Plasma-derived and recombinant C1 esterase inhibitor: Binding profiles and neuroprotective properties in brain ischemia/reperfusion injury

C1 esterase inhibitor (C1INH) is known to exert its inhibitory effect by binding several target proteases of the contact and complement systems. One C1INH’s targets comprise mannose-binding lectin (MBL), a critical player in post-stroke pathophysiology. We therefore explored effects recombinant human (rh) plasma derived (pd) C1INH C57BL/6J mice subjected transient occlusion middle cerebral artery (tMCAo), receiving 15 U/mouse pd or rhC1INH intravenously, at reperfusion. analyzed compounds’ (i) neuroprotective effects, (ii) presence, (iii) on circulating brain MBL, (iv) time course endothelial deposition, (v) formation active products. rhC1INH-treated had including reduced behavioral deficits neuronal loss, associated with decreased MBL deposition C4b fragments. In contrast, pdC1INH did not show these despite longer residence time. also response tMCAo C1INH-deficient mice, observing poorer ischemic outcome compared wild type which could be partially prevented administration. conclusion, we that exhibits stronger than corresponding plasma-derived protein after experimental ischemia/reperfusion injury brain, placing it as promising drug for stroke. Differential are likely related more effective inhibition further confirms useful pharmacological