Article
Characterization of angiogenesis and the neurovascular unit in chronic subdural hematoma
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Authors
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Thomas Wälchli
- Group of CNS Angiogenesis and Neurovascular Link, and Physician-Scientist Program, Swiss Center for Regenerative Medicine and Division of Surgical Research, and Neuroscience Center Zurich and Division of Neurosurgery, University and University Hospital Zurich, and Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland; Division of Neurosurgery, University Hospital Zurich, Zurich, Switzerland; Brain Research Institute, University of Zurich and Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland
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Jan-Karl Burkhardt
- Division of Neurosurgery, University Hospital Zurich, Zurich, Switzerland
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Marian Christoph Neidert
- Division of Neurosurgery, University Hospital Zurich, Zurich, Switzerland
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Luca Regli
- Division of Neurosurgery, University Hospital Zurich, Zurich, Switzerland
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Simon P. Hoerstrup
- Group of CNS Angiogenesis and Neurovascular Link, and Physician-Scientist Program, Swiss Center for Regenerative Medicine and Division of Surgical Research, and Neuroscience Center Zurich and Division of Neurosurgery, University and University Hospital Zurich, and Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland
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Oliver Bozinov
- Division of Neurosurgery, University Hospital Zurich, Zurich, Switzerland
| Published: | June 8, 2016 |
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Outline
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Objective: One hallmark of chronic subdural hematoma (cSDH) is angiogenesis, the growth of blood vessels. However, the underlyning cellular and molecular mechanisms that govern angiogenesis and regulate the neurovascular unit (= endothelial and perivascular cells) in chronic subdural hematoma are poorly understood. Here, we characterize angiogenesis and the neurovascular unit in human chronic subdural hematoma.
Method: Immunofluorescent stainings and confocal microscopy: 40µm coronal tissue sections of human chronic subdural hematoma samples were stained for the endothelial markers CD31, CD105, and VEGFR2, for the tight junction proteins Claudin-5 and Zona occludens, and for the perivascular cell markers PDGFRβ, GFAP, Nestin, and Iba1. Western blot and qRT-PCR: mRNA expression levels of endothelial markers, tight junction proteins as well as of perivascular cell markers were analyzed.
Results: Here, we have characterized angiogenesis and the neurovascular unit of cSDH membrane samples from 10 patients. We found angiogenesis to be highly active, both in the inner and outer membranes of chronic subdural hematoma as well as in the neomembranes that formed in between. Consistent in all 10 human samples, endothelial cells of angiogenic blood vessels showed expression of the classical endothelial markers CD31, CD105, and VEGFR2 as well as of tight junction proteins Claudin-5 and Zona occludens, reminiscent of blood-brain-barrier characteristics. Interestingly, we were also able to detect CD31+ endothelial tip cells - the specialized cell type at the forefront of growing blood vessels. Perivascular cells of the neurovascular unit such as PDGFRβ+ pericytes, GFAP+ astrocytes, Nestin+ neuronal stem cells, and Iba1+ microglia were expressed in the vicinity of angiogenic endothelial tip cells.
Conclusions: In this study, we further characterized angiogenesis and the neurovascular unit in human chronic subdural hematoma samples. Moreover, we were able to detect endothelial tip cells – the specialized cell type at the forefront of growing blood vessels as well as the adjacent cell types of the neurovascular unit. These findings contribute to the understanding of this relevant neurosurgical pathology and may have therapeutic implications in the future. We are currently testing this in a preclinical mouse model.
