A Preliminary Study of Effect of Melatonin on Inflammation and Hypoxia‐Related Factors in a Mouse Model of Elastase‐Induced Intracranial Aneurysm
ABSTRACT Introduction Intracranial aneurysms (IAs) are relatively common cerebrovascular anomalies. Melatonin could modulate inflammatory and offers neuroprotective effects, and its role in IA has not been fully elucidated. Methods An elastase‐induced IA mouse model was constructed and melatonin (15...
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Wiley
2025-03-01
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| Series: | Brain and Behavior |
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| Online Access: | https://doi.org/10.1002/brb3.70371 |
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| author | NarenYa Yan Feng Yongxing Su Le Chen Yan Liu Zhongwu Sun Zhengfei Ma |
| author_facet | NarenYa Yan Feng Yongxing Su Le Chen Yan Liu Zhongwu Sun Zhengfei Ma |
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| description | ABSTRACT Introduction Intracranial aneurysms (IAs) are relatively common cerebrovascular anomalies. Melatonin could modulate inflammatory and offers neuroprotective effects, and its role in IA has not been fully elucidated. Methods An elastase‐induced IA mouse model was constructed and melatonin (150 mg/kg) was administered to investigate its therapeutic effects on IA. Aneurysm formation was observed by bromophenol blue gelatin perfusion, and the pathology changes in IA mice were examined using hematoxylin‐eosin (HE) staining. The potential mechanisms of melatonin treatment of IA were explored using western blot, enzyme‐linked immunosorbent, real‐time qPCR, immunohistochemistry, and flow cytometry. An H2O2‐reduced human brain vascular smooth muscle cells (HBVSMC) injury model was also constructed. Results The formation of aneurysms was observed in the circle of Willis in the IA mice. Melatonin treatment alleviated the thinning of blood vessel walls and disruption of the internal elastic lamina in IA mice. The levels of Bcl‐2 were significantly increased and Bax and cleaved caspase‐3 were decreased in IA mice with melatonin treatment, suggesting reduced apoptosis. Furthermore, melatonin reduced levels of interleukin (IL)‐1β, IL‐6, and tumor necrosis factor‐alpha (TNF‐α) in IA mice. The H2O2‐reduced HBVSMCs model showed consistent results. Melatonin reduced levels of krüppel‐like factor 6 (KLF6) in IA mice. Importantly, melatonin significantly reduced levels of regulatory T cells (Treg), hypoxia‐inducible factor (HIF)‐1α, nuclear factor interleukin 3‐regulated (NFIL3), TCDD‐inducible poly‐ADP‐ribose polymerase (TIPARP), and increased levels of monocytes in IA mice. Conclusion Melatonin mitigates IA injury by modulating immune cells and hypoxia‐related factors. These findings provide an exploratory foundation for therapeutic strategies in IA. |
| format | Article |
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| language | English |
| publishDate | 2025-03-01 |
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| series | Brain and Behavior |
| spelling | doaj-art-2de748430b69409598c339bba5bf2e352025-08-20T03:08:36ZengWileyBrain and Behavior2162-32792025-03-01153n/an/a10.1002/brb3.70371A Preliminary Study of Effect of Melatonin on Inflammation and Hypoxia‐Related Factors in a Mouse Model of Elastase‐Induced Intracranial AneurysmNarenYa0Yan Feng1Yongxing Su2Le Chen3Yan Liu4Zhongwu Sun5Zhengfei Ma6Department of Neurology The First Affiliated Hospital of Anhui Medical University Hefei Anhui Province People's Republic of ChinaDepartment of Neurology Suzhou Hospital of Anhui Medical University Suzhou Anhui Province People's Republic of ChinaDepartment of Neurology Suzhou Hospital of Anhui Medical University Suzhou Anhui Province People's Republic of ChinaDepartment of Neurology Suzhou Hospital