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Comparing platelet function and ultrastructure in smoking and thrombo-embolic ischemic stroke

Dissertation (MSc)--University of Pretoria, 2013.

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Other Authors: Pretorius, Etheresia
Format: Thesis
Language:English
Published: University of Pretoria 2014
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author2 Pretorius, Etheresia
author_browse Pretorius, Etheresia
author_facet Pretorius, Etheresia
collection Thesis
dc_rights_str_mv © 2013 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria.
description Dissertation (MSc)--University of Pretoria, 2013.
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institution University of Pretoria (South Africa)
language English
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spelling oai:repository.up.ac.za:2263/33160 Comparing platelet function and ultrastructure in smoking and thrombo-embolic ischemic stroke Pretorius, Etheresia Du Plooy, Jeanette Noel Stroke Inflammatory Neurological disease Excitotoxicity mechanisms Oxidative damage Apoptosis Ionic imbalances Angiogenesis Neuroprotection Cerebral vessel UCTD Dissertation (MSc)--University of Pretoria, 2013. Stroke is serious neurological disease and is a major cause of death as well as disability throughout the globe. Stroke has a complex pathophysiology that involves inflammatory pathways, excitotoxicity mechanisms, oxidative damage, apoptosis, ionic imbalances, angiogenesis and neuroprotection. 85% of strokes are ischemic and occurs when a cerebral vessel, or any vessel supplying the brain, narrows or loses pressure resulting in subsequent brain ischemia and infarction downstream to the site of obstruction depriving tissues of vital oxygen and nutrients. This may be caused by either atherosclerotic thrombi or distant emboli defined as a mass of clotted blood or other material. It is estimated that over a billion people currently smoke cigarettes or use other tobacco products, seeing as smoking is a major risk factor for stroke this is of major concern. Platelets are hematopoietic cells produced by bone marrow megakaryocytes. Platelets play a role in the development of ischemic stroke primarily by means of their participation in the formation of thromboemboli, the presence of abnormal platelet function may predispose patients to a pro-thrombotic, pro-inflammatory state. The reorganization of the cytoskeleton in platelets is an important factor in the complex mechanisms found in thrombosis and haemostasis. The platelet membrane contains a large number of receptors which specifically bind agonists that stimulate the physiological platelet response. Oxidative stress is one of the mechanisms involved in the neuronal damage of stroke. Oxidative stress is a state of imbalance between free radical production, in particular, reactive oxygen species (ROS), and the ability of the organism to neutralize them, leading to progressive oxidative damage. Smoking is known to result in the generation of various free radicals. Flow cytometric analysis of the platelets of thrombo-embolic ischemic stroke patients and smokers revealed that the membranes of the two groups were altered in some form as well as an increased activation in both groups when compared to healthy individuals. Superoxide levels in the platelets were higher in smokers when compared to stroke patients, while hydrogen peroxide levels were elevated in the platelets of both groups. Superoxide was elevated in the whole blood samples of both groups. The production and subsequent reactions of reactive oxygen species appear to be influential in stroke and smoking and may likely be a crucial factor in the development of a pro-thrombotic, pro-inflammatory state which may prove to be a hallmark in the pathophysiology of stroke and smoking. Confocal microscopy and Scanning electron microscopy showed that platelets of stroke patients and smokers appear to be more activated and more prone to form tight clots. Furthermore an increased amount of superoxide is present in the platelets of stroke patients and smokers, specifically in the centre of clots. This may be an indication that once platelets have aggregated and started to fuse together, the mitochondria are expelled from the platelets and “trapped” within the clot. Atomic force microscopy also indicated both the stroke patients and smoker‟s platelets appear to be in a more activated state than the control group. Here it is apparent that some form of cytoskeletal rearrangement takes place to a more severe extent in the stroke group than in the smokers. Necrosis may be present in the platelets of stroke patients while neither apoptosis nor necrosis can be identified in the platelets of smokers however some form of membrane alteration is likely present. All the techniques used showed an increase in platelet activation in stroke patients and smokers, necrotic platelets may be present in the stroke patients while the platelet membrane of smokers seems to be altered. ROS is present and alters the platelet function of smokers and stroke patients in some way. It appears as if thrombo-embolic ischemic stroke patients and smokers‟ platelets have similar trends in activation but the processes involved to achieve this differ as there are structural differences present. These differences may prove a useful tool to further understand the pathophysiology behind thrombo-embolic ischemic stroke as well as to discover new therapeutic pathways. gm2014 Physiology Unrestricted 2014-01-28T14:26:18Z 2014-01-28T14:26:18Z 2013-09-06 2013 Dissertation Du Plooy, JN 2013, Comparing platelet function and ultrastructure in smoking and thrombo-embolic ischemic stroke, MSc dissertation, University of Pretoria, Pretoria, viewed yymmdd <http://hdl.handle.net/2263/33160> E13/9/939 http://hdl.handle.net/2263/33160 en © 2013 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. application/pdf University of Pretoria
spellingShingle Stroke
Inflammatory
Neurological disease
Excitotoxicity mechanisms
Oxidative damage
Apoptosis
Ionic imbalances
Angiogenesis
Neuroprotection
Cerebral vessel
UCTD
Comparing platelet function and ultrastructure in smoking and thrombo-embolic ischemic stroke
title Comparing platelet function and ultrastructure in smoking and thrombo-embolic ischemic stroke
title_full Comparing platelet function and ultrastructure in smoking and thrombo-embolic ischemic stroke
title_fullStr Comparing platelet function and ultrastructure in smoking and thrombo-embolic ischemic stroke
title_full_unstemmed Comparing platelet function and ultrastructure in smoking and thrombo-embolic ischemic stroke
title_short Comparing platelet function and ultrastructure in smoking and thrombo-embolic ischemic stroke
title_sort comparing platelet function and ultrastructure in smoking and thrombo embolic ischemic stroke
topic Stroke
Inflammatory
Neurological disease
Excitotoxicity mechanisms
Oxidative damage
Apoptosis
Ionic imbalances
Angiogenesis
Neuroprotection
Cerebral vessel
UCTD
url http://hdl.handle.net/2263/33160