Gliogenesis from the subventricular zone modulates the extracellular matrix at the glial scar after brain ischemia
Activation of the subventricular zone (SVZ) following cerebral ischemia is one of the brain’s early responses to counteract neuron loss and minimize tissue damage. Impaired brain regions communicate with the SVZ through various chemotactic signals that promote cell migration and differentiation, pri...
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eLife Sciences Publications Ltd
2025-08-01
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| Online Access: | https://elifesciences.org/articles/96076 |
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| author | Maria Ardaya Marie-Catherine Tiveron Harold Cremer Esther Rubio-López Abraham Martín Benjamin Dehay Fernando Pérez-Cerdá Carlos Matute Federico N Soria Fabio Cavaliere |
| author_facet | Maria Ardaya Marie-Catherine Tiveron Harold Cremer Esther Rubio-López Abraham Martín Benjamin Dehay Fernando Pérez-Cerdá Carlos Matute Federico N Soria Fabio Cavaliere |
| author_sort | Maria Ardaya |
| collection | DOAJ |
| description | Activation of the subventricular zone (SVZ) following cerebral ischemia is one of the brain’s early responses to counteract neuron loss and minimize tissue damage. Impaired brain regions communicate with the SVZ through various chemotactic signals that promote cell migration and differentiation, primarily involving neural stem cells, neuroblasts, or glioblasts. However, the activation of gliogenesis and the role of newly formed astrocytes in the post-ischemic scenario remain subjects of debate. We have previously demonstrated that adenosine release after brain ischemia prompts the SVZ to generate new astrocytes. Here, we used transient brain ischemia in mice to identify the cellular origin of these astrocytes within the SVZ neurogenic niche and investigate their role in the pathological process. By combining immunofluorescence, BrdU-tracing, and genetic cell labeling, we tracked the migration of newborn astrocytes, positive for the proteoglycan marker Thbs4, from the dorsal and medial SVZ to the perilesional barrier surrounding the ischemic core, known as the ‘glial scar’. We found that these Thbs4-positive astrocytes modulate the dense extracellular matrix at the lesion border by both synthesizing and degrading hyaluronan. We also show that while the accumulation of hyaluronan at the lesion site is sufficient to recruit newborn astrocytes, its degradation at the SVZ correlates with gliogenesis. These findings suggest that newborn astrocytes could be a promising pharmacological target for modulating the glial scar after brain ischemia and facilitating tissue regeneration. |
| format | Article |
| id | doaj-art-645c628c8d054c8bb82ea47efbce77e9 |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | eLife Sciences Publications Ltd |
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| spelling | doaj-art-645c628c8d054c8bb82ea47efbce77e92025-08-20T03:47:17ZengeLife Sciences Publications LtdeLife2050-084X2025-08-011310.7554/eLife.96076Gliogenesis from the subventricular zone modulates the extracellular matrix at the glial scar after brain ischemiaMaria Ardaya0https://orcid.org/0000-0002-0103-5649Marie-Catherine Tiveron1Harold Cremer2https://orcid.org/0000-0002-8673-5176Esther Rubio-López3Abraham Martín4Benjamin Dehay5https://orcid.org/0000-0003-1723-9045Fernando Pérez-Cerdá6Carlos Matute7https://orcid.org/0000-0001-8672-711XFederico N Soria8https://orcid.org/0000-0003-1229-9663Fabio Cavaliere9https://orcid.org/0000-0003-2003-522XAchucarro Basque Center for Neuroscience, Leioa, Spain; Department of Neuroscience, University of the Basque Country (UPV/EHU), Leioa, Spain; CIBERNED, Madrid, SpainAix Marseille University, CNRS, IBDM, Campus de Luminy, Marseille, FranceAix Marseille University, CNRS, IBDM, Campus de Luminy, Marseille, FranceAchucarro Basque Center for Neuroscience, Leioa, Spain; CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), San