fluid (ISF) out along perivenous spaces. Aquaporin-4 (AQP4) water channels, densely expressed at the vascular endfeet of astrocytes, facilitate glymphatic transport. Glymphatic failure has been linked to a broad range of neurodegenerative diseases including ischaemic stroke. Accordingly, if the glymphatic circulation is a major outflow route for CSF, glymphatic dysfunction following ischaemic stroke could alter CSF dynamics and, therefore, ICP.

Nevertheless, the glymphatic hypothesis is still controversial. All in vivo and biomechanical modelling studies that have investigated the glymphatic system have been based on utilizing a solute tracer to track the movement of CSF within the intracranial space. Since 99% of CSF is water, it is questionable whether nonwater tracer molecules can ever show the real dynamic flow of CSF. Hence, we sought the develop of a new MRI method to directly image CSF dynamics in-vivo, by exploiting an isotopically enriched MRI tracer, namely, H217O. Our results reveal glymphatic flow that is dramatically faster and more extensive than previously thought. Moreover, we confirm the critical role of aquaporin-4 (AQP4) channels in glymphatic flow by imaging CSF water dynamics in the brain using H217O alongside a potent blocker of AQP4. We hope in futurethat this new method can be used to investigate the responsible for
the increased CSF resistance and ICP elevation following ischaemic stroke.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Subjects: Q Science > QP Physiology
Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
Supervisor's Name: Holmes, Dr. William
Date of Award: 2021
Depositing User: Theses Team
Unique ID: glathesis:2021-82303
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 02 Jul 2021 14:18
Last Modified: 13 Oct 2022 13:45
Thesis DOI: 10.5525/gla.thesis.82303
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