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Summary: Mammalian neurons exhibit extreme sensitivity to oxygen deprivation and undergo rapid and irreversible degeneration when oxygen supply is curtailed. Though several neuroprotective pathways are activated during oxygen deprivation, their analyses are masked by the complex series of pathological events which are triggered simultaneously. Such events can be analyzed in the anoxia tolerant fresh water turtle, which can inherently survive the conditions of oxygen deprivation and post-anoxic reoxygenation without brain damage. It is likely in such a model that modulation of a particular molecular pathway is adaptive rather than pathological. The major objective behind this study was to analyze the intracellular signaling pathways mediating the protective effects of adenosine, a potential neuromodulator, and its effect on cell survival by influencing the key prosurvival proteins that prevent apoptosis. In vivo and in vitro studies have shown that adenosine acts as a neuroprotective metabolite and its action can be duplicated or abrogated using specific agonist and antagonists. Stimulating the adenosine receptors using selective A1 receptor agonist N6-cyclopentyladenosine (CPA) activated the presumed prosurvival ERK and P13-K/AKT cascade promoting cell survival, and suppression of the receptor using the selective antagonist DPCPX (8- cyclopentyl-1,3-dipropylxanthine) activated the prodeath JNK and P38 pathways. The complex regulation of the MAPK's/AKT signaling cascades was also analyzed using their specific inhibitors. The inhibiton of the ERK and AKT pathway increased cell death, indicating a prosurvival role, whereas inhibiton of the JNK and p38 pathway increased cell survival in this model. In vitro studies have also shown a high Bcl-2/BAX ratio during anoxia and reoxygenation, indicating a strong resistance to cell death via apoptosis., Summary: Silencing of the anti-apoptotic Bcl-2 gene using specific siRNA upregulated levels of prodeath BAX, thus altering the Bcl-2/BAX ratio and elevating cleaved Caspase-3 levels leading to increased cell death. Another promising neuroprotective target which we analyzed was Neuroglobin, which was induced during oxygen crisis and silencing this gene indicated that its plays a major role in modulation of ROS. This study strongly emphasizes the advantages of an alternate animal model in elucidating neuroprotective mechanisms and revealing novel therapeutic targets which could eventually help clinicians to design new stroke therapies based on naturally tolerant organisms., by Gauri Nayak., Thesis (Ph.D.)--Florida Atlantic University, 2009., Includes bibliography., Electronic reproduction. Boca Raton, Fla., 2009. Mode of access: World Wide Web.

Wong Lai Lok., Thesis (M.Phil.)--Chinese University of Hong Kong, 2005., Includes bibliographical references (leaves 162-173)., s in English and Chinese., p.ii, Acknowledgements --- p.vi, Publications --- p.vii, Abbreviations --- p.viii, Chapter Chapter 1 --- Introduction --- p.1, Chapter 1.1. --- Historical Background --- p.2, Chapter 1.2. --- Heterogeneity of mast cells --- p.3, Chapter 1.3. --- Mast cell mediators --- p.5, Chapter 1.3.1. --- Performed and granule associated mediators --- p.5, Chapter 1.3.2. --- Newly synthesized mediators --- p.8, Chapter 1.3.3. --- Cytokines --- p.10, Chapter 1.4. --- Mast cell activation --- p.10, Chapter 1.4.1. --- Aggregation of IgE Receptors (FcεRI) --- p.10, Chapter 1.4.2. --- Activation of Phospholipase C --- p.11, Chapter 1.4.3. --- Activation of Adenylate cyclase --- p.13, Chapter 1.5. --- Adenosine --- p.14, Chapter 1.5.1. --- Adenosine receptors --- p.14, Chapter 1.5.2. --- Selective agonists and antagonists --- p.17, Chapter 1.5.3. --- Physiological and pathological roles of adenosine --- p.20, Chapter 1.6. --- Role of adenosine receptors in mast cell activation --- p.21, Chapter 1.7. --- Aims of the study --- p.23, Chapter Chapter 2 --- Materials and Methods --- p.30, Chapter 2.1. --- Materials --- p.31, Chapter 2.1.1. --- Mast cells secretagogues --- p.31, Chapter 2.1.2. --- Anti-allergic compounds --- p.31, Chapter 2.1.3. --- Adenosine receptor agonists and antagonists --- p.31, Chapter 2.1.4. --- Materials for buffers --- p.32, Chapter 2.1.5. --- Materials for rat sensitization --- p.32, Chapter 2.1.6. --- Materials for histamine assay --- p.33, Chapter 2.1.7. --- Miscellaneous --- p.33, Chapter 2.2. --- Buffers and stock solutions --- p.34, Chapter 2.2.1 --- Buffer ingredients --- p.34, Chapter 