Sebastian, SpainAchucarro Basque Center for Neuroscience, Leioa, Spain; Ikerbasque, Basque Foundation for Science, Bilbao, SpainUniversity of Bordeaux, CNRS, IMN, UMR 5293, Bordeaux, FranceAchucarro Basque Center for Neuroscience, Leioa, Spain; Department of Neuroscience, University of the Basque Country (UPV/EHU), Leioa, Spain; CIBERNED, Madrid, SpainAchucarro Basque Center for Neuroscience, Leioa, Spain; Department of Neuroscience, University of the Basque Country (UPV/EHU), Leioa, Spain; CIBERNED, Madrid, SpainAchucarro Basque Center for Neuroscience, Leioa, Spain; Department of Neuroscience, University of the Basque Country (UPV/EHU), Leioa, Spain; CIBERNED, Madrid, Spain; Ikerbasque, Basque Foundation for Science, Bilbao, SpainAchucarro Basque Center for Neuroscience, Leioa, Spain; Department of Neuroscience, University of the Basque Country (UPV/EHU), Leioa, Spain; CIBERNED, Madrid, Spain; Basque Biomodel Platform for Human Research (BBioH), Leioa, SpainActivation of the subventricular zone (SVZ) following cerebral ischemia is one of the brain’s early responses to counteract neuron loss and minimize tissue damage. Impaired brain regions communicate with the SVZ through various chemotactic signals that promote cell migration and differentiation, primarily involving neural stem cells, neuroblasts, or glioblasts. However, the activation of gliogenesis and the role of newly formed astrocytes in the post-ischemic scenario remain subjects of debate. We have previously demonstrated that adenosine release after brain ischemia prompts the SVZ to generate new astrocytes. Here, we used transient brain ischemia in mice to identify the cellular origin of these astrocytes within the SVZ neurogenic niche and investigate their role in the pathological process. By combining immunofluorescence, BrdU-tracing, and genetic cell labeling, we tracked the migration of newborn astrocytes, positive for the proteoglycan marker Thbs4, from the dorsal and medial SVZ to the perilesional barrier surrounding the ischemic core, known as the ‘glial scar’. We found that these Thbs4-positive astrocytes modulate the dense extracellular matrix at the lesion border by both synthesizing and degrading hyaluronan. We also show that while the accumulation of hyaluronan at the lesion site is sufficient to recruit newborn astrocytes, its degradation at the SVZ correlates with gliogenesis. These findings suggest that newborn astrocytes could be a promising pharmacological target for modulating the glial scar after brain ischemia and facilitating tissue regeneration.https://elifesciences.org/articles/96076cell regenerationastrocytesMCAOextracellular matrixglial scar |
| spellingShingle | Maria Ardaya Marie-Catherine Tiveron Harold Cremer Esther Rubio-López Abraham Martín Benjamin Dehay Fernando Pérez-Cerdá Carlos Matute Federico N Soria Fabio Cavaliere Gliogenesis from the subventricular zone modulates the extracellular matrix at the glial scar after brain ischemia eLife cell regeneration astrocytes MCAO extracellular matrix glial scar |
| title | Gliogenesis from the subventricular zone modulates the extracellular matrix at the glial scar after brain ischemia |
| title_full | Gliogenesis from the subventricular zone modulates the extracellular matrix at the glial scar after brain ischemia |
| title_fullStr | Gliogenesis from the subventricular zone modulates the extracellular matrix at the glial scar after brain ischemia |
| title_full_unstemmed | Gliogenesis from the subventricular zone modulates the extracellular matrix at the glial scar after brain ischemia |
| title_short | Gliogenesis from the subventricular zone modulates the extracellular matrix at the glial scar after brain ischemia |
| title_sort | gliogenesis from the subventricular zone modulates the extracellular matrix at the glial scar after brain ischemia |
| topic | cell regeneration astrocytes MCAO extracellular matrix glial scar |
| url | https://elifesciences.org/articles/96076 |
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