Investigating the Influence of Therapeutic Hypothermia on Stroke-Induced Intracranial Pressure in a Rat Model of Intracerebral Hemorrhage

Abstract

Elevated intracranial pressure (ICP) is a potentially life threatening complication after intracerebral hemorrhagic stroke (ICH). Animal and clinical studies suggest that mild (~33ºC) therapeutic hypothermia (TH) reduces ICP after ischemic stroke and traumatic brain injury (TBI). Since TH has also been shown to reduce edema after several neurological conditions, and edema is widely considered a key contributor to ICP, it is hypothesized that ICP management might be achieved through edema reduction. Thus, the current thesis evaluated the influence of brain-selective TH on ICP in a rat model of ICH. This thesis evaluated whether brain selective-cooling aggravated bleeding in the collagenase-induced ICH model, and tested whether brain cooling reduced ICP after ICH, or the re-warming rate mattered. ICP was measured for 4 days using telemetry pressure transmitters in untethered awake rats subjected to a large-collagenase induced ICH. Delayed cooling 24 hours after ICH did not worsen bleeding, and so TH treatment was delayed for 24 hours in all cooling experiments. Brain-selective hypothermia significantly reduced mean and peak ICP. On the contrary, fast-rewarming worsened edema on day 4, but this did not noticeably affect ICP responses. Lastly, increases in edema did not correlate with increases in ICP. These findings suggest that factors other than edema may better predict ICP, and further pre-clinical work is needed to provide better insight into cerebral pressure management.