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Effects of oestrogen on the neural tissue, thrombotic and inflammatory profiles of rats in transient experimental cerebral ischaemia

Thesis (PhD)--University of Pretoria, 2013.

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Other Authors: Pretorius, Etheresia
Format: Thesis
Language:English
Published: University of Pretoria 2013
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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 Thesis (PhD)--University of Pretoria, 2013.
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institution University of Pretoria (South Africa)
language English
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publisher University of Pretoria
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spelling oai:repository.up.ac.za:2263/32809 Effects of oestrogen on the neural tissue, thrombotic and inflammatory profiles of rats in transient experimental cerebral ischaemia Pretorius, Etheresia Van der Spuy, Wendy Jeannette wendyvds@gmail.com Bosman, Marius C. Van der Spuy, Wendy Jeannette Van der Spuy, Wendy Jeannette Disability Oestrogen Cerebral ischaemia Blood-brain barrier disruption Inflammation Thrombosis UCTD Estrogen Thesis (PhD)--University of Pretoria, 2013. Cerebral ischaemia by mechanism of thrombosis is one of the leading causes of disability and/or death worldwide, the outcome thereof increasing in severity with advancing age. Cerebral ischaemia triggers a cascade of events including inflammation, blood-brain barrier disruption and apoptosis. It is well known that oestrogen is neuroprotective through various mechanisms including the interruption of inflammation, regulation of thrombosis and delay of apoptosis. This creates a strong factorial interconnection in predicting the consequences of cerebral ischaemia. Since platelets have a central role in thrombosis and inflammation, their ultrastructure being altered in conditions of inflammatory and thrombotic derivation, the question arises whether chemical analysis of coagulation factors and ultrastructural analyses of platelet morphology may provide further insight into the role of oestrogen during ischaemic insult associated with stroke. Accordingly, an exclusively hyperglycaemic modification of the two-vessel occlusion model for inducing experimental cerebral ischaemia was established, since pre-ischaemic hyperglycaemia is known to intensify the outcome of cerebral ischaemic injury. Consequent neural tissue injury levels were correlated for three experimental groups (males, cyclic and acyclic females) of Sprague Dawley rats at vital times, to the presence of oestrogen as well as changes in coagulation factors and ultrastructure. This design allowed for an association to be formed between cerebral ischaemia, inflammation and thrombotic potential. Collectively the results strongly suggest that oestrogen is indeed neuroprotective through various actions including roles in the regulation of thrombosis and inflammation, targeting neural cells through the inhibition of apoptosis and exerting anti-inflammatory and antioxidant effects. It is evident that under the influence of oestrogen in cyclic females, there is reduced neural tissue injury as well as a lesser degree of inflammation evident in coagulation factor analysis and platelet activation morphology when compared to males and acyclic females. Oestrogen therefore exerts positive effects on the outcome of cerebral ischaemia through mechanisms which regulate inflammation, thrombosis and apoptosis. Furthermore it is unmistakeable that neural injury is closely shadowed, if not preceded, by inflammatory changes in the coagulation system, particularly manifested in platelet ultrastructure. It is therefore suggested that platelets may be used successfully to follow the progression of events of cerebral ischaemia and possibly assist in the assessment of treatment strategies and their effects on haemostasis. This research advances the understanding that inflammation is evident soon after ischaemic insult and if such inflammation is not curbed, necrosis of platelets and more severe injury to neural tissue may follow. Therefore, the development of agents which not only target thrombosis, but also which control inflammation must be explored to advance treatment strategies. It is proposed that even before it is determined whether a stroke has been caused by thromboembolism or haemorrhage; it will be beneficial to immediately target inflammation in order to prevent most severe consequences in human patients. gm2013 Anatomy unrestricted 2013-12-10T08:46:26Z 2013-12-10T08:46:26Z 2013-09-06 2013-12-09 Thesis Van der Spuy, W.J. 2013, Effects of oestrogen on the neural tissue, thrombotic and inflammatory profiles of rats in transient experimental cerebral ischaemia, PhD thesis, University of Pretoria, Pretoria, viewed yymmdd <http://hdl.handle.net/2263/32809> D13/9/970/gm http://hdl.handle.net/2263/32809 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 Disability
Oestrogen
Cerebral ischaemia
Blood-brain barrier disruption
Inflammation
Thrombosis
UCTD
Estrogen
Effects of oestrogen on the neural tissue, thrombotic and inflammatory profiles of rats in transient experimental cerebral ischaemia
title Effects of oestrogen on the neural tissue, thrombotic and inflammatory profiles of rats in transient experimental cerebral ischaemia
title_full Effects of oestrogen on the neural tissue, thrombotic and inflammatory profiles of rats in transient experimental cerebral ischaemia
title_fullStr Effects of oestrogen on the neural tissue, thrombotic and inflammatory profiles of rats in transient experimental cerebral ischaemia
title_full_unstemmed Effects of oestrogen on the neural tissue, thrombotic and inflammatory profiles of rats in transient experimental cerebral ischaemia
title_short Effects of oestrogen on the neural tissue, thrombotic and inflammatory profiles of rats in transient experimental cerebral ischaemia
title_sort effects of oestrogen on the neural tissue thrombotic and inflammatory profiles of rats in transient experimental cerebral ischaemia
topic Disability
Oestrogen
Cerebral ischaemia
Blood-brain barrier disruption
Inflammation
Thrombosis
UCTD
Estrogen
url http://hdl.handle.net/2263/32809