2.2.2 --- Stock solutions --- p.34, Chapter 2.3. --- Source of mast cells --- p.35, Chapter 2.3.1. --- Animals --- p.35, Chapter 2.3.2. --- Sensitization of animals --- p.35, Chapter 2.3.3. --- Isolation of rat peritoneal mast cells --- p.35, Chapter 2.3.4. --- Mast cells purification --- p.36, Chapter 2.3.5. --- Cell counting --- p.36, Chapter 2.4. --- General protocol for histamine release --- p.37, Chapter 2.4.1. --- Histamine assay --- p.37, Chapter 2.4.2. --- Antagonist studies --- p.38, Chapter 2.4.3. --- Determination of histamine contents --- p.38, Chapter 2.4.4. --- Calculation of histamine levels --- p.39, Chapter 2.5. --- Statistical analysis --- p.40, Chapter Chapter 3 --- "Effects of adenosine, adenosine deaminase and adenosine receptor agonists on mast cell activation" --- p.42, Chapter 3.1. --- Introduction --- p.43, Chapter 3.2. --- Materials and methods --- p.44, Chapter 3.3. --- Results --- p.45, Chapter 3.3.1. --- Effects of adenosine on anti-IgE induced histamine release in HEPES buffer --- p.45, Chapter 3.3.2. --- Effects of NECA on anti-IgE induced histamine release in HEPES buffer --- p.46, Chapter 3.3.3. --- Effects of CCPA on anti-IgE induced histamine release in HEPES buffer --- p.47, Chapter 3.3.4. --- Effects of CPA on anti-IgE induced histamine release in HEPES buffer --- p.47, Chapter 3.3.5. --- Effects of CGS21680 on anti-IgE induced histamine release in HEPES buffer --- p.48, Chapter 3.3.6. --- Effects of Cl-MECA on anti-IgE induced histamine release in HEPES buffer --- p.49, Chapter 3.3.7. --- Effects of adenosine deaminase on anti-IgE induced histamine release from rat peritoneal mast cells --- p.50, Chapter 3.3.8. --- Effects of NECA on anti-IgE induced histamine release with and without adenosine deaminase --- p.50, Chapter 3.3.9. --- Effects of Cl-MECA on anti-IgE induced histamine release with and without adenosine deaminase --- p.53, Chapter 3.3.10. --- Effects of CV1808 on anti-IgE induced histamine release in HEPES buffer --- p.55, Chapter 3.4. --- Discussion --- p.76, Chapter 3.5. --- Conclusion --- p.83, Chapter Chapter 4 --- Effects of adenosine receptor antagonists on mast cell activation --- p.88, Chapter 4.1. --- Introduction --- p.89, Chapter 4.2. --- Materials and methods --- p.90, Chapter 4.3. --- Results --- p.91, Chapter 4.3.1. --- Effects of A1 receptor antagonist DPCPX on modulations of anti-IgE induced histamine release by adenosine receptor agonists --- p.91, Chapter 4.3.2. --- Effects of A2A receptor antagonist ZM241385 on modulations of anti-IgE induced histamine release by adenosine receptor agonists --- p.91, Chapter 4.3.3. --- Effects of A2B receptor antagonist MRS 1706 on modulations of anti-IgE induced histamine release by adenosine receptor agonists --- p.92, Chapter 4.3.4. --- Effects of A3 receptor antagonist VUF5574 on modulations of anti-IgE induced histamine release by adenosine receptor agonists --- p.93, Chapter 4.3.5. --- Further characterization of adenosine mediated potentiation of anti-IgE histamine release using VUF5574 and ZM241385 --- p.93, Chapter 4.3.6. --- Effects of theophylline on anti-IgE induced percentage potentiation in HEPES buffer --- p.95, Chapter 4.4. --- Discussion --- p.130, Chapter 4.5. --- Conclusion --- p.135, Chapter Chapter 5 --- Further characterization of the effects of adenosine on mast cells --- p.138, Chapter 5.1. --- Introduction --- p.139, Chapter 5.2. --- Materials and methods --- p.141, Chapter 5.3. --- Results --- p.142, Chapter 5.3.1. --- Effects of anti-IgE induced histamine release in calcium free and HEPES buffers --- p.142, Chapter 5.3.2. --- Effects of adenosine on anti-IgE induced histamine release in calcium free buffer --- p.143, Chapter 5.3.3. --- Effects of adenosine deaminase on compound48/80 induced histamine release from rat peritoneal mast cells --- p.143, Chapter 5.3.4. --- Effects of adenosine on compound 48/80 induced histamine release in HEPES buffer --- p.144, Chapter 5.3.5. --- Effects of adenosine deaminase on A23187 induced histamine release from rat peritoneal mast cells --- p.144, Chapter 5.3.6. --- Effects of adenosine on calcium ionophore A23187 induced histamine release in HEPES buffer --- p.145, Chapter 5.3.7. --- Effects of adenosine receptor antagonists on inosine mediated enhancement of anti-IgE induced histamine release --- p.145, Chapter 5.4. --- Discussion --- p.157, Chapter 5.5. --- Conclusion --- p.160, References --- p.162, http://library.cuhk.edu.hk/record=b5892472, Use 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/)