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

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 24h after moderate and small strokes. (2) Short-duration hypothermia-rewarming, instituted before intracranial pressure elevation, prevents this 24h 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 24h. Wistars were randomized to 2 center dot 5h hypothermia (32 center dot 5 degrees C) or normothermia, commencing 1h after stroke. Results In Long-Evans rats (n=5), intracranial pressure increased from 10 center dot 9 +/- 4 center dot 6mmHg at baseline to 32 center dot 4 +/- 11 center dot 4mmHg at 24h, infarct volume was 84 center dot 3 +/- 15 center dot 9mm3. In normothermic Wistars (n=10), intracranial pressure increased from 6 center dot 7 +/- 2 center dot 3mmHg to 31 center dot 6 +/- 9 center dot 3mmHg, infarct volume was 31 center dot 3 +/- 18 center dot 4mm3. In hypothermia-treated Wistars (n=10), 24h intracranial pressure did not increase (7 center dot 0 +/- 2 center dot 8mmHg, P<0 center dot 001 vs. normothermia), and infarct volume was smaller (15 center dot 4 +/- 11 center dot 8mm3, P<0 center dot 05). Conclusions We saw major intracranial pressure elevation 24h after stroke in two rat strains, even after small strokes. Short-duration hypothermia prevented the intracranial pressure rise, an effect sustained for at least 18h after rewarming. The findings have potentially important implications for design of future clinical trials.