CCL5/CCR5-mediated peripheral inflammation exacerbates blood‒brain barrier disruption after intracerebral hemorrhage in mice
Abstract Background Owing to metabolic disequilibrium and immune suppression, intracerebral hemorrhage (ICH) patients are prone to infections; according to a recent global analysis of stroke cases, approximately 10 million new-onset ICH patients had experienced concurrent infection. However, the int...
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-023-04044-3 |
| _version_ | 1797863706731741184 |
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| author | Jie Lin Ya Xu Peiwen Guo Yù-Jié Chen Jiru Zhou Min Xia Binbin Tan Xin Liu Hua Feng Yujie Chen |
| author_facet | Jie Lin Ya Xu Peiwen Guo Yù-Jié Chen Jiru Zhou Min Xia Binbin Tan Xin Liu Hua Feng Yujie Chen |
| author_sort | Jie Lin |
| collection | DOAJ |
| description | Abstract Background Owing to metabolic disequilibrium and immune suppression, intracerebral hemorrhage (ICH) patients are prone to infections; according to a recent global analysis of stroke cases, approximately 10 million new-onset ICH patients had experienced concurrent infection. However, the intrinsic mechanisms underlying the effects of infection related peripheral inflammation after ICH remain unclear. Methods Lipopolysaccharide (LPS) was intraperitoneally injected into ICH model mice to induce peripheral inflammation. Neurobehavioral deficits, blood‒brain barrier (BBB) disruption, and the expression of CCR5, JAK2, STAT3, and MMP9 were evaluated after treatment with recombinant CCL5 (rCCL5) (a CCR5 ligand), maraviroc (MVC) (an FDA-approved selective CCR5 antagonist), or JAK2 CRISPR plasmids. Results Our study revealed that severe peripheral inflammation increased CCL5/CCR5 axis activation in multiple inflammatory cell types, including microglia, astrocytes, and monocytes, and aggravated BBB disruption and neurobehavioral dysfunction after ICH, possibly in part through the JAK2/STAT3 signaling pathway. Conclusions CCR5 might be a potential target for the clinical treatment of infection-induced exacerbation of BBB disruption following ICH. |
| first_indexed | 2024-04-09T22:41:01Z |
| format | Article |
| id | doaj.art-ee158ac5b6fb4200abef691fc6dd9b18 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-09T22:41:01Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-ee158ac5b6fb4200abef691fc6dd9b182023-03-22T12:13:49ZengBMCJournal of Translational Medicine1479-58762023-03-0121111910.1186/s12967-023-04044-3CCL5/CCR5-mediated peripheral inflammation exacerbates blood‒brain barrier disruption after intracerebral hemorrhage in miceJie Lin0Ya Xu1Peiwen Guo2Yù-Jié Chen3Jiru Zhou4Min Xia5Binbin Tan6Xin Liu7Hua Feng8Yujie Chen9Department of Neurosurgery and State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University)Department of Neurosurgery and State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University)Department of Neurosurgery and State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University)Department of Neurosurgery and State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University)Department of Neurosurgery and State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University)Department of Neurosurgery and State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University)Department of Neurosurgery and State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University)Clinical Medical Research Center, Southwest Hospital, Third Military Medical University (Army Medical University)Department of Neurosurgery and State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University)Department of Neurosurgery and State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University)Abstract Background Owing to metabolic disequilibrium and immune suppression, intracerebral hemorrhage (ICH) patients are prone to infections; according to a recent global analysis of stroke cases, approximately 10 million new-onset ICH patients had experienced concurrent infection. However, the intrinsic mechanisms underlying the effects of infection related peripheral inflammation after ICH remain unclear. Methods Lipopolysaccharide (LPS) was intraperitoneally injected into ICH model mice to induce peripheral inflammation. Neurobehavioral deficits, blood‒brain barrier (BBB) disruption, and the expression of CCR5, JAK2, STAT3, and MMP9 were evaluated after treatment with recombinant CCL5 (rCCL5) (a CCR5 ligand), maraviroc (MVC) (an FDA-approved selective CCR5 antagonist), or JAK2 CRISPR plasmids. Results Our study revealed that severe peripheral inflammation increased CCL5/CCR5 axis activation in multiple inflammatory cell types, including microglia, astrocytes, and monocytes, and aggravated BBB disruption and neurobehavioral dysfunction after ICH, possibly in part through the JAK2/STAT3 signaling pathway. Conclusions CCR5 might be a potential target for the clinical treatment of infection-induced exacerbation of BBB disruption following ICH.https://doi.org/10.1186/s12967-023-04044-3Intracerebral hemorrhageBlood‒brain barrierC–C chemokine receptor 5Peripheral inflammationNeuroinflammationBrain-periphery crosstalk |
| spellingShingle | Jie Lin Ya Xu Peiwen Guo Yù-Jié Chen Jiru Zhou Min Xia Binbin Tan Xin Liu Hua Feng Yujie Chen CCL5/CCR5-mediated peripheral inflammation exacerbates blood‒brain barrier disruption after intracerebral hemorrhage in mice Journal of Translational Medicine Intracerebral hemorrhage Blood‒brain barrier C–C chemokine receptor 5 Peripheral inflammation Neuroinflammation Brain-periphery crosstalk |
| title | CCL5/CCR5-mediated peripheral inflammation exacerbates blood‒brain barrier disruption after intracerebral hemorrhage in mice |
| title_full | CCL5/CCR5-mediated peripheral inflammation exacerbates blood‒brain barrier disruption after intracerebral hemorrhage in mice |
| title_fullStr | CCL5/CCR5-mediated peripheral inflammation exacerbates blood‒brain barrier disruption after intracerebral hemorrhage in mice |
| title_full_unstemmed | CCL5/CCR5-mediated peripheral inflammation exacerbates blood‒brain barrier disruption after intracerebral hemorrhage in mice |
| title_short | CCL5/CCR5-mediated peripheral inflammation exacerbates blood‒brain barrier disruption after intracerebral hemorrhage in mice |
| title_sort | ccl5 ccr5 mediated peripheral inflammation exacerbates blood brain barrier disruption after intracerebral hemorrhage in mice |
| topic | Intracerebral hemorrhage Blood‒brain barrier C–C chemokine receptor 5 Peripheral inflammation Neuroinflammation Brain-periphery crosstalk |
| url | https://doi.org/10.1186/s12967-023-04044-3 |
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