Complement Component C3 Promotes Cerebral Ischemia/Reperfusion Injury Mediated by TLR2/NFκB Activation in Diabetic Mice.

Abstract

Complement component C3 (C3), a key factor in the complement system, is heavily involved in various inflammation-associated diseases. However, it remains obscure for its role in the pathogenesis of cerebral ischemia/reperfusion (I/R) injury in diabetes. A transient middle cerebral artery occlusion (tMCAO) model was used for cerebral I/R injury in streptozotocin-induced diabetic mice. Cerebral infarct volume and neurological function were measured at different times of reperfusion. Complement C3 was measured by ELISA and western blotting. It was observed that complement C3 expression was increased in cerebral I/R injury of diabetic mice, whereas complement C3 deficiency abrogated the activation and injury. Furthermore, activating complement C3 promotes TLR2/NFκB activation after I/R injury in diabetic mice, which is inhibited by of the silencing of TLR2. Taken together, our data demonstrate that complement C3 promotes cerebral I/R injury via the TLR2/NFκB pathway in diabetic mice, and regulating the complement C3/TLR2/NFκB pathway may be a novel target for therapeutic intervention in diabetic stroke.