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Title

Mannose-binding lectin promotes local microvascular thrombosis after transient brain ischemia in mice

AuthorsRosa, Xavier de la ; Cervera, Álvaro; Kristoffersen, Anna K.; Valdés, Claudia P.; Varma, Hari M.; Justicia, Carles ; Durduran, Turgut; Chamorro, Ángel; Planas, Anna M.
KeywordsBrain
Infarction
Mannose-binding lectin
Reperfusion
Middle cerebral artery
Complement system proteins
Complement pathway
Issue DateMay-2014
PublisherLippincott Williams & Wilkins
CitationStroke, a journal of cerebral circulation 45(5): 1453-1459 (2014)
AbstractBACKGROUND AND PURPOSE-: Several lines of evidence support the involvement of mannose-binding lectin (MBL) in stroke brain damage. The lectin pathway of the complement system facilitates thrombin activation and clot formation under certain experimental conditions. In the present study, we examine whether MBL promotes thrombosis after ischemia/reperfusion and influences the course and prognosis of ischemic stroke. METHODS-: Middle cerebral artery occlusion/reperfusion was performed in MBL-deficient (n=85) and wild-type (WT; n=83) mice, and the brain lesion was assessed by MRI at days 1 and 7. Relative cerebral blood flow was monitored up to 6 hours after middle cerebral artery occlusion with laser speckle contrast imaging. Fibrin(ogen) was analyzed in the brain vasculature and plasma, and the effects of thrombin inhibitor argatroban were evaluated to assess the role of MBL in thrombin activation. RESULTS-: Infarct volumes and neurological deficits were smaller in MBL knockout mice than in WT mice. Relative cerebral blood flow values during middle cerebral artery occlusion and at reperfusion were similar in both groups, but decreased during the next 6 hours in the WT group only. Also, the WT mice showed more fibrin(ogen) in brain vessels and a better outcome after argatroban treatment. In contrast, argatroban did not improve the outcome in MBL knockout mice. CONCLUSIONS-: MBL promotes brain damage and functional impairment after brain ischemia/reperfusion in mice. These effects are secondary to intravascular thrombosis and impaired relative cerebral blood flow during reperfusion. Argatroban protects WT mice, but not MBL knockout mice, emphasizing a role of MBL in local thrombus formation in acute ischemia/reperfusion. © 2014 American Heart Association, Inc.
Publisher version (URL)http://dx.doi.org/10.1161/STROKEAHA.113.004111
URIhttp://hdl.handle.net/10261/116798
DOI10.1161/STROKEAHA.113.004111
Identifiersdoi: 10.1161/STROKEAHA.113.004111
issn: 1524-4628
Appears in Collections:(IIBB) Artículos
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