of Anhui Medical University Suzhou Anhui Province People's Republic of ChinaDepartment of Neurology Suzhou Hospital of Anhui Medical University Suzhou Anhui Province People's Republic of ChinaDepartment of Neurology The First Affiliated Hospital of Anhui Medical University Hefei Anhui Province People's Republic of ChinaDepartment of Neurology Suzhou Hospital of Anhui Medical University Suzhou Anhui Province People's Republic of ChinaABSTRACT Introduction Intracranial aneurysms (IAs) are relatively common cerebrovascular anomalies. Melatonin could modulate inflammatory and offers neuroprotective effects, and its role in IA has not been fully elucidated. Methods An elastase‐induced IA mouse model was constructed and melatonin (150 mg/kg) was administered to investigate its therapeutic effects on IA. Aneurysm formation was observed by bromophenol blue gelatin perfusion, and the pathology changes in IA mice were examined using hematoxylin‐eosin (HE) staining. The potential mechanisms of melatonin treatment of IA were explored using western blot, enzyme‐linked immunosorbent, real‐time qPCR, immunohistochemistry, and flow cytometry. An H2O2‐reduced human brain vascular smooth muscle cells (HBVSMC) injury model was also constructed. Results The formation of aneurysms was observed in the circle of Willis in the IA mice. Melatonin treatment alleviated the thinning of blood vessel walls and disruption of the internal elastic lamina in IA mice. The levels of Bcl‐2 were significantly increased and Bax and cleaved caspase‐3 were decreased in IA mice with melatonin treatment, suggesting reduced apoptosis. Furthermore, melatonin reduced levels of interleukin (IL)‐1β, IL‐6, and tumor necrosis factor‐alpha (TNF‐α) in IA mice. The H2O2‐reduced HBVSMCs model showed consistent results. Melatonin reduced levels of krüppel‐like factor 6 (KLF6) in IA mice. Importantly, melatonin significantly reduced levels of regulatory T cells (Treg), hypoxia‐inducible factor (HIF)‐1α, nuclear factor interleukin 3‐regulated (NFIL3), TCDD‐inducible poly‐ADP‐ribose polymerase (TIPARP), and increased levels of monocytes in IA mice. Conclusion Melatonin mitigates IA injury by modulating immune cells and hypoxia‐related factors. These findings provide an exploratory foundation for therapeutic strategies in IA.https://doi.org/10.1002/brb3.70371hypoxiaimmune cellsintracranial aneurysmmelatonin |
| spellingShingle | NarenYa Yan Feng Yongxing Su Le Chen Yan Liu Zhongwu Sun Zhengfei Ma A Preliminary Study of Effect of Melatonin on Inflammation and Hypoxia‐Related Factors in a Mouse Model of Elastase‐Induced Intracranial Aneurysm Brain and Behavior hypoxia immune cells intracranial aneurysm melatonin |
| title | A Preliminary Study of Effect of Melatonin on Inflammation and Hypoxia‐Related Factors in a Mouse Model of Elastase‐Induced Intracranial Aneurysm |
| title_full | A Preliminary Study of Effect of Melatonin on Inflammation and Hypoxia‐Related Factors in a Mouse Model of Elastase‐Induced Intracranial Aneurysm |
| title_fullStr | A Preliminary Study of Effect of Melatonin on Inflammation and Hypoxia‐Related Factors in a Mouse Model of Elastase‐Induced Intracranial Aneurysm |
| title_full_unstemmed | A Preliminary Study of Effect of Melatonin on Inflammation and Hypoxia‐Related Factors in a Mouse Model of Elastase‐Induced Intracranial Aneurysm |
| title_short | A Preliminary Study of Effect of Melatonin on Inflammation and Hypoxia‐Related Factors in a Mouse Model of Elastase‐Induced Intracranial Aneurysm |
| title_sort | preliminary study of effect of melatonin on inflammation and hypoxia related factors in a mouse model of elastase induced intracranial aneurysm |
| topic | hypoxia immune cells intracranial aneurysm melatonin |
| url | https://doi.org/10.1002/brb3.70371 |
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