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

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 degrees C. At 18 h post-stroke, CSF outflow resistance was measured using a steady-state infusion method. Results: Hypothermia to 33 degrees C prevented ICP elevation 18 h post-stroke (hypothermia increment ICP = 0.8 +/- 3.6 mmHg vs. normothermia increment ICP = 4.4 +/- 2.0 mmHg, p = 0.04) and reduced infarct volume 24 h post-stroke (hypothermia = 78.6 +/- 21.3 mm(3) vs. normothermia = 108.1 +/- 17.8 mm(3); p = 0.01). Hypothermia to 33 degrees C did not result in a significant reduction in CSF outflow resistance compared with normothermia controls (0.32 +/- 0.36 mmHg/mu L/min vs. 1.07 +/- 0.99 mmHg/mu L/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.