Delayed hypothermia following permanent focal ischemia: influence of method and duration

  • Author / Creator
    Clark, Darren
  • Stroke is a leading cause of disability in Canada. Delayed hypothermia improves outcome in patients following cardiac arrest and reduces lesion volume in rodents after transient focal ischemia, but less is known about the effectiveness of delayed hypothermia following permanent focal ischemia. In Chapter 1, the efficacy of 12, 24 or 48 h of delayed hypothermia was evaluated one week following pMCAO. All treatments attenuated neurological deficits and brain water content, but only the 24 and 48 h treatments reduced stepping error rate and lesion volume. Thus, delayed hypothermia attenuates brain injury and functional deficits following permanent middle cerebral artery occlusion (pMCAO). Longer bouts of cooling provide superior protection; an effect that is not explained by lessened edema. Chapter 3 describes a novel method of focal brain hypothermia in rats. A metal coil was implanted between the Temporalis muscle and adjacent skull and flushed with cold water. Focal, ipsilateral cooling was successfully produced without cooling of the opposite hemisphere or the core. One day of focal hypothermia was maintained in awake rats without significant alterations in blood pressure, heart rate or body temperature. The described simple method allows for safe inductions of focal brain hypothermia in anesthetized or conscious rats, and is ideally suited to trauma or stroke studies. In Chapter 4, long-term efficacy of 12 and 48 h of delayed focal or systemic hypothermia was evaluated following pMCAO. Both systemic treatments equally reduced lesion volume and skilled reaching deficits compared to normothermic controls, but only the 48 h treatment reduced neurological deficits. Conversely, 12 h of focal cooling did not significantly improve outcome, whereas 48 h of focal brain cooling attenuated functional deficits and reduced lesion volume. Thus, both delayed focal and systemic hypothermia attenuate long-term brain injury and functional deficits following pMCAO. Duration of cooling is clearly an important factor that may depend upon the method of cooling. Overall, this data indicates that delayed and prolonged hypothermia provides substantial and persistent protection against pMCAO in the rat. Prolonged hypothermia is a promising neuroprotective therapy for acute stroke and further clinical investigation is warranted.

  • Subjects / Keywords
  • Graduation date
  • Type of Item
  • Degree
    Doctor of Philosophy
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  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
    • Centre for Neuroscience
  • Supervisor / co-supervisor and their department(s)
    • Colbourne, Fred (Psychology)
  • Examining committee members and their departments
    • Caplan, Jeremy (Psychology)
    • Treit, Dallas (Psychology)
    • Pittman, Quentin (Physiology and Biophysics)
    • Krukoff, Teresa (Cell Biology)