Neurochemical Research

, Volume 43, Issue 8, pp 1599–1607 | Cite as

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

  • Zheng Lin
  • Haoran Lin
  • Wenlu Li
  • Yuwen Huang
  • Haibin Dai
Original Paper


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.


Complement C3 Cerebral ischemia/reperfusion injury TLR2 NFκB Diabetes 



The authors wish to thank Xiuyang Li (Department of Epidemiology & Biostatistics, Zhejiang University School of Medicine) for assistance in the statistical analysis.


This study was supported by the Grants from the National Natural Science Foundation of China (81373391, 81471395, 81573402, 81703479, 81703498 and 81773700), the foundation from the Zhejiang Provincial Natural Science Foundation of China (LY15H310006, LY16H310002 and LY16H310001), the Foundation from Science and Technology Department of Zhejiang Province (2014C33185, 2016C33G2010098), the Health Bureau of Zhejiang Province (2014KYB104, 2014RCA008, and 2016ZDA009). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Compliance with Ethical Standards

Conflict of interest

The authors have declared that no competing interests exist.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina

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