Mannose binding lectin modulates cerebral injury after ischemic stroke and reperfusion

Abstract

Complement proteins mediate reperfusion injury via cytolysis, opsonin, and inflammatory processes. The presence of mannose binding lectin (MBL), necessary for lectin pathway complement activation, is known to increase tissue damage in murine models of myocardial, intestinal, and renal ischemia-reperfusion injury. We investigated the potential protective role of MBL deficiency in cerebral injury after ischemic stroke and reperfusion. Congenic mice with targeted mutations to MBL genes (MBL−/−) or the C57Bl/6 strain (MBL+/+) were subjected to sixty minutes of cerebral ischemia and 24 hours of reperfusion using the intraluminal filament method. After twenty-four hours of reperfusion, the brains were removed, sliced in 2mm sections, and stained with 1% triphenyltetrazolium chloride for analysis of cerebral infarct volume and hemispheric edema. MBL deficiency significantly decreased cerebral infarct volume in the striatum (p < 0.05) but not in the cortex or total hemisphere. MBL deficiency reduced hemispheric edema by 44%. These results indicate that in a mouse model of ischemic stroke and reperfusion 1) MBL deficiency protects brain striatum and 2) MBL may play a role in edema formation. Elucidating mechanisms of MBL mediated striatal neuroprotection and reduced hemispheric edema will add to the understanding of complement-mediated reperfusion injury after stroke. Supported by NIH NRSA 1F31 NR010658-01 (Morrison)