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Desenvolvimento de um novo modelo para o estudo do acidente vascular cerebral perinatal

Bibliographic Details
Main Author: Mendes, Tânia Vanessa Faustino
Publication Date: 2018
Format: Master thesis
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: http://hdl.handle.net/10400.6/8361
Summary: Perinatal stroke is a pathologic condition that occurs between the 20th week of gestation and the 28th day after birth. Despite its incidence being comparable to stroke in adults and being one of the most common causes of hemiplegic cerebral palsy, among other incapacitating symptoms, perinatal stroke remains a poorly studied subject. The evident pathophysiology underlying perinatal stroke is still not well understood, although inflammation and prothrombotic mechanisms seem to have a prevalent role. In this way, the aim of this study was to establish a valid model to study perinatal stroke that would more closely relate to the human pathophysiology. We used oorganotypic hippocampal slice cultures from 2-3-day old mice and then quantified the expression of ionised calcium binding adaptor molecule 1 (a microglia marker), arginase-1 (a M2 microglia marker) and vascular endothelial growth factor receptor, after oxygen and glucose deprivation. The induction of oxygen and glucose deprivation mimics ischaemic conditions. All three molecules were increased after this deprivation, comparing to control (cells not exposed to injury), suggesting that microglia proliferate and adopt a protective phenotype in response to injury. In summary, inflammation seems to be an underlying mechanism in perinatal stroke, as well as microglia seems to be an important mediator. Further investigation is needed in this area in order to better understand the pathophysiology of perinatal stroke and to improve the development of new therapies.
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spelling Desenvolvimento de um novo modelo para o estudo do acidente vascular cerebral perinatalAcidente Vascular Cerebral PerinatalFatias Organotípicas de HipocampoFisiopatologiaIsquemiaMicrogliaPerinatal stroke is a pathologic condition that occurs between the 20th week of gestation and the 28th day after birth. Despite its incidence being comparable to stroke in adults and being one of the most common causes of hemiplegic cerebral palsy, among other incapacitating symptoms, perinatal stroke remains a poorly studied subject. The evident pathophysiology underlying perinatal stroke is still not well understood, although inflammation and prothrombotic mechanisms seem to have a prevalent role. In this way, the aim of this study was to establish a valid model to study perinatal stroke that would more closely relate to the human pathophysiology. We used oorganotypic hippocampal slice cultures from 2-3-day old mice and then quantified the expression of ionised calcium binding adaptor molecule 1 (a microglia marker), arginase-1 (a M2 microglia marker) and vascular endothelial growth factor receptor, after oxygen and glucose deprivation. The induction of oxygen and glucose deprivation mimics ischaemic conditions. All three molecules were increased after this deprivation, comparing to control (cells not exposed to injury), suggesting that microglia proliferate and adopt a protective phenotype in response to injury. In summary, inflammation seems to be an underlying mechanism in perinatal stroke, as well as microglia seems to be an important mediator. Further investigation is needed in this area in order to better understand the pathophysiology of perinatal stroke and to improve the development of new therapies.acidente vascular cerebral perinatal é um evento patológico que ocorre entre a 20ª semana de gestação e o 28º dia após o nascimento. Apesar da sua incidência ser comparável à do acidente vascular cerebral na idade adulta, e de ser uma das causas mais comuns de paralisia cerebral hemiplégica, entre outros sintomas incapacitantes, o acidente vascular cerebral em idade perinatal é um tópico pouco explorado na literatura. A fisiopatologia subjacente não é ainda totalmente compreendida, apesar de mecanismos inflamatórios e pro-trombóticos parecerem ter um papel prevalente. Neste sentido, o objetivo deste estudo foi estabelecer um modelo válido para melhor compreensão do acidente vascular cerebral perinatal, que seja relacionável com a fisiopatologia no humano. Deste modo, foram utilizadas fatias organotípicas de hipocampo de murganhos com 2 a 