title: The contribution of mannose binding lectin to reperfusion injury after ischemic stroke.
abstract: After complement system (CS) activation, the sequential production of complement products increases cell injury and death through opsonophagocytosis, cytolysis, adaptive, and inflammatory cell responses. These responses potentiate cerebral ischemia-reperfusion (IR) injury after ischemic stroke and reperfusion. Activation of the CS via mannose binding lectin (MBL)-initiated lectin pathway is known to increase tissue damage in response to IR in muscle, myocardium and intestine tissue. In contrast, the contribution of this pathway to cerebral IR injury, a neutrophil-mediated event, is less clear. Therefore, we investigated the potential protective role of MBL deficiency in neutrophil-mediated cerebral injury after IR. Using an intraluminal filament method, neutrophil activation and cerebral injury were compared between MBL-deficient and wild type C57Bl/6 mice subjected to 60 minutes of MCA ischemia and reperfusion. Systemic neutrophil activation was not decreased in MBL-deficient animals after IR. In MBL-deficient animals, cerebral injury was significantly decreased only in the striatum (p < 0.05). Despite MBL deficiency, C3 depositions were evident in the injured hemisphere during reperfusion. These results indicate that while MBL deficiency results in a modest protection of a sub-cortical brain region during IR, redundant complement pathway activation may overwhelm further beneficial effects of MBL deficiency during reperfusion.
authors.affiliation: College of Nursing, University of Arizona, Tucson Arizona, USA. hmorrison@mcg.edu
authors.forename: Helena
authors.initials: H
authors.lastname: Morrison
authors.forename: Jennifer
authors.initials: J
authors.lastname: Frye
authors.forename: Grace
authors.initials: G
authors.lastname: Davis-Gorman
authors.forename: Janet
authors.initials: J
authors.lastname: Funk
authors.forename: Paul
authors.initials: P
authors.lastname: McDonagh
authors.forename: Gregory
authors.initials: G
authors.lastname: Stahl
authors.forename: Leslie
authors.initials: L
authors.lastname: Ritter
mesh_terms: D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000235:genetics; D003342:Corpus Striatum / Q000098:blood supply / Q000378:metabolism; D019610:Cytoprotection / Q000235:genetics; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D037601:Mannose-Binding Lectin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics
chemical_list: D037601:Mannose-Binding Lectin