Interleukin-18 interacts with NKCC1 to mediate brain injury after intracerebral hemorrhage
Interleukin 18 (IL-18), a proinflammatory cytokine, has been implicated in various neurological disorders, including cerebrovascular disease and psychiatric disorders. In a previous study, IL-18 was observed to activate microglia and enhance the inflammatory response following intracranial hemorrhag...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-12-01
|
| Series: | Brain, Behavior, & Immunity - Health |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666354624001686 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850058137972768768 |
|---|---|
| author | Beibei Xu Hao Li He Zheng Zhongyu Gao Zhigang Miao Xingshun Xu Hao Yang Yi Yang |
| author_facet | Beibei Xu Hao Li He Zheng Zhongyu Gao Zhigang Miao Xingshun Xu Hao Yang Yi Yang |
| author_sort | Beibei Xu |
| collection | DOAJ |
| description | Interleukin 18 (IL-18), a proinflammatory cytokine, has been implicated in various neurological disorders, including cerebrovascular disease and psychiatric disorders. In a previous study, IL-18 was observed to activate microglia and enhance the inflammatory response following intracranial hemorrhage (ICH). However, the underlying mechanism remains unclear. In the present study, we found that IL-18 and IL-18 receptor (IL-18 R) are primarily secreted by neurons during the early stages after ICH, with microglia becoming the predominant source at 12–24 h after ICH. Meanwhile, the expression level of IL-18 R increased following ICH, along with an augmentation in the binding affinity of IL-18 R to IL-18. Subsequently, the deficiency of IL-18 R mitigated neurological impairment and subsequent activation of inflammatory pathways in mice post-ICH. Moreover, our findings suggest that IL-18-induced neurological injury after ICH may be mediated by the interaction between IL18R and NKCC1. Significantly, the NKCC1 inhibitor rescued the neurologic injury after ICH. In conclusion, our study suggests that targeting the IL-18/IL-18R/NKCC1 pathway could be an effective therapeutic strategy to attenuate secondary brain injury after ICH. |
| format | Article |
| id | doaj-art-fb00d284fd4b49019758d599740d1e6f |
| institution | DOAJ |
| issn | 2666-3546 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain, Behavior, & Immunity - Health |
| spelling | doaj-art-fb00d284fd4b49019758d599740d1e6f2025-08-20T02:51:14ZengElsevierBrain, Behavior, & Immunity - Health2666-35462024-12-014210089010.1016/j.bbih.2024.100890Interleukin-18 interacts with NKCC1 to mediate brain injury after intracerebral hemorrhageBeibei Xu0Hao Li1He Zheng2Zhongyu Gao3Zhigang Miao4Xingshun Xu5Hao Yang6Yi Yang7Departments of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, ChinaDepartments of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China; Departments of Neurology, The Fourth Affiliated Hospital of Soochow University, Suzhou, Jiangsu, ChinaDepartments of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, ChinaComputer Science and Engineering, University of California Davis, One Shields Avenue, Davis, CA, 95616, USAInstitute of Neuroscience, Soochow University, Suzhou, Jiangsu, ChinaDepartments of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China; Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, China; Corresponding author. Departments of Neurology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.Department of Fetology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China; Corresponding author.Departments of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China; Corresponding author.Interleukin 18 (IL-18), a proinflammatory cytokine, has been implicated in various neurological disorders, including cerebrovascular disease and psychiatric disorders. In a previous study, IL-18 was observed to activate microglia and enhance the inflammatory response following intracranial hemorrhage (ICH). However, the underlying mechanism remains unclear. In the present study, we found that IL-18 and IL-18 receptor (IL-18 R) are primarily secreted by neurons during the early stages after ICH, with microglia becoming the predominant source at 12–24 h after ICH. Meanwhile, the expression level of IL-18 R increased following ICH, along with an augmentation in the binding affinity of IL-18 R to IL-18. Subsequently, the deficiency of IL-18 R mitigated neurological impairment and subsequent activation of inflammatory pathways in mice post-ICH. Moreover, our findings suggest that IL-18-induced neurological injury after ICH may be mediated by the interaction between IL18R and NKCC1. Significantly, the NKCC1 inhibitor rescued the neurologic injury after ICH. In conclusion, our study suggests that targeting the IL-18/IL-18R/NKCC1 pathway could be an effective therapeutic strategy to attenuate secondary brain injury after ICH.http://www.sciencedirect.com/science/article/pii/S2666354624001686Interleukin-18Intracerebral hemorrhageBrain injuryMicrogliaNKCC1 |
| spellingShingle | Beibei Xu Hao Li He Zheng Zhongyu Gao Zhigang Miao Xingshun Xu Hao Yang Yi Yang Interleukin-18 interacts with NKCC1 to mediate brain injury after intracerebral hemorrhage Brain, Behavior, & Immunity - Health Interleukin-18 Intracerebral hemorrhage Brain injury Microglia NKCC1 |
| title | Interleukin-18 interacts with NKCC1 to mediate brain injury after intracerebral hemorrhage |
| title_full | Interleukin-18 interacts with NKCC1 to mediate brain injury after intracerebral hemorrhage |
| title_fullStr | Interleukin-18 interacts with NKCC1 to mediate brain injury after intracerebral hemorrhage |
| title_full_unstemmed | Interleukin-18 interacts with NKCC1 to mediate brain injury after intracerebral hemorrhage |
| title_short | Interleukin-18 interacts with NKCC1 to mediate brain injury after intracerebral hemorrhage |
| title_sort | interleukin 18 interacts with nkcc1 to mediate brain injury after intracerebral hemorrhage |
| topic | Interleukin-18 Intracerebral hemorrhage Brain injury Microglia NKCC1 |
| url | http://www.sciencedirect.com/science/article/pii/S2666354624001686 |
| work_keys_str_mv | AT beibeixu interleukin18interactswithnkcc1tomediatebraininjuryafterintracerebralhemorrhage AT haoli interleukin18interactswithnkcc1tomediatebraininjuryafterintracerebralhemorrhage AT hezheng interleukin18interactswithnkcc1tomediatebraininjuryafterintracerebralhemorrhage AT zhongyugao interleukin18interactswithnkcc1tomediatebraininjuryafterintracerebralhemorrhage AT zhigangmiao interleukin18interactswithnkcc1tomediatebraininjuryafterintracerebralhemorrhage AT xingshunxu interleukin18interactswithnkcc1tomediatebraininjuryafterintracerebralhemorrhage AT haoyang interleukin18interactswithnkcc1tomediatebraininjuryafterintracerebralhemorrhage AT yiyang interleukin18interactswithnkcc1tomediatebraininjuryafterintracerebralhemorrhage |