The role of the complement cascade in ischemia/reperfusion injury: Implications for neuroprotection

Background: The complement cascade plays a deleterious role in multiple mod els of ischemia/reperfusion (I/R) injury, including stroke. Investigation o f the complement cascade may provide a critical approach to identifying neu roprotective strategies that can be effective at clinically relevant time p oints in cerebral ischemia. This review of the literature describes the del eterious effects of complement activation in systemic I/R models and previo us attempts at therapeutic complement inhibition, with a focus on the poten tial role of complement inhibition in ischemic neuroprotection. Translation of these concepts into ischemic stroke models and exploration of related n europrotective strategies are also reviewed. Summary of Review: We performed a MEDLINE search to identify any studies pu blished between 1966 and 2001 dealing with complement activation in the set ting of I/R injury. We also searched for studies demonstrating up-regulatio n of any complement components within the central nervous system during inf lammation and/or ischemia. Conclusions: The temporal and mechanistic overlap of the complement cascade with other biochemical events occurring in cerebral I/R injury is quite co mplex and is only beginning to be understood. However, there is compelling evidence that complement is quite active in the setting of acute stroke, su ggesting that anticomplement strategies should be further investigated thro ugh genetic analysis, nonhuman primate models, and clinical investigations.