Blood Progenitor Cell Mobilization Driven by TWEAK Promotes Neovascularization and Reduces Brain Damage in a Rat Model of Intracerebral Hemorrhage
Non-traumatic intracerebral hemorrhage (ICH) is one of the most devastating and disabling forms of stroke; however, there are no effective pharmacological therapies available following the insult. Angiogenesis appears as a key step to overcoming the damage and promoting functional recovery. In this...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-05-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/14/5/601 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850127456802963456 |
|---|---|
| author | Daniel Romaus-Sanjurjo Esteban López-Arias Cristina Rodríguez Pablo Hervella Mariña Rodríguez-Arrizabalaga Manuel Debasa-Mouce Juan Manuel Pías-Peleteiro Ramón Iglesias-Rey Pablo Aguiar Ángeles Almeida José Castillo Alberto Ouro Tomás Sobrino |
| author_facet | Daniel Romaus-Sanjurjo Esteban López-Arias Cristina Rodríguez Pablo Hervella Mariña Rodríguez-Arrizabalaga Manuel Debasa-Mouce Juan Manuel Pías-Peleteiro Ramón Iglesias-Rey Pablo Aguiar Ángeles Almeida José Castillo Alberto Ouro Tomás Sobrino |
| author_sort | Daniel Romaus-Sanjurjo |
| collection | DOAJ |
| description | Non-traumatic intracerebral hemorrhage (ICH) is one of the most devastating and disabling forms of stroke; however, there are no effective pharmacological therapies available following the insult. Angiogenesis appears as a key step to overcoming the damage and promoting functional recovery. In this context, endothelial progenitor cells (EPCs) mobilization improves oxidative stress and promotes neovascularization, which has been linked to beneficial outcomes following both ischemic and hemorrhagic stroke. The TNF-like weak inducer of apoptosis (TWEAK), binding to its receptor Fn14, has been suggested as an inducer of EPCs differentiation, viability and migration to the injury site in a model of myocardial infarction. Here, we have performed a proof-of-concept preclinical study in a rat model of ICH where we report that a 50 μg/kg dose of rat recombinant TWEAK (rTWEAK) promotes blood progenitor cells mobilization, mainly EPCs. As soon as 72 h post-injury, brain neovascularization, and, importantly, long-term hematoma reduction and improved functional recovery is reported. In contrast, a higher dose of 150 μg/kg blocked those beneficial outcomes. Therefore, a low dose of rTWEAK treatment promotes neovascularization and reduces brain damage in a rat model of ICH. Further clinical studies will be needed to demonstrate if rTWEAK could represent a new strategy to promote recovery following ICH. |
| format | Article |
| id | doaj-art-89875292a9914ee7bfe1d4c43059053e |
| institution | OA Journals |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj-art-89875292a9914ee7bfe1d4c43059053e2025-08-20T02:33:39ZengMDPI AGAntioxidants2076-39212025-05-0114560110.3390/antiox14050601Blood Progenitor Cell Mobilization Driven by TWEAK Promotes Neovascularization and Reduces Brain Damage in a Rat Model of Intracerebral HemorrhageDaniel Romaus-Sanjurjo0Esteban López-Arias1Cristina Rodríguez2Pablo Hervella3Mariña Rodríguez-Arrizabalaga4Manuel Debasa-Mouce5Juan Manuel Pías-Peleteiro6Ramón Iglesias-Rey7Pablo Aguiar8Ángeles Almeida9José Castillo10Alberto Ouro11Tomás Sobrino12NeuroAging Group Laboratory (NEURAL), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, SpainNeuroAging Group Laboratory (NEURAL), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, SpainInstitute of Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca, CSIC, University of Salamanca, 37007 Salamanca, SpainNeuroimaging and Biotechnology Laboratory (NOBEL), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, SpainNeuroAging Group Laboratory (NEURAL), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, SpainNeuroAging Group Laboratory (NEURAL), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, SpainNeuroAging Group Laboratory (NEURAL), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, SpainNeuroimaging and Biotechnology Laboratory (NOBEL), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, SpainCentro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, 28029 Madrid, SpainInstitute of Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca, CSIC, University of Salamanca, 37007 Salamanca, SpainNeuroimaging and Biotechnology Laboratory (NOBEL), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, SpainNeuroAging Group Laboratory (NEURAL), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, SpainNeuroAging Group Laboratory (NEURAL), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, SpainNon-traumatic intracerebral hemorrhage (ICH) is one of the most devastating and disabling forms of stroke; however, there are no effective pharmacological therapies available following the insult. Angiogenesis appears as