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Propranolol Reduces...
Propranolol Reduces the Development of Lesions and Rescues Barrier Function in Cerebral Cavernous Malformations : A Preclinical Study
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- Oldenburg, Joppe (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Malinverno, Matteo (author)
- FIRC Inst Mol Oncol Fdn, Vasc Biol Unit, Milan, Italy.
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- Globisch, Maria A. (author)
- Uppsala universitet,Vaskulärbiologi
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- Maderna, Claudio (author)
- FIRC Inst Mol Oncol Fdn, Vasc Biol Unit, Milan, Italy.
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- Corada, Monica (author)
- FIRC Inst Mol Oncol Fdn, Vasc Biol Unit, Milan, Italy.
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- Orsenigo, Fabrizio (author)
- FIRC Inst Mol Oncol Fdn, Vasc Biol Unit, Milan, Italy.
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- Conze, Lei Liu (author)
- Uppsala universitet,Vaskulärbiologi
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- Rorsman, Charlotte (author)
- Uppsala universitet,Vaskulärbiologi
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- Sundell, Veronica (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Arce, Maximiliano (author)
- Uppsala universitet,Vaskulärbiologi
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- Smith, Ross O. (author)
- Uppsala universitet,Vaskulärbiologi
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- Yau, Anthony C. Y. (author)
- Uppsala universitet,Vaskulärbiologi
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- Hulsart Billström, Gry, 1982- (author)
- Uppsala universitet,Ortopedi
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- Öhman, Caroline (author)
- Uppsala universitet,Tillämpad materialvetenskap
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- Beznoussenko, Galina, V (author)
- FIRC Inst Mol Oncol Fdn, Vasc Biol Unit, Milan, Italy.;FIRC Inst Mol Oncol Fdn, Elect Microscop Lab, Milan, Italy.
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- Mironov, Alexander A. (author)
- FIRC Inst Mol Oncol Fdn, Elect Microscop Lab, Milan, Italy.
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- Fernando, Dinesh (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Skogens biomaterial och teknologi,Department of Forest Biomaterials and Technology,Swedish Univ Agr Sci, Dept Biomat & Technol Wood Sci, Uppsala, Sweden.
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- Daniel, Geoffrey (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Skogens biomaterial och teknologi,Department of Forest Biomaterials and Technology,Swedish Univ Agr Sci, Dept Biomat & Technol Wood Sci, Uppsala, Sweden.
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- Olivari, Davide (author)
- Inst Ric Farmacol Mario Negri IRCCS, Cardiopulm Physiopathol Lab, Cardiovasc Med Dept, Milan, Italy.
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- Fumagalli, Francesca (author)
- Inst Ric Farmacol Mario Negri IRCCS, Cardiopulm Physiopathol Lab, Cardiovasc Med Dept, Milan, Italy.
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- Lampugnani, Maria Grazia (author)
- FIRC Inst Mol Oncol Fdn, Vasc Biol Unit, Milan, Italy.;Mario Negri Inst Pharmacol Res, Milan, Italy.
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- Dejana, Elisabetta (author)
- Uppsala universitet,Vaskulärbiologi,FIRC Inst Mol Oncol Fdn, Vasc Biol Unit, Milan, Italy.;Univ Milan, Sch Med, Dept Oncol & Haematooncol, Milan, Italy.
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- Magnusson, Peetra (author)
- Uppsala universitet,Vaskulärbiologi
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(creator_code:org_t)
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- Lippincott Williams & Wilkins, 2021
- 2021
- English.
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In: Stroke. - : Lippincott Williams & Wilkins. - 0039-2499 .- 1524-4628. ; 52:4, s. 1418-1427
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://res.slu.se/i...
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Abstract
Subject headings
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- Background and Purpose: Cerebral cavernous malformations (CCM) present as mulberry-like malformations of the microvasculature of the central nervous system. Current medical treatment of CCM lesions is limited to surgical removal of the vascular malformations. It is, therefore, important to identify therapeutic drug treatments for patients with CCM. Propranolol has shown great benefit in the treatment of infantile hemangioma. In addition, patients with CCM who receive propranolol have demonstrated a reduction of their lesions. Our investigation set out to provide preclinical data to support propranolol as a therapeutic treatment.Methods: An inducible endothelial-specific Ccm3 knockout murine model (CCM3(iECKO)) was used, with assessment of lesion quantity and size following oral treatment with propranolol. Scanning and transmission electron microscopy were used to characterize the CCM3(iECKO) lesions and the effects of propranolol on the disease. Immunofluorescent imaging was used to investigate pericyte coverage in the propranolol-treated CCM3(iECKO) mice.Results: With propranolol treatment, the lesion quantity, size, and volume decreased in both the brain and retina in the CCM3(iECKO) model. Novel characteristics of the CCM3(iECKO) lesions were discovered using electron microscopy, including plasmalemmal pits and thickening of the endothelial-pericyte basal membrane. These characteristics were absent with propranolol treatment. Pericyte coverage of the CCM3(iECKO) lesions increased after propranolol treatment, and vascular leakage was reduced.Conclusions: This study supports the concept that propranolol can be used to reduce and stabilize vascular lesions and can, therefore, be suggested as a pharmaceutical treatment for CCM.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- cavernous
- central nervous system
- endothelial cells
- pericytes
- propranolol
- vascular malformations
Publication and Content Type
- ref (subject category)
- art (subject category)
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Stroke
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- By the author/editor
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Oldenburg, Joppe
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Malinverno, Matt ...
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Globisch, Maria ...
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Maderna, Claudio
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Corada, Monica
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Orsenigo, Fabriz ...
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show more...
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Conze, Lei Liu
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Rorsman, Charlot ...
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Sundell, Veronic ...
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Arce, Maximilian ...
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Smith, Ross O.
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Yau, Anthony C. ...
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Hulsart Billströ ...
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Öhman, Caroline
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Beznoussenko, Ga ...
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Mironov, Alexand ...
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Fernando, Dinesh
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Daniel, Geoffrey
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Olivari, Davide
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Fumagalli, Franc ...
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Lampugnani, Mari ...
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Dejana, Elisabet ...
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Magnusson, Peetr ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Neurology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
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Stroke
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Uppsala University
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Swedish University of Agricultural Sciences