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Permanent link (DOI): https://doi.org/10.7939/R3RH5R

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Mechanisms of injury and recovery after an intracerebral hemorrhage Open Access

Descriptions

Other title
Subject/Keyword
Thrombin
Intracerebral hemorrhage
Rehabilitation
Bipyridine
Iron toxicity
Stroke
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Caliaperumal, Jayalakshmi
Supervisor and department
Frederick Colbourne (Psychology and Centre for Neuroscience)
Examining committee member and department
Dickson, Clayton T (Psychology and Centre for Neuroscience)
Kerr, Bradley J (Pharmacology and Centre for Neuroscience)
Winship, Ian R (Psychiatry and Centre for Neuroscience)
Treit, Dallas (Psychology and Centre for Neuroscience)
Metz, Gerlinde A (Department of Neuroscience)
Department
Centre for Neuroscience
Specialization

Date accepted
2013-11-14T14:47:43Z
Graduation date
2014-06
Degree
Doctor of Philosophy
Degree level
Doctoral
Abstract
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.
Language
English
DOI
doi:10.7939/R3RH5R
Rights
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
Citation for previous publication
Caliaperumal, J., et al. (2012). "Intra-parenchymal ferrous iron infusion causes neuronal atrophy, cell death and progressive tissue loss: implications for intracerebral hemorrhage." Exp Neurol 15: 363-369.Caliaperumal, J., et al. (2013). "Bipyridine, an Iron Chelator, Does Not Lessen Intracerebral Iron-Induced Damage or Improve Outcome After Intracerebral Hemorrhagic Stroke in Rats." Translational Stroke Research: 1-10. DOI 10.1007/s12975-013-0272-3

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