The study of glial scar formation after brain ischemia using in-vitro strategies

Reactive gliosis is a generic response to Central Nervous System (CNS) injury mediated by astrocytes and microglia. Following ischemic damage to the CNS parenchyma, the injured area becomes surrounded by a dense astroglial cell layer known as glial scar. Glial scar formation has been recognized for...

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Autor principal: Mannava, Raja Sekhar
Otros Autores: Mertelsmann, Roland
Formato: Tesis de maestría acceptedVersion
Lenguaje:Inglés
Publicado: Facultad de Farmacia y Bioquímica 2015
Materias:
Cicatriz glial
Isquemia cerebral
In-vitro
Brain ischemia
In vitro
Glial scar
Ciencia de la vida
Acceso en línea:http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_834
http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_834.dir/834.PDF
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Repositorio Digital de la Universidad de Buenos Aires (UBA) de Universidad de Buenos Aires
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record_format dspace
spelling I28-R145-HWA_8342019-09-27 Reactive gliosis is a generic response to Central Nervous System (CNS) injury mediated by astrocytes and microglia. Following ischemic damage to the CNS parenchyma, the injured area becomes surrounded by a dense astroglial cell layer known as glial scar. Glial scar formation has been recognized for many decades as a major impediment for neuronal reconnection and a serious obstacle for functional recovery. However, more recent studies have shown that scar limits the area of damage, preventing the diffusion of blood-derived activated immune cells into the CNS that could cause a generalized proinflammatory-neurodegenerative response.\nIn spite that it has been morphologically recognized for many years since Ramon y Cajal times, to study the biochemical signaling cascades involved in glial scar formation has been difficult mostly because of the in vivo nature of the process.\nIn this context, we studied here the mechanisms of glial scar assembly/disassembly in vitro to identify potential pharmacological targets for therapeutic interventions. To achieve this goal we will use the classical 2-Dimensional (2D) astroglial cultures, but we will also develop 3-dimensional (3D) astroglial cultures by using nanotube matrixes to attempt to better reproduce the in vivo situation. The results of this thesis showed that meningeal macrophages or ischemia-activated macrophages induce astroglial retraction and formation of scar-like structures in vitro. Scar-forming astrocytes over-express GFAP, S100B and TLR2-4. Using the NF-?B antagonist BAY-11-7082 we demonstrated that scar formation and its density is partially NF-?B dependent. Finally, in 3D astroglial culture grown on hydromatrix nanotubes, we showed that DAMPs can induce astroglial polarization but not the formation of the glial scar in vitro. We conclude that TLR/ NF-?B pathway is probably implicated in the glial scar formation or stabilization and that DAMPs and macrophages are necessary for the formation of glial scars in vitro. Fil: Mannava, Raja Sekhar. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Mertelsmann, Roland Murta, Verónica Facultad de Farmacia y Bioquímica Ramos, Alberto Javier Mannava, Raja Sekhar 2015-06-01 application/pdf Rosenstein, Ruth Garcia, Corina Borner, Christoph Cicatriz glial Isquemia cerebral In-vitro Brain ischemia In vitro Glial scar eng Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/2.5/ar/ Ciencia de la vida The study of glial scar formation after brain ischemia using in-vitro strategies info:eu-repo/semantics/masterThesis info:ar-repo/semantics/tesis de maestría info:eu-repo/semantics/acceptedVersion http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_834 http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_834.dir/834.PDF
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-145
collection Repositorio Digital de la Universidad de Buenos Aires (UBA)
language Inglés
orig_language_str_mv eng
topic Cicatriz glial
Isquemia cerebral
In-vitro
Brain ischemia
In vitro
Glial scar
Ciencia de la vida
spellingShingle Cicatriz glial
Isquemia cerebral
In-vitro
Brain ischemia
In vitro
Glial scar
Ciencia de la vida
Mannava, Raja Sekhar
The study of glial scar formation after brain ischemia using in-vitro strategies
topic_facet Cicatriz glial
Isquemia cerebral
In-vitro
Brain ischemia
In vitro
Glial scar
Ciencia de la vida
description Reactive gliosis is a generic response to Central Nervous System (CNS) injury mediated by astrocytes and microglia. Following ischemic damage to the CNS parenchyma, the injured area becomes surrounded by a dense astroglial cell layer known as glial scar. Glial scar formation has been recognized for many decades as a major impediment for neuronal reconnection and a serious obstacle for functional recovery. However, more recent studies have shown that scar limits the area of damage, preventing the diffusion of blood-derived activated immune cells into the CNS that could cause a generalized proinflammatory-neurodegenerative response.\nIn spite that it has been morphologically recognized for many years since Ramon y Cajal times, to study the biochemical signaling cascades involved in glial scar formation has been difficult mostly because of the in vivo nature of the process.\nIn this context, we studied here the mechanisms of glial scar assembly/disassembly in vitro to identify potential pharmacological targets for therapeutic interventions. To achieve this goal we will use the classical 2-Dimensional (2D) astroglial cultures, but we will also develop 3-dimensional (3D) astroglial cultures by using nanotube matrixes to attempt to better reproduce the in vivo situation. The results of this thesis showed that meningeal macrophages or ischemia-activated macrophages induce astroglial retraction and formation of scar-like structures in vitro. Scar-forming astrocytes over-express GFAP, S100B and TLR2-4. Using the NF-?B antagonist BAY-11-7082 we demonstrated that scar formation and its density is partially NF-?B dependent. Finally, in 3D astroglial culture grown on hydromatrix nanotubes, we showed that DAMPs can induce astroglial polarization but not the formation of the glial scar in vitro. We conclude that TLR/ NF-?B pathway is probably implicated in the glial scar formation or stabilization and that DAMPs and macrophages are necessary for the formation of glial scars in vitro.
author2 Mertelsmann, Roland
author_facet Mertelsmann, Roland
Mannava, Raja Sekhar
format Tesis de maestría
Tesis de maestría
acceptedVersion
author Mannava, Raja Sekhar
author_sort Mannava, Raja Sekhar
title The study of glial scar formation after brain ischemia using in-vitro strategies
title_short The study of glial scar formation after brain ischemia using in-vitro strategies
title_full The study of glial scar formation after brain ischemia using in-vitro strategies
title_fullStr The study of glial scar formation after brain ischemia using in-vitro strategies
title_full_unstemmed The study of glial scar formation after brain ischemia using in-vitro strategies
title_sort study of glial scar formation after brain ischemia using in-vitro strategies
publisher Facultad de Farmacia y Bioquímica
publishDate 2015
url http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_834
http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_834.dir/834.PDF
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