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In vitro and in vivo effects of thrombopoietin on protection against hypoxia-ischemia-induced neural damage.

Chiu, Wui Man. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 107-128). / Abstracts in English and Chinese. / Abstract --- p.i / 中文摘要 --- p.iv / Acknowledgements --- p.vi / Publications --- p.viii / Table of Contents --- p.ix / List of Tables --- p.xiv / List of Figures --- p.xv / List of Abbreviations --- p.xviii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Hypoxic-ischemic encephalopathy in human infants --- p.1 / Chapter 1.1.1 --- Incidence --- p.1 / Chapter 1.1.2 --- Biphasic development of HI brain damage --- p.2 / Chapter 1.1.2.1 --- Initiating mechanism: energy failure in immature brain --- p.3 / Chapter 1.1.2.2 --- Biochemical cascades --- p.4 / Chapter 1.1.2.2.1 --- Excitatory amino acid receptor activation by glutamate --- p.4 / Chapter 1.1.2.2.2 --- Intracellular calcium accumulation --- p.4 / Chapter 1.1.2.2.3 --- Formation of free radicals --- p.5 / Chapter 1.1.2.2.3.1 --- Reactive oxygen species (ROS) --- p.5 / Chapter 1.1.2.2.3.2 --- Nitric oxide (NO) --- p.6 / Chapter 1.1.2.3 --- Release of inflammatory mediators --- p.6 / Chapter 1.1.2.4 --- Mitochondrial dysfunction --- p.7 / Chapter 1.1.2.5 --- Final path to death: necrosis or apoptosis --- p.8 / Chapter 1.1.2.6 --- Ways to change: neuronal survival and proliferation signaling --- p.8 / Chapter 1.1.3 --- Interventions for neonatal hypoxia-ischemia --- p.9 / Chapter 1.2 --- Animal models mimicking hypoxia-ischemia brain injury --- p.12 / Chapter 1.2.1 --- Comparisons of animal models of hypoxia-ischemia --- p.12 / Chapter 1.2.2 --- Development of neonatal rat model with hypoxic-ischemic damage --- p.14 / Chapter 1.3 --- Neural stem/progenitor cells --- p.15 / Chapter 1.3.1 --- Effect of hypoxic-ischemia on neural stem/progenitor cells --- p.17 / Chapter 1.4 --- Thrombopoietin --- p.18 / Chapter Chapter 2 --- Objectives --- p.23 / Chapter Chapter 3 --- Materials and Methodology --- p.24 / Chapter 3.1 --- Establishment of neonatal rat model of HI brain damage and effects of TPO on neural protection --- p.24 / Chapter 3.1.1 --- Animal protocols --- p.24 / Chapter 3.1.2 --- Induction of HI brain damage in neonatal rats --- p.24 / Chapter 3.1.3 --- Treatment with TPO --- p.25 / Chapter 3.1.4 --- Sacrifice of rats --- p.25 / Chapter 3.1.5 --- Read-out measurements --- p.26 / Chapter 3.1.5.1 --- Brain weight --- p.26 / Chapter 3.1.5.2 --- Gross injury assessment of the right hemisphere --- p.26 / Chapter 3.1.5.3 --- Histology --- p.27 / Chapter 3.1.5.4 --- Blood cell count --- p.27 / Chapter 3.1.5.6 --- Functional assessments --- p.28 / Chapter 3.1.5.6.1 --- Grip traction test --- p.28 / Chapter 3.1.5.6.2 --- Elevated body swing test --- p.28 / Chapter 3.1.5.7 --- Statistical analysis --- p.28 / Chapter 3.2 --- Establishment of in vitro model of primary mouse NSPs and the effect of TPO on their proliferation --- p.29 / Chapter 3.2.1 --- Mouse embryo dissection for the extraction of NSP --- p.29 / Chapter 3.2.2 --- Culturing of NSP --- p.30 / Chapter 3.2.3 --- Immunofluorescence staining for stem cell markers --- p.31 / Chapter 3.2.4 --- Neurosphere assay with different combinations of mitogens --- p.31 / Chapter 3.2.5 --- Neurosphere assay with different concentrations of TPO --- p.32 / Chapter 3.2.6 --- Neurosphere assay under hypoxia --- p.32 / Chapter 3.2.7 --- Statistical analysis --- p.33 / Chapter Chapter 4 --- Effects of thrombopoietin on neonatal rat models of hypoxia-ischemia brain damage --- p.39 / Chapter 4.1 --- Summary of experimental settings --- p.39 / Chapter 4.2 --- Results --- p.39 / Chapter 4.2.1 --- Mortality --- p.39 / Chapter 4.2.2 --- Effects of TPO on p7 mild damage model 1 week post-surgery --- p.40 / Chapter 4.2.2.1 --- Body and brain weights --- p.40 / Chapter 4.2.2.2 --- Gross injury score --- p.41 / Chapter 4.2.2.3 --- Cortex and hippocampus area --- p.41 / Chapter 4.2.2.4 --- Blood cell counts --- p.42 / Chapter 4.2.3 --- Effects of TPO on p7 severe damage model 1 week post-surgery --- p.43 / Chapter 4.2.3.1 --- Body and brain weights --- p.43 / Chapter 4.2.3.2 --- Gross injury score --- p.43 / Chapter 4.2.3.3 --- Cortex area --- p.44 / Chapter 4.2.3.4 --- Blood cell counts --- p.44 / Chapter 4.2.4 --- Effects of TPO on p7 severe damage model 3 week post-surgery --- p.45 / Chapter 4.2.4.1 --- Body and brain weights --- p.45 / Chapter 4.2.4.2 --- Gross injury score --- p.46 / Chapter 4.2.4.3 --- Blood cell counts --- p.46 / Chapter 4.2.4.4 --- Functional outcomes --- p.46 / Chapter 4.2.5 --- Effects of TPO on pl4 severe damage model 1 week post-surgery --- p.47 / Chapter 4.2.5.1 --- Body and brain weights --- p.47 / Chapter 4.2.5.2 --- Gross injury score --- p.48 / Chapter 4.2.5.3 --- Cortex area --- p.48 / Chapter 4.2.5.4 --- Blood cell counts --- p.49 / Chapter 4.3 --- Discussion --- p.49 / Chapter Chapter 5 --- Effects of thrombopoietin on the proliferation of primary mouse neural stem/ progenitor cells in culture --- p.83 / Chapter 5.1 --- Summary of experimental settings --- p.83 / Chapter 5.2 --- Results --- p.83 / Chapter 5.2.1 --- Effect of EGF or bFGF withdrawal on NSP proliferation --- p.84 / Chapter 5.2.2 --- Dose effect of TPO treatment on NSP proliferation --- p.85 / Chapter 5.2.3 --- Effect of hypoxia --- p.85 / Chapter 5.2.4 --- Effect of TPO treatment in combination with hypoxia --- p.86 / Chapter 5.2.5 --- Detection of neural progenitor cell marker --- p.87 / Chapter 5.3 --- Discussion --- p.88 / Chapter Chapter 6 --- General discussion --- p.101 / Bibliography --- p.106

Identiferoai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_326434
Date January 2008
ContributorsChiu, Wui Man., Chinese University of Hong Kong Graduate School. Division of Medical Sciences.
Source SetsThe Chinese University of Hong Kong
LanguageEnglish, Chinese
Detected LanguageEnglish
TypeText, bibliography
Formatprint, xix, 128 leaves : ill. (some col.) ; 30 cm.
RightsUse of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/)

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