Change in CSF Dynamics Responsible for ICP Elevation After Ischemic Stroke in Rats: a New Mechanism for Unexplained END?

Abstract

It has been proposed that intracranial pressure (ICP) elevation and collateral failure are responsible for unexplained early neurological deterioration (END) in stroke. The study’s aims were to investigate whether cerebral spinal fluid (CSF) dynamics, rather than edema, are responsible for elevation of ICP after ischemic stroke. Permanent middle cerebral artery occlusion (pMCAO) was induced with an intraluminal filament. At 24 h after stroke, baseline ICP was measured and CSF dynamics were probed via a steady-state infusion method. Diffusion-weighted imaging (DWI) and T2-weighted magnetic resonance imaging were performed to define cerebral ischemic damage and the volume of brain swelling. We found that the pMCAO group exhibited a significant increase in CSF outflow resistance (2.27 ± 0.15 mmHg μL−1 min) compared with the sham group (0.93 ± 0.06 mmHg μL−1 min, p = 0.002). There was no correlation between mean ICP at 24 h post-pMCAO and edema (r2 = − 0.03, p = 0.5) or infarct volumes (r2 = 0.09, p = 0.5). However, for the first time, we found a significant correlation between the baseline ICP at 24 h post-stroke and the value of CSF outflow resistance. Results show that CSF outflow resistance, rather than edema, was the mechanism responsible for ICP elevation following ischemic 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. In addition, this further supports the hypothesis that unexplained early neurological deterioration is the result of elevated ICP, leading to reduced collateral flow and cerebral perfusion.

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Acknowledgments

We would like to acknowledge the contribution of Dr. Robin Young (Robertson Centre for Biostatistics, University of Glasgow) for valuable statistical advice and discussions.

Funding

MSA would like to acknowledge funding from Ministry of Higher Education in Saudi Arabia.

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Correspondence to William M. Holmes.

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Alshuhri, M.S., Gallagher, L., McCabe, C. et al. Change in CSF Dynamics Responsible for ICP Elevation After Ischemic Stroke in Rats: a New Mechanism for Unexplained END?. Transl. Stroke Res. 11, 310–318 (2020). https://doi.org/10.1007/s12975-019-00719-6

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Keywords

  • Intracranial pressure
  • Early neurological deterioration
  • Ischemic stroke
  • Cerebrospinal fluid
  • MRI