3 dias de idade, e posteriormente quantificada a expressão de ionised calcium binding adaptor molecule-1 (um marcador da microglia), de arginase-1 (um marcador da microglia M2) e do recetor do fator de crescimento vascular endotelial, após um período de privação de oxigénio e glucose. Esta privação mimetiza in vitro as condições de isquemia. Verificou-se um aumento de todas estas moléculas após privação de oxigénio e glucose, em comparação com o controlo (células não expostas a isquemia), sugerindo um aumento da população microglial e uma resposta protetora por parte destas células face ao dano. Em suma, a inflamação parece ser um mecanismo subjacente ao acidente vascular cerebral perinatal, assim como a microglia parece ser um importante mediador deste processo. No entanto, é necessária mais investigação nesta área, de modo a compreender melhor a fisiopatologia inerente, e deste modo contribuir para o desenvolvimento de novas abordagens terapêuticas.Ferreira, Raquel Margarida da SilvauBibliorumMendes, Tânia Vanessa Faustino2020-01-15T17:06:20Z2018-06-252018-05-102018-06-25T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10400.6/8361urn:tid:202363120enginfo:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-03-11T15:46:47Zoai:ubibliorum.ubi.pt:10400.6/8361Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T01:28:55.530737Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Desenvolvimento de um novo modelo para o estudo do acidente vascular cerebral perinatal
title Desenvolvimento de um novo modelo para o estudo do acidente vascular cerebral perinatal
spellingShingle Desenvolvimento de um novo modelo para o estudo do acidente vascular cerebral perinatal
Mendes, Tânia Vanessa Faustino
Acidente Vascular Cerebral Perinatal
Fatias Organotípicas de Hipocampo
Fisiopatologia
Isquemia
Microglia
title_short Desenvolvimento de um novo modelo para o estudo do acidente vascular cerebral perinatal
title_full Desenvolvimento de um novo modelo para o estudo do acidente vascular cerebral perinatal
title_fullStr Desenvolvimento de um novo modelo para o estudo do acidente vascular cerebral perinatal
title_full_unstemmed Desenvolvimento de um novo modelo para o estudo do acidente vascular cerebral perinatal
title_sort Desenvolvimento de um novo modelo para o estudo do acidente vascular cerebral perinatal
author Mendes, Tânia Vanessa Faustino
author_facet Mendes, Tânia Vanessa Faustino
author_role author
dc.contributor.none.fl_str_mv Ferreira, Raquel Margarida da Silva
uBibliorum
dc.contributor.author.fl_str_mv Mendes, Tânia Vanessa Faustino
dc.subject.por.fl_str_mv Acidente Vascular Cerebral Perinatal
Fatias Organotípicas de Hipocampo
Fisiopatologia
Isquemia
Microglia
topic Acidente Vascular Cerebral Perinatal
Fatias Organotípicas de Hipocampo
Fisiopatologia
Isquemia
Microglia
description Perinatal stroke is a pathologic condition that occurs between the 20th week of gestation and the 28th day after birth. Despite its incidence being comparable to stroke in adults and being one of the most common causes of hemiplegic cerebral palsy, among other incapacitating symptoms, perinatal stroke remains a poorly studied subject. The evident pathophysiology underlying perinatal stroke is still not well understood, although inflammation and prothrombotic mechanisms seem to have a prevalent role. In this way, the aim of this study was to establish a valid model to study perinatal stroke that would more closely relate to the human pathophysiology. We used oorganotypic hippocampal slice cultures from 2-3-day old mice and then quantified the expression of ionised calcium binding adaptor molecule 1 (a microglia marker), arginase-1 (a M2 microglia marker) and vascular endothelial growth factor receptor, after oxygen and glucose deprivation. The induction of oxygen and glucose deprivation mimics ischaemic conditions. All three molecules were increased after this deprivation, comparing to control (cells not exposed to injury), suggesting that microglia proliferate and adopt a protective phenotype in response to injury. In summary, inflammation seems to be an underlying mechanism in perinatal stroke, as well as microglia seems to be an important mediator. Further investigation is needed in this area in order to better understand the pathophysiology of perinatal stroke and to improve the development of new therapies.
publishDate 2018
dc.date.none.fl_str_mv 2018-06-25
2018-05-10
2018-06-25T00:00:00Z
2020-01-15T17:06:20Z
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