Short-duration hypothermia after ischemic stroke prevents delayed intracranial pressure rise

Authors

  • L. A. Murtha,

    1. University of Newcastle and Hunter Medical Research Institute, School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, NSW, Australia
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    • These authors contributed equally to this work.
  • D. D. McLeod,

    1. University of Newcastle and Hunter Medical Research Institute, School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, NSW, Australia
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    • These authors contributed equally to this work.
  • S. K. McCann,

    1. University of Newcastle and Hunter Medical Research Institute, School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, NSW, Australia
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  • D. Pepperall,

    1. University of Newcastle and Hunter Medical Research Institute, School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, NSW, Australia
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  • S. Chung,

    1. University of Newcastle and Hunter Medical Research Institute, School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, NSW, Australia
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  • C. R. Levi,

    1. University of Newcastle and Hunter Medical Research Institute, School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, NSW, Australia
    2. Hunter New England Local Health District, Department of Neurology, John Hunter Hospital, Hunter Region M.C., NSW, Australia
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  • M. B. Calford,

    1. University of Newcastle and Hunter Medical Research Institute, School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, NSW, Australia
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  • N. J. Spratt

    Corresponding author
    1. University of Newcastle and Hunter Medical Research Institute, School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, NSW, Australia
    2. Hunter New England Local Health District, Department of Neurology, John Hunter Hospital, Hunter Region M.C., NSW, Australia
    • Correspondence: Neil Spratt, Department of Neurology, John Hunter Hospital, Locked Bag 1, Hunter Region Mail Centre, NSW 2310, Australia.

      E-mail: Neil.Spratt@newcastle.edu.au

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  • Conflict of interest: The authors declare no potential conflict of interest.
  • Funding: This work was supported by a NHMRC Program Grant #454417 and research support from the Hunter Medical Research Institute from funds donated by the Greater Building Society. N. Spratt received a NHMRC training fellowship, #455632. L. Murtha received a student grant from the National Stroke Foundation (Australia). D. McLeod and N. Spratt received a project grant from the National Stroke Foundation (Australia).

Abstract

Background

Intracranial pressure elevation, peaking three to seven post-stroke is well recognized following large strokes. Data following small–moderate stroke are limited. Therapeutic hypothermia improves outcome after cardiac arrest, is strongly neuroprotective in experimental stroke, and is under clinical trial in stroke. Hypothermia lowers elevated intracranial pressure; however, rebound intracranial pressure elevation and neurological deterioration may occur during rewarming.

Hypotheses

(1) Intracranial pressure increases 24 h after moderate and small strokes. (2) Short-duration hypothermia-rewarming, instituted before intracranial pressure elevation, prevents this 24 h intracranial pressure elevation.

Methods

Long-Evans rats with two hour middle cerebral artery occlusion or outbred Wistar rats with three hour middle cerebral artery occlusion had intracranial pressure measured at baseline and 24 h. Wistars were randomized to 2·5 h hypothermia (32·5°C) or normothermia, commencing 1 h after stroke.

Results

In Long-Evans rats (n = 5), intracranial pressure increased from 10·9 ± 4·6 mmHg at baseline to 32·4 ± 11·4 mmHg at 24 h, infarct volume was 84·3 ± 15·9 mm3. In normothermic Wistars (n = 10), intracranial pressure increased from 6·7 ± 2·3 mmHg to 31·6 ± 9·3 mmHg, infarct volume was 31·3 ± 18·4 mm3. In hypothermia-treated Wistars (n = 10), 24 h intracranial pressure did not increase (7·0 ± 2·8 mmHg, P < 0·001 vs. normothermia), and infarct volume was smaller (15·4 ± 11·8 mm3, P < 0·05).

Conclusions

We saw major intracranial pressure elevation 24 h after stroke in two rat strains, even after small strokes. Short-duration hypothermia prevented the intracranial pressure rise, an effect sustained for at least 18 h after rewarming. The findings have potentially important implications for design of future clinical trials.

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