Decreased Intracranial Pressure Elevation and Cerebrospinal Fluid Outflow Resistance: A Potential Mechanism of Hypothermia Cerebroprotection Following Experimental Stroke.

Daniel Omileke,Adjanie Patabendige,Kirsten Coupland,Debbie Pepperall,Steven W Bothwell,Neil J Spratt,Daniel J Beard

doi:10.3390/brainsci11121589

Abstract

Background: Elevated intracranial pressure (ICP) occurs 18–24 h after ischaemic stroke and is implicated as a potential cause of early neurological deterioration. Increased resistance to cerebrospinal fluid (CSF) outflow after ischaemic stroke is a proposed mechanism for ICP elevation. Ultra-short duration hypothermia prevents ICP elevation 24 h post-stroke in rats. We aimed to determine whether hypothermia would reduce CSF outflow resistance post-stroke. Methods: Transient middle cerebral artery occlusion was performed, followed by gradual cooling to 33 °C. At 18 h post-stroke, CSF outflow resistance was measured using a steady-state infusion method. Results: Hypothermia to 33 °C prevented ICP elevation 18 h post-stroke (hypothermia ∆ICP = 0.8 ± 3.6 mmHg vs. normothermia ∆ICP = 4.4 ± 2.0 mmHg, p = 0.04) and reduced infarct volume 24 h post-stroke (hypothermia = 78.6 ± 21.3 mm3 vs. normothermia = 108.1 ± 17.8 mm3; p = 0.01). Hypothermia to 33 °C did not result in a significant reduction in CSF outflow resistance compared with normothermia controls (0.32 ± 0.36 mmHg/µL/min vs. 1.07 ± 0.99 mmHg/µL/min, p = 0.06). Conclusions: Hypothermia treatment was protective in terms of ICP rise prevention, infarct volume reduction, and may be implicated in CSF outflow resistance post-stroke. Further investigations are warranted to elucidate the mechanisms of ICP elevation and hypothermia treatment.

Highlights

We have previously demonstrated that there is a damaging, transient increase in intracranial pressure (ICP) occurring 18–24 h post-stroke in rats [1,2,3,4,5,6]
We have previously demonstrated that ultra-short duration hypothermia, using clinically relevant cooling rates, prevents ICP elevation and reduces infarct volume 24 h post-stroke in rats [14]
We aimed to investigate whether ultra-short duration hypothermia using clinically relevant cooling rates reduces cerebrospinal fluid (CSF) outflow resistance 18 h following experimental stroke, when compared with normothermia controls

Summary

Introduction

We have previously demonstrated that there is a damaging, transient increase in intracranial pressure (ICP) occurring 18–24 h post-stroke in rats [1,2,3,4,5,6]. Short-duration hypothermia is a potential therapy and has previously been shown to prevent this elevated pressure following experimental stroke [1,2,4]. Increased resistance to cerebrospinal fluid (CSF) outflow after ischaemic stroke is a proposed mechanism for ICP elevation. We aimed to determine whether hypothermia would reduce CSF outflow resistance post-stroke. Conclusions: Hypothermia treatment was protective in terms of ICP rise prevention, infarct volume reduction, and may be implicated in CSF outflow resistance post-stroke. Further investigations are warranted to elucidate the mechanisms of ICP elevation and hypothermia treatment

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Conclusion