Microglial replacement in the aged brain restricts neuroinflammation following intracerebral hemorrhage
Abstract Aged microglia display augmented inflammatory activity after neural injury. Although aging is a risk factor for poor outcome after brain insults, the precise impact of aging-related alterations in microglia on neural injury remains poorly understood. Microglia can be eliminated via pharmaco...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-01-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-021-04424-x |
| _version_ | 1798026220195020800 |
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| author | Xiuping Li Xiaolin Gao Wenyan Zhang Mingming Liu Zhaoli Han Minshu Li Ping Lei Qiang Liu |
| author_facet | Xiuping Li Xiaolin Gao Wenyan Zhang Mingming Liu Zhaoli Han Minshu Li Ping Lei Qiang Liu |
| author_sort | Xiuping Li |
| collection | DOAJ |
| description | Abstract Aged microglia display augmented inflammatory activity after neural injury. Although aging is a risk factor for poor outcome after brain insults, the precise impact of aging-related alterations in microglia on neural injury remains poorly understood. Microglia can be eliminated via pharmacological inhibition of the colony–stimulating factor 1 receptor (CSF1R). Upon withdrawal of CSF1R inhibitors, microglia rapidly repopulate the entire brain, leading to replacement of the microglial compartment. In this study, we investigated the impact of microglial replacement in the aged brain on neural injury using a mouse model of intracerebral hemorrhage (ICH) induced by collagenase injection. We found that replacement of microglia in the aged brain reduced neurological deficits and brain edema after ICH. Microglial replacement-induced attenuation of ICH injury was accompanied with alleviated blood-brain barrier disruption and leukocyte infiltration. Notably, newly repopulated microglia had reduced expression of IL-1β, TNF-α and CD86, and upregulation of CD206 in response to ICH. Our findings suggest that replacement of microglia in the aged brain restricts neuroinflammation and brain injury following ICH. |
| first_indexed | 2024-04-11T18:31:47Z |
| format | Article |
| id | doaj.art-3c6dc5c6843749718ed508c4c1cf0267 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-11T18:31:47Z |
| publishDate | 2022-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-3c6dc5c6843749718ed508c4c1cf02672022-12-22T04:09:25ZengNature Publishing GroupCell Death and Disease2041-48892022-01-011311710.1038/s41419-021-04424-xMicroglial replacement in the aged brain restricts neuroinflammation following intracerebral hemorrhageXiuping Li0Xiaolin Gao1Wenyan Zhang2Mingming Liu3Zhaoli Han4Minshu Li5Ping Lei6Qiang Liu7Department of Neurology, Aging and Neurodegenerative Disease Laboratory, Tianjin Neurological Institute, Tianjin Medical University General HospitalDepartment of Neurology, Aging and Neurodegenerative Disease Laboratory, Tianjin Neurological Institute, Tianjin Medical University General HospitalDepartment of Neurology, Aging and Neurodegenerative Disease Laboratory, Tianjin Neurological Institute, Tianjin Medical University General HospitalDepartment of Neurology, Aging and Neurodegenerative Disease Laboratory, Tianjin Neurological Institute, Tianjin Medical University General HospitalDepartment of Geriatrics, Tianjin Geriatrics Institute, Tianjin Medical University General HospitalDepartment of Neurology, Aging and Neurodegenerative Disease Laboratory, Tianjin Neurological Institute, Tianjin Medical University General HospitalDepartment of Geriatrics, Tianjin Geriatrics Institute, Tianjin Medical University General HospitalDepartment of Neurology, Aging and Neurodegenerative Disease Laboratory, Tianjin Neurological Institute, Tianjin Medical University General HospitalAbstract Aged microglia display augmented inflammatory activity after neural injury. Although aging is a risk factor for poor outcome after brain insults, the precise impact of aging-related alterations in microglia on neural injury remains poorly understood. Microglia can be eliminated via pharmacological inhibition of the colony–stimulating factor 1 receptor (CSF1R). Upon withdrawal of CSF1R inhibitors, microglia rapidly repopulate the entire brain, leading to replacement of the microglial compartment. In this study, we investigated the impact of microglial replacement in the aged brain on neural injury using a mouse model of intracerebral hemorrhage (ICH) induced by collagenase injection. We found that replacement of microglia in the aged brain reduced neurological deficits and brain edema after ICH. Microglial replacement-induced attenuation of ICH injury was accompanied with alleviated blood-brain barrier disruption and leukocyte infiltration. Notably, newly repopulated microglia had reduced expression of IL-1β, TNF-α and CD86, and upregulation of CD206 in response to ICH. Our findings suggest that replacement of microglia in the aged brain restricts neuroinflammation and brain injury following ICH.https://doi.org/10.1038/s41419-021-04424-x |
| spellingShingle | Xiuping Li Xiaolin Gao Wenyan Zhang Mingming Liu Zhaoli Han Minshu Li Ping Lei Qiang Liu Microglial replacement in the aged brain restricts neuroinflammation following intracerebral hemorrhage Cell Death and Disease |
| title | Microglial replacement in the aged brain restricts neuroinflammation following intracerebral hemorrhage |
| title_full | Microglial replacement in the aged brain restricts neuroinflammation following intracerebral hemorrhage |
| title_fullStr | Microglial replacement in the aged brain restricts neuroinflammation following intracerebral hemorrhage |
| title_full_unstemmed | Microglial replacement in the aged brain restricts neuroinflammation following intracerebral hemorrhage |
| title_short | Microglial replacement in the aged brain restricts neuroinflammation following intracerebral hemorrhage |
| title_sort | microglial replacement in the aged brain restricts neuroinflammation following intracerebral hemorrhage |
| url | https://doi.org/10.1038/s41419-021-04424-x |
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