Mechanisms of injury and recovery after an intracerebral hemorrhage

  • Author / Creator
    Caliaperumal, Jayalakshmi
  • Bleeding within the brain parenchyma causes a severe form of stroke named intracerebral hemorrhagic stroke (ICH). An understanding of how brain injury occurs after an ICH may suggest alternative therapies. For this reason, the current dissertation focuses on two important questions of how the brain injury and recovery occurs after ICH. In these experiments we studied the 2 putative mechanisms of injury, thrombin and iron. Moreover we also evaluated whether recovery after ICH occurs by ameliorating iron toxicity. Chapter 2 assesses the role of thrombin by injecting thrombin directly into the rat striatum. After thrombin was given, the surviving neurons were scrutinized in the peri-infarct region using Golgi-Cox stain. We also assessed the short and long term effects of thrombin in causing tissue loss. Even a small dose of thrombin caused surviving neurons to atrophy; however thrombin did not cause long-term tissue loss. In chapter 3 a similar experimental method was employed to evaluate the role of iron. Iron caused remarkable neuronal atrophy, short and long term tissue loss and neurodegeneration. Furthermore, to attenuate the toxicity of iron, we administered a ferrous iron chelator (bipyridine) in three different models of ICH (collagenase, whole blood and ferrous chloride model) with multiple behavioural testing (neurological score, walking and turning bias) and histological endpoints (tissue loss, neurodegeneration, chapter 4). Despite testing the drug with multiple models and end points we could not find any beneficial effect of bipyridine in ameliorating iron toxicity. The experiments described in chapter 5 aimed to address the mechanism by which rehabilitation promotes functional recovery after an ICH. Skilled reaching therapy combined with enriched environment was given as rehabilitation treatments after ICH induced by collagenase. Rehabilitation promoted behavioural recovery and showed a neuroprotective effect by reducing neurodegeneration (Fluoro-Jade stained cells), but did not influence the iron toxicity and inflammation after ICH. In summary, our results suggest that thrombin contributes to an acute phase of injury and iron causes both acute and chronic injury after ICH. The data also suggest that rehabilitation therapy improves functional recovery and neuroprotection without influencing iron toxicity and inflammation.

  • 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)
    • Frederick Colbourne (Psychology and Centre for Neuroscience)
  • Examining committee members and their departments
    • Treit, Dallas (Psychology and Centre for Neuroscience)
    • Kerr, Bradley J (Pharmacology and Centre for Neuroscience)
    • Dickson, Clayton T (Psychology and Centre for Neuroscience)
    • Metz, Gerlinde A (Department of Neuroscience)
    • Winship, Ian R (Psychiatry and Centre for Neuroscience)