Influence of therapeutic hypothermia on neuroprotection and post-ischemic plasticity in a rat model of global ischemia

  • Author / Creator
    Silasi, Gergely
  • Blood flow to the brain may be disrupted by either a stroke (such as focal ischemia or hemorrhage) or cardiac arrest, where the whole brain becomes ischemic. Both forms of injury result in irreversible neuronal loss leading to neurological impairments and a decrease in the quality of life. Neuroprotective treatments are aimed at minimizing the damage that occurs after brain ischemia, and one of the most successful neuroprotectants developed so far is therapeutic hypothermia. Prolonged cooling has been shown to prevent CA1 neuronal death in animal models of global ischemia and the treatment also improves survival and neurological function in patients resuscitated from cardiac arrest. In contrast to the well know neuroprotective properties of hypothermia, the effect of this treatment on post-ischemic plasticity and reorganization has not been clearly investigated. This is an important issue, as plastic changes in remaining brain circuits facilitate functional improvement and recovery after ischemia. The current thesis evaluated the influence of hypothermia on several forms of post-ischemic plasticity including neurogenesis and growth factor expression in the hippocampus. A rat model of global ischemia was used to induce degeneration of hippocampal CA1 neurons, and hypothermia was applied either systemically (whole body cooling) or through unilateral brain cooling. We found that the treatment did not negatively impact post-ischemic plasticity on any of our measures even when cooling was maintained for up to 7 days. These results suggest that prolonged cooling may be a safe treatment, however additional models of ischemia should be used to assess this in future studies.

  • Subjects / Keywords
  • Graduation date
    Fall 2011
  • Type of Item
  • Degree
    Doctor of Philosophy
  • DOI
  • 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
  • Supervisor / co-supervisor and their department(s)
  • Examining committee members and their departments
    • Winship, Ian (Psychiatry)
    • Treit, Dallas (Psychology)
    • Walz, Wolfgang (Psychiatry)
    • Fouad, Karim (Rehab Medicine)