CNS-associated macrophages contribute to intracerebral aneurysm pathophysiology
Abstract Intracerebral aneurysms (IAs) are pathological dilatations of cerebral arteries whose rupture leads to subarachnoid hemorrhage, a significant cause of disability and death. Inflammation is recognized as a critical contributor to the formation, growth, and rupture of IAs; however, its precis...
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40478-024-01756-5 |
| _version_ | 1827309914171637760 |
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| author | Martina Glavan Ana Jelic Damien Levard Juhana Frösen Sara Keränen Bart A. A. Franx Ana-Rita Bras Estelle R. Louet Ádám Dénes Mario Merlini Denis Vivien Marina Rubio |
| author_facet | Martina Glavan Ana Jelic Damien Levard Juhana Frösen Sara Keränen Bart A. A. Franx Ana-Rita Bras Estelle R. Louet Ádám Dénes Mario Merlini Denis Vivien Marina Rubio |
| author_sort | Martina Glavan |
| collection | DOAJ |
| description | Abstract Intracerebral aneurysms (IAs) are pathological dilatations of cerebral arteries whose rupture leads to subarachnoid hemorrhage, a significant cause of disability and death. Inflammation is recognized as a critical contributor to the formation, growth, and rupture of IAs; however, its precise actors have not yet been fully elucidated. Here, we report CNS-associated macrophages (CAMs), also known as border-associated macrophages, as one of the key players in IA pathogenesis, acting as critical mediators of inflammatory processes related to IA ruptures. Using a new mouse model of middle cerebral artery (MCA) aneurysms we show that CAMs accumulate in the IA walls. This finding was confirmed in a human MCA aneurysm obtained after surgical clipping, together with other pathological characteristics found in the experimental model including morphological changes and inflammatory cell infiltration. In addition, in vivo longitudinal molecular MRI studies revealed vascular inflammation strongly associated with the aneurysm area, i.e., high expression of VCAM-1 and P-selectin adhesion molecules, which precedes and predicts the bleeding extent in the case of IA rupture. Specific CAM depletion by intracerebroventricular injection of clodronate liposomes prior to IA induction reduced IA formation and rupture rate. Moreover, the absence of CAMs ameliorated the outcome severity of IA ruptures resulting in smaller hemorrhages, accompanied by reduced neutrophil infiltration. Our data shed light on the unexplored role of CAMs as main actors orchestrating the progression of IAs towards a rupture-prone state. Graphical abstract |
| first_indexed | 2024-04-24T19:50:19Z |
| format | Article |
| id | doaj.art-250903fb87ee47f8a15b4e3395680621 |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-04-24T19:50:19Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-250903fb87ee47f8a15b4e33956806212024-03-24T12:36:53ZengBMCActa Neuropathologica Communications2051-59602024-03-0112112310.1186/s40478-024-01756-5CNS-associated macrophages contribute to intracerebral aneurysm pathophysiologyMartina Glavan0Ana Jelic1Damien Levard2Juhana Frösen3Sara Keränen4Bart A. A. Franx5Ana-Rita Bras6Estelle R. Louet7Ádám Dénes8Mario Merlini9Denis Vivien10Marina Rubio11UNICAEN, INSERM U1237, Etablissement Français du Sang, Physiopathology and Imaging of Neurological Disorders (PhIND), Cyceron, Institut Blood and Brain @ Caen-Normandie (BB@C), PHIND Boulevard Henri Becquerel, Normandie UniversityUNICAEN, INSERM U1237, Etablissement Français du Sang, Physiopathology and Imaging of Neurological Disorders (PhIND), Cyceron, Institut Blood and Brain @ Caen-Normandie (BB@C), PHIND Boulevard Henri Becquerel, Normandie UniversityUNICAEN, INSERM U1237, Etablissement Français du Sang, Physiopathology and Imaging of Neurological Disorders (PhIND), Cyceron, Institut Blood and Brain @ Caen-Normandie (BB@C), PHIND Boulevard Henri Becquerel, Normandie UniversityHemorrhagic Brain Pathology Research Group, Kuopio University Hospital and AIV Institute for Molecular Medicine, University of Eastern FinlandHemorrhagic Brain Pathology Research Group, Kuopio University Hospital and AIV Institute for Molecular Medicine, University