C1-inhibitor to prevent intracerebral hemorrhage-related secondary brain injury
Abstract Background Preclinical studies indicate that the systemic application of C1-inhibitor, clinically used to treat hereditary angioedema, reduces secondary brain injury after ischemic stroke. This study assessed the effect of C1-inhibitor on secondary brain injury after hemorrhagic stroke. Met...
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BMC
2024-11-01
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| Series: | Fluids and Barriers of the CNS |
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| Online Access: | https://doi.org/10.1186/s12987-024-00594-w |
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| author | Kevin Akeret Bart R. Thomson Subhajit Ghosh Marc Nolte Urs Fischer Rok Humar Luca Regli Dominik J. Schaer Michael Hugelshofer Raphael M. Buzzi |
| author_facet | Kevin Akeret Bart R. Thomson Subhajit Ghosh Marc Nolte Urs Fischer Rok Humar Luca Regli Dominik J. Schaer Michael Hugelshofer Raphael M. Buzzi |
| author_sort | Kevin Akeret |
| collection | DOAJ |
| description | Abstract Background Preclinical studies indicate that the systemic application of C1-inhibitor, clinically used to treat hereditary angioedema, reduces secondary brain injury after ischemic stroke. This study assessed the effect of C1-inhibitor on secondary brain injury after hemorrhagic stroke. Methods We used an established striatal whole-blood injection mouse model to mimic intracerebral hemorrhage-related secondary brain injury. Based on the spatiotemporal dynamics in our model, we calculated the necessary sample size (n = 24) and determined the most sensitive time point to detect potential group differences (48 h) prior to the experiments. The experimental setup, tissue processing and image analysis adhered to our published protocol. We randomized mice into three groups: C1-inhibitor treatment, placebo, and sham. Histology was standardized by taking eight anatomically predefined slices across the entire lesion. Lesion size, vascular leakage, and inflammatory responses were assessed using automated thresholding and dextran/ICAM1/CD45 intensity mapping. Investigators were blinded to group allocation during the experiment, tissue processing, and image analysis. Results Whole blood injection resulted in significantly larger lesion size and more pronounced vascular leakage and cellular inflammation compared to the sham group. However, there was no difference in lesion size or inflammatory markers between the C1-inhibitor and placebo groups. In addition, there was no difference in the inflammatory response of the choroid plexus, which has been identified as a central organ orchestrating inflammation after intracerebral hemorrhage. Conclusion The protective effect of C1-inhibitor might be isolated to pathophysiological processes with a predominant thromboinflammatory component, as in ischemia-reperfusion, but less so in permanent ischemia or intracerebral hemorrhage. |
| format | Article |
| id | doaj-art-b90e2be5cd7a47cfbeb235f71f463085 |
| institution | Kabale University |
| issn | 2045-8118 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Fluids and Barriers of the CNS |
| spelling | doaj-art-b90e2be5cd7a47cfbeb235f71f4630852024-11-17T12:43:03ZengBMCFluids and Barriers of the CNS2045-81182024-11-012111510.1186/s12987-024-00594-wC1-inhibitor to prevent intracerebral hemorrhage-related secondary brain injuryKevin Akeret0Bart R. Thomson1Subhajit Ghosh2Marc Nolte3Urs Fischer4Rok Humar5Luca Regli6Dominik J. Schaer7Michael Hugelshofer8Raphael M. Buzzi9Department of Neurosurgery, Clinical Neuroscience Center, Universitätsspital und Universität ZürichDepartment of Neurosurgery, Clinical Neuroscience Center, Universitätsspital und Universität ZürichCSL Innovation GmbHCSL Innovation GmbHDepartment of Neurology, Universität BernDivision of Internal Medicine, Universitätsspital und Universität ZürichDepartment of Neurosurgery, Clinical Neuroscience Center, Universitätsspital und Universität ZürichDivision of Internal Medicine, Universitätsspital und Universität ZürichDepartment of Neurosurgery, Clinical Neuroscience Center, Universitätsspital und Universität ZürichDivision of Internal Medicine, Universitätsspital und Universität ZürichAbstract Background Preclinical studies indicate that the systemic application of C1-inhibitor, clinically used to treat hereditary angioedema, reduces secondary brain injury after ischemic stroke. This study assessed the effect of C1-inhibitor on secondary brain injury after hemorrhagic stroke. Methods We used an established striatal whole-blood injection mouse model to mimic intracerebral hemorrhage-related secondary brain injury. Based on the spatiotemporal dynamics in our model, we calculated the necessary sample size (n = 24) and determined the most sensitive time point to detect potential group differences (48 h) prior to the experiments. The experimental setup, tissue processing and image analysis adhered to our published protocol. We randomized mice into three groups: C1-inhibitor treatment, placebo, and sham. Histology was standardized by taking eight anatomically predefined slices across the entire lesion. Lesion size, vascular leakage, and inflammatory responses were assessed using automated thresholding and dextran/ICAM1/CD45 intensity mapping. Investigators were blinded to group allocation during the experiment, tissue processing, and image analysis. Results Whole blood injection resulted in significantly larger lesion size and more pronounced vascular leakage and cellular inflammation compared to the sham group. However, there was no difference in lesion size or inflammatory markers between the C1-inhibitor and placebo groups. In addition, there was no difference in the inflammatory response of the choroid plexus, which has been identified as a central organ orchestrating inflammation after intracerebral hemorrhage. Conclusion The protective effect of C1-inhibitor might be isolated to pathophysiological processes with a predominant thromboinflammatory component, as in ischemia-reperfusion, but less so in permanent ischemia or intracerebral hemorrhage.https://doi.org/10.1186/s12987-024-00594-wChoroid plexusNeuroinflammationStrokeQuantitative histology. |
| spellingShingle | Kevin Akeret Bart R. Thomson Subhajit Ghosh Marc Nolte Urs Fischer Rok Humar Luca Regli Dominik J. Schaer Michael Hugelshofer Raphael M. Buzzi C1-inhibitor to prevent intracerebral hemorrhage-related secondary brain injury Fluids and Barriers of the CNS Choroid plexus Neuroinflammation Stroke Quantitative histology. |
| title | C1-inhibitor to prevent intracerebral hemorrhage-related secondary brain injury |
| title_full | C1-inhibitor to prevent intracerebral hemorrhage-related secondary brain injury |
| title_fullStr | C1-inhibitor to prevent intracerebral hemorrhage-related secondary brain injury |
| title_full_unstemmed | C1-inhibitor to prevent intracerebral hemorrhage-related secondary brain injury |
| title_short | C1-inhibitor to prevent intracerebral hemorrhage-related secondary brain injury |
| title_sort | c1 inhibitor to prevent intracerebral hemorrhage related secondary brain injury |
| topic | Choroid plexus Neuroinflammation Stroke Quantitative histology. |
| url | https://doi.org/10.1186/s12987-024-00594-w |
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