HIF-1α participates in secondary brain injury through regulating neuroinflammation
A deeper understanding of the underlying biological mechanisms of secondary brain injury induced by traumatic brain injury (TBI) will greatly advance the development of effective treatments for patients with TBI. Hypoxia-inducible factor-1 alpha (HIF-1α) is a central regulator of cellular response t...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
De Gruyter
2023-02-01
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| Series: | Translational Neuroscience |
| Subjects: | |
| Online Access: | https://doi.org/10.1515/tnsci-2022-0272 |
| _version_ | 1797848614403309568 |
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| author | Xu Xiaojian Yang Mengshi Zhang Bin Dong Jinqian Zhuang Yuan Ge Qianqian Niu Fei Liu Baiyun |
| author_facet | Xu Xiaojian Yang Mengshi Zhang Bin Dong Jinqian Zhuang Yuan Ge Qianqian Niu Fei Liu Baiyun |
| author_sort | Xu Xiaojian |
| collection | DOAJ |
| description | A deeper understanding of the underlying biological mechanisms of secondary brain injury induced by traumatic brain injury (TBI) will greatly advance the development of effective treatments for patients with TBI. Hypoxia-inducible factor-1 alpha (HIF-1α) is a central regulator of cellular response to hypoxia. In addition, growing evidence shows that HIF-1α plays the important role in TBI-induced changes in biological processes; however, detailed functional mechanisms are not completely known. The aim of the present work was to further explore HIF-1α-mediated events after TBI. To this end, next-generation sequencing, coupled with cellular and molecular analysis, was adopted to interrogate vulnerable events in a rat controlled cortical impact model of TBI. The results demonstrated that TBI induced accumulation of HIF-1α at the peri-injury site at 24 h post-injury, which was associated with neuronal loss. Moreover, gene set enrichment analysis unveiled that neuroinflammation, especially an innate inflammatory response, was significantly evoked by TBI, which could be attenuated by the inhibition of HIF-1α. Furthermore, the inhibition of HIF-1α could mitigate the activation of microglia and astrocytes. Taken together, all these data implied that HIF-1α might contribute to secondary brain injury through regulating neuroinflammation. |
| first_indexed | 2024-04-09T18:31:27Z |
| format | Article |
| id | doaj.art-ef65478de91d49bca2956f5b477ce232 |
| institution | Directory Open Access Journal |
| issn | 2081-6936 |
| language | English |
| last_indexed | 2024-04-09T18:31:27Z |
| publishDate | 2023-02-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Translational Neuroscience |
| spelling | doaj.art-ef65478de91d49bca2956f5b477ce2322023-04-11T17:07:20ZengDe GruyterTranslational Neuroscience2081-69362023-02-011412869510.1515/tnsci-2022-0272HIF-1α participates in secondary brain injury through regulating neuroinflammationXu Xiaojian0Yang Mengshi1Zhang Bin2Dong Jinqian3Zhuang Yuan4Ge Qianqian5Niu Fei6Liu Baiyun7Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaBeijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaBeijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaBeijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaBeijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaBeijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaBeijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaBeijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaA deeper understanding of the underlying biological mechanisms of secondary brain injury induced by traumatic brain injury (TBI) will greatly advance the development of effective treatments for patients with TBI. Hypoxia-inducible factor-1 alpha (HIF-1α) is a central regulator of cellular response to hypoxia. In addition, growing evidence shows that HIF-1α plays the important role in TBI-induced changes in biological processes; however, detailed functional mechanisms are not completely known. The aim of the present work was to further explore HIF-1α-mediated events after TBI. To this end, next-generation sequencing, coupled with cellular and molecular analysis, was adopted to interrogate vulnerable events in a rat controlled cortical impact model of TBI. The results demonstrated that TBI induced accumulation of HIF-1α at the peri-injury site at 24 h post-injury, which was associated with neuronal loss. Moreover, gene set enrichment analysis unveiled that neuroinflammation, especially an innate inflammatory response, was significantly evoked by TBI, which could be attenuated by the inhibition of HIF-1α. Furthermore, the inhibition of HIF-1α could mitigate the activation of microglia and astrocytes. Taken together, all these data implied that HIF-1α might contribute to secondary brain injury through regulating neuroinflammation.https://doi.org/10.1515/tnsci-2022-0272traumatic brain injuryhif-1αhypoxianeuroinflammationapoptosisinnate immune2-methoxyestradiolsecondary brain injurygseacontrolled cortical impact |
| spellingShingle | Xu Xiaojian Yang Mengshi Zhang Bin Dong Jinqian Zhuang Yuan Ge Qianqian Niu Fei Liu Baiyun HIF-1α participates in secondary brain injury through regulating neuroinflammation Translational Neuroscience traumatic brain injury hif-1α hypoxia neuroinflammation apoptosis innate immune 2-methoxyestradiol secondary brain injury gsea controlled cortical impact |
| title | HIF-1α participates in secondary brain injury through regulating neuroinflammation |
| title_full | HIF-1α participates in secondary brain injury through regulating neuroinflammation |
| title_fullStr | HIF-1α participates in secondary brain injury through regulating neuroinflammation |
| title_full_unstemmed | HIF-1α participates in secondary brain injury through regulating neuroinflammation |
| title_short | HIF-1α participates in secondary brain injury through regulating neuroinflammation |
| title_sort | hif 1α participates in secondary brain injury through regulating neuroinflammation |
| topic | traumatic brain injury hif-1α hypoxia neuroinflammation apoptosis innate immune 2-methoxyestradiol secondary brain injury gsea controlled cortical impact |
| url | https://doi.org/10.1515/tnsci-2022-0272 |
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