title: Delayed localized hypothermia reduces intracranial pressure following collagenase-induced intracerebral hemorrhage in rat.
abstract: Brain injury, such as from intracerebral hemorrhage (ICH), causes edema and raises intracranial pressure (ICP)--a potentially life-threatening complication. Clinical studies suggest that therapeutic hypothermia (TH) reduces edema and ICP after ICH. Similarly, animal studies show that TH can sometimes reduce edema, but whether ICP would be attenuated is not known. Here we tested whether 24-h delayed TH reduces edema and ICP in rats with severe striatal ICH (collagenase model). First, we showed that ICH increased epidural ICP (mean of 18 vs. 6.5mm Hg in controls), measured via telemetry. Second, we confirmed that delayed TH did not affect hematoma size at 7d ay (~65 vs. ~61 µL in controls). A cranial cooling device lowered striatal temperature to ~33 °C from 24 to 72 h after ICH. Third, we compared normothermic rats to those with TH that were rewarmed immediately or over 6h. Both TH protocols significantly reduced average and peak ICP by the second treatment day, and benefits persisted after rewarming. However, TH with slow rewarming failed to mitigate edema at 96 h (83.2% vs. 83.6% in controls) whereas rapid rewarming worsened edema (85.7%). Finally, we compared normothermic and TH rats without rewarming and found no impact on edema at 72 h (~81%). In summary, it appears that 24-h delayed local TH lowers ICP by a mechanism other than edema. Rapid rewarming worsens edema after local cooling, but this did not markedly impact ICP. Thus, TH should reduce ICP in patients with severe ICH, but not necessarily through mitigating edema.
authors.affiliation: Neuroscience and Mental Health Institute University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Roseleen F
authors.initials: RF
authors.lastname: John
authors.affiliation: Neuroscience and Mental Health Institute University of Alberta, Edmonton, Alberta, Canada; Department of Psychology, University of Alberta, Edmonton, Alberta, Canada. Electronic address: fcolbour@ualberta.ca.
authors.forename: Frederick
authors.initials: F
authors.lastname: Colbourne
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000209:etiology; D002543:Cerebral Hemorrhage / Q000150:complications*; D004195:Disease Models, Animal; D007036:Hypothermia, Induced / Q000379:methods*; D007427:Intracranial Pressure / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017694:Rewarming / Q000009:adverse effects / Q000379:methods
keywords: Animal model; Collagenase; Edema; Intracerebral hemorrhage; Intracranial pressure; Stroke; Therapeutic hypothermia