a key step to overcoming the damage and promoting functional recovery. In this context, endothelial progenitor cells (EPCs) mobilization improves oxidative stress and promotes neovascularization, which has been linked to beneficial outcomes following both ischemic and hemorrhagic stroke. The TNF-like weak inducer of apoptosis (TWEAK), binding to its receptor Fn14, has been suggested as an inducer of EPCs differentiation, viability and migration to the injury site in a model of myocardial infarction. Here, we have performed a proof-of-concept preclinical study in a rat model of ICH where we report that a 50 μg/kg dose of rat recombinant TWEAK (rTWEAK) promotes blood progenitor cells mobilization, mainly EPCs. As soon as 72 h post-injury, brain neovascularization, and, importantly, long-term hematoma reduction and improved functional recovery is reported. In contrast, a higher dose of 150 μg/kg blocked those beneficial outcomes. Therefore, a low dose of rTWEAK treatment promotes neovascularization and reduces brain damage in a rat model of ICH. Further clinical studies will be needed to demonstrate if rTWEAK could represent a new strategy to promote recovery following ICH.https://www.mdpi.com/2076-3921/14/5/601endothelial progenitor cellsintracerebral hemorrhageneovascularizationTWEAK |
| spellingShingle | Daniel Romaus-Sanjurjo Esteban López-Arias Cristina Rodríguez Pablo Hervella Mariña Rodríguez-Arrizabalaga Manuel Debasa-Mouce Juan Manuel Pías-Peleteiro Ramón Iglesias-Rey Pablo Aguiar Ángeles Almeida José Castillo Alberto Ouro Tomás Sobrino Blood Progenitor Cell Mobilization Driven by TWEAK Promotes Neovascularization and Reduces Brain Damage in a Rat Model of Intracerebral Hemorrhage Antioxidants endothelial progenitor cells intracerebral hemorrhage neovascularization TWEAK |
| title | Blood Progenitor Cell Mobilization Driven by TWEAK Promotes Neovascularization and Reduces Brain Damage in a Rat Model of Intracerebral Hemorrhage |
| title_full | Blood Progenitor Cell Mobilization Driven by TWEAK Promotes Neovascularization and Reduces Brain Damage in a Rat Model of Intracerebral Hemorrhage |
| title_fullStr | Blood Progenitor Cell Mobilization Driven by TWEAK Promotes Neovascularization and Reduces Brain Damage in a Rat Model of Intracerebral Hemorrhage |
| title_full_unstemmed | Blood Progenitor Cell Mobilization Driven by TWEAK Promotes Neovascularization and Reduces Brain Damage in a Rat Model of Intracerebral Hemorrhage |
| title_short | Blood Progenitor Cell Mobilization Driven by TWEAK Promotes Neovascularization and Reduces Brain Damage in a Rat Model of Intracerebral Hemorrhage |
| title_sort | blood progenitor cell mobilization driven by tweak promotes neovascularization and reduces brain damage in a rat model of intracerebral hemorrhage |
| topic | endothelial progenitor cells intracerebral hemorrhage neovascularization TWEAK |
| url | https://www.mdpi.com/2076-3921/14/5/601 |
| work_keys_str_mv | AT danielromaussanjurjo bloodprogenitorcellmobilizationdrivenbytweakpromotesneovascularizationandreducesbraindamageinaratmodelofintracerebralhemorrhage AT estebanlopezarias bloodprogenitorcellmobilizationdrivenbytweakpromotesneovascularizationandreducesbraindamageinaratmodelofintracerebralhemorrhage AT cristinarodriguez bloodprogenitorcellmobilizationdrivenbytweakpromotesneovascularizationandreducesbraindamageinaratmodelofintracerebralhemorrhage AT pablohervella bloodprogenitorcellmobilizationdrivenbytweakpromotesneovascularizationandreducesbraindamageinaratmodelofintracerebralhemorrhage AT marinarodriguezarrizabalaga bloodprogenitorcellmobilizationdrivenbytweakpromotesneovascularizationandreducesbraindamageinaratmodelofintracerebralhemorrhage AT manueldebasamouce bloodprogenitorcellmobilizationdrivenbytweakpromotesneovascularizationandreducesbraindamageinaratmodelofintracerebralhemorrhage AT juanmanuelpiaspeleteiro bloodprogenitorcellmobilizationdrivenbytweakpromotesneovascularizationandreducesbraindamageinaratmodelofintracerebralhemorrhage AT ramoniglesiasrey bloodprogenitorcellmobilizationdrivenbytweakpromotesneovascularizationandreducesbraindamageinaratmodelofintracerebralhemorrhage AT pabloaguiar bloodprogenitorcellmobilizationdrivenbytweakpromotesneovascularizationandreducesbraindamageinaratmodelofintracerebralhemorrhage AT angelesalmeida bloodprogenitorcellmobilizationdrivenbytweakpromotesneovascularizationandreducesbraindamageinaratmodelofintracerebralhemorrhage AT josecastillo bloodprogenitorcellmobilizationdrivenbytweakpromotesneovascularizationandreducesbraindamageinaratmodelofintracerebralhemorrhage AT albertoouro bloodprogenitorcellmobilizationdrivenbytweakpromotesneovascularizationandreducesbraindamageinaratmodelofintracerebralhemorrhage AT tomassobrino bloodprogenitorcellmobilizationdrivenbytweakpromotesneovascularizationandreducesbraindamageinaratmodelofintracerebralhemorrhage |