of Eastern FinlandTranslational Neuroimaging Group, Center for Image Sciences, University Medical Center Utrecht and Utrecht University“Momentum” Laboratory of Neuroimmunology, Institute of Experimental MedicineUNICAEN, INSERM U1237, Etablissement Français du Sang, Physiopathology and Imaging of Neurological Disorders (PhIND), Cyceron, Institut Blood and Brain @ Caen-Normandie (BB@C), PHIND Boulevard Henri Becquerel, Normandie University“Momentum” Laboratory of Neuroimmunology, Institute of Experimental MedicineUNICAEN, INSERM U1237, Etablissement Français du Sang, Physiopathology and Imaging of Neurological Disorders (PhIND), Cyceron, Institut Blood and Brain @ Caen-Normandie (BB@C), PHIND Boulevard Henri Becquerel, Normandie UniversityUNICAEN, INSERM U1237, Etablissement Français du Sang, Physiopathology and Imaging of Neurological Disorders (PhIND), Cyceron, Institut Blood and Brain @ Caen-Normandie (BB@C), PHIND Boulevard Henri Becquerel, Normandie UniversityUNICAEN, INSERM U1237, Etablissement Français du Sang, Physiopathology and Imaging of Neurological Disorders (PhIND), Cyceron, Institut Blood and Brain @ Caen-Normandie (BB@C), PHIND Boulevard Henri Becquerel, Normandie UniversityAbstract Intracerebral aneurysms (IAs) are pathological dilatations of cerebral arteries whose rupture leads to subarachnoid hemorrhage, a significant cause of disability and death. Inflammation is recognized as a critical contributor to the formation, growth, and rupture of IAs; however, its precise actors have not yet been fully elucidated. Here, we report CNS-associated macrophages (CAMs), also known as border-associated macrophages, as one of the key players in IA pathogenesis, acting as critical mediators of inflammatory processes related to IA ruptures. Using a new mouse model of middle cerebral artery (MCA) aneurysms we show that CAMs accumulate in the IA walls. This finding was confirmed in a human MCA aneurysm obtained after surgical clipping, together with other pathological characteristics found in the experimental model including morphological changes and inflammatory cell infiltration. In addition, in vivo longitudinal molecular MRI studies revealed vascular inflammation strongly associated with the aneurysm area, i.e., high expression of VCAM-1 and P-selectin adhesion molecules, which precedes and predicts the bleeding extent in the case of IA rupture. Specific CAM depletion by intracerebroventricular injection of clodronate liposomes prior to IA induction reduced IA formation and rupture rate. Moreover, the absence of CAMs ameliorated the outcome severity of IA ruptures resulting in smaller hemorrhages, accompanied by reduced neutrophil infiltration. Our data shed light on the unexplored role of CAMs as main actors orchestrating the progression of IAs towards a rupture-prone state. Graphical abstracthttps://doi.org/10.1186/s40478-024-01756-5CNS-associated macrophagesIntracerebral aneurysmsMiddle cerebral arteryVascular inflammationMRI |
| spellingShingle | Martina Glavan Ana Jelic Damien Levard Juhana Frösen Sara Keränen Bart A. A. Franx Ana-Rita Bras Estelle R. Louet Ádám Dénes Mario Merlini Denis Vivien Marina Rubio CNS-associated macrophages contribute to intracerebral aneurysm pathophysiology Acta Neuropathologica Communications CNS-associated macrophages Intracerebral aneurysms Middle cerebral artery Vascular inflammation MRI |
| title | CNS-associated macrophages contribute to intracerebral aneurysm pathophysiology |
| title_full | CNS-associated macrophages contribute to intracerebral aneurysm pathophysiology |
| title_fullStr | CNS-associated macrophages contribute to intracerebral aneurysm pathophysiology |
| title_full_unstemmed | CNS-associated macrophages contribute to intracerebral aneurysm pathophysiology |
| title_short | CNS-associated macrophages contribute to intracerebral aneurysm pathophysiology |
| title_sort | cns associated macrophages contribute to intracerebral aneurysm pathophysiology |
| topic | CNS-associated macrophages Intracerebral aneurysms Middle cerebral artery Vascular inflammation MRI |
| url | https://doi.org/10.1186/s40478-024-01756-5 |
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