دورية أكاديمية
Targeting Mannose Binding Lectin Confers Long Lasting Protection with a Surprisingly Wide Therapeutic Window in Cerebral Ischemia
| العنوان: | Targeting Mannose Binding Lectin Confers Long Lasting Protection with a Surprisingly Wide Therapeutic Window in Cerebral Ischemia |
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| المؤلفون: | Orsini, Franca, Villa, Pia, Parrella, Sara, Zangari, Rosalia, Zanier, Elisa R., Gesuete, Raffaella, Stravalaci, Matteo, Fumagalli, Stefano, Ottria, Roberta, Reina, José J., Paladini, Alessandra, Micotti, Edoardo, Ribeiro-Viana, Renato, Rojo, Francisco Javier, Pavlov, Vasile I., Stahl, Gregory L., Bernardi, Anna, Gobbi, Marco, Simoni, Maria-Grazia de |
| بيانات النشر: | Lippincott Williams & Wilkins |
| سنة النشر: | 2012 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| الوصف: | Background—The involvement of the complement system in brain injury has been scarcely investigated. Here, we document the pivotal role of mannose-binding lectin (MBL), one of the recognition molecules of the lectin complement pathway, in brain ischemic injury. Methods and Results—Focal cerebral ischemia was induced in mice (by permanent or transient middle cerebral artery occlusion) and rats (by 3-vessel occlusion). We first observed that MBL is deposited on ischemic vessels up to 48 hours after injury and that functional MBL/MBL-associated serine protease 2 complexes are increased. Next, we demonstrated that (1) MBL−/− mice are protected from both transient and permanent ischemic injury; (2) Polyman2, the newly synthesized mannosylated molecule selected for its binding to MBL, improves neurological deficits and infarct volume when given up to 24 hours after ischemia in mice; (3) anti-MBL-A antibody improves neurological deficits and infarct volume when given up to 18 hours after ischemia, as assessed after 28 days in rats. Conclusions—Our data show an important role for MBL in the pathogenesis of brain ischemic injury and provide a strong support to the concept that MBL inhibition may be a relevant therapeutic target in humans, one with a wide therapeutic window of application. ; This study was supported in part by Italian Ministry of Health, Young Investigators Award 2009 (to Dr Zanier), and by Cariplo 2009-2630 - Innovative Materials. Dr Orsini was funded by a fellowship in memory of Amalia Ghezzi. Drs Stahl and Pavlov were funded by National Institutes of Health grants AI089781, HL056086, and HL099130. S. Fumagalli is a fellow of the Monzino Foundation. The authors thank Carlotta Ceriani and Daiana De Blasio for skillful technical assistance and Mauro Tettamanti for statistical advice. ; Peer Reviewed |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0009-7322 |
| العلاقة: | Circulation 126: 1484- 1494 (2012); http://hdl.handle.net/10261/81677Test |
| DOI: | 10.1161/CIRCULATIONAHA.112.103051 |
| الإتاحة: | https://doi.org/10.1161/CIRCULATIONAHA.112.103051Test http://hdl.handle.net/10261/81677Test |
| حقوق: | none |
| رقم الانضمام: | edsbas.FC460603 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00097322 |
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| DOI: | 10.1161/CIRCULATIONAHA.112.103051 |