title: Examining potential side effects of therapeutic hypothermia in experimental intracerebral hemorrhage.
abstract: Studies treating intracerebral hemorrhage (ICH) with therapeutic hypothermia (TH) have shown inconsistent benefits. We hypothesized that TH's anti-inflammatory effects may be responsible as inflammatory cells are essential for removing degrading erythrocytes. Here, we subjected rats to a collagenase-induced striatal ICH followed by whole-body TH (∼33℃ for 11-72 h) or normothermia. We used X-ray fluorescence imaging to spatially quantify total and peri-hematoma iron three days post-injury. At three and seven days, we measured non-heme iron levels. Finally, hematoma volume was quantified on one, three, and seven days. In the injured hemisphere, total iron levels were elevated ( p < 0.001) with iron increasing in the peri-hematoma region ( p = 0.007). Non-heme iron increased from three to seven days (p < 0.001). TH had no effect on any measure of iron ( p ≥ 0.479). At one and three days, TH did not affect hematoma volume ( p ≥ 0.264); however, at seven days there was a four-fold increase in hematoma volume in 40% of treated animals ( p = 0.032). Thus, even when TH does not interfere with initial increases in total and non-heme iron or its containment, TH can cause re-bleeding post-treatment. This serious complication could partly account for the intermittent protection previously observed. This also raises serious concerns for clinical usage of TH for ICH.
authors.affiliation: 1 Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Shannon
authors.initials: S
authors.lastname: Wowk
authors.affiliation: 2 Department of Biology, MacEwan University, Edmonton, Canada.
authors.forename: Kelly J
authors.initials: KJ
authors.lastname: Fagan
authors.affiliation: 3 Department of Psychology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Yonglie
authors.initials: Y
authors.lastname: Ma
authors.affiliation: 4 Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, Canada.
authors.forename: Helen
authors.initials: H
authors.lastname: Nichol
authors.affiliation: 1 Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada.|3 Department of Psychology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Frederick
authors.initials: F
authors.lastname: Colbourne
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000473:pathology*; D002543:Cerebral Hemorrhage / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D017364:Collagenases; D004195:Disease Models, Animal; D006406:Hematoma / Q000000981:diagnostic imaging / Q000209:etiology*; D007036:Hypothermia, Induced / Q000009:adverse effects* / Q000379:methods; D008297:Male; D017207:Rats, Sprague-Dawley; D017694:Rewarming; D013052:Spectrometry, X-Ray Emission
chemical_list: D017364:Collagenases
keywords: Bleeding; intracerebral hemorrhage; iron; side effects; therapeutic hypothermia