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Review
. 2009:2009:124384.
doi: 10.1155/2009/124384. Epub 2010 Jan 26.

Complement inhibition as a proposed neuroprotective strategy following cardiac arrest

Brad E Zacharia  1 , Zachary L Hickman, Bartosz T Grobelny, Peter A DeRosa, Andrew F Ducruet, E Sander Connolly
Affiliations
Review

Complement inhibition as a proposed neuroprotective strategy following cardiac arrest

Brad E Zacharia et al. Mediators Inflamm. 2009.

Abstract

Out-of-hospital cardiac arrest (OHCA) is a devastating disease process with neurological injury accounting for a disproportionate amount of the morbidity and mortality following return of spontaneous circulation. A dearth of effective treatment strategies exists for global cerebral ischemia-reperfusion (GCI/R) injury following successful resuscitation from OHCA. Emerging preclinical as well as recent human clinical evidence suggests that activation of the complement cascade plays a critical role in the pathogenesis of GCI/R injury following OHCA. In addition, it is well established that complement inhibition improves outcome in both global and focal models of brain ischemia. Due to the profound impact of GCI/R injury following OHCA, and the relative lack of effective neuroprotective strategies for this pathologic process, complement inhibition provides an exciting opportunity to augment existing treatments to improve patient outcomes. To this end, this paper will explore the pathophysiology of complement-mediated GCI/R injury following OHCA.

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Figures

Figure 1
Figure 1
Complement cascade.
See this image and copyright information in PMC

References

    1. Hillmen P, Young NS, Schubert J, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. The New England Journal of Medicine. 2006;355(12):1233–1243. - PubMed
    1. Testa L, Van Gaal WJ, Bhindi R, et al. Pexelizumab in ischemic heart disease: a systematic review and meta-analysis on 15,196 patients. The Journal of Thoracic and Cardiovascular Surgery. 2008;136(4):884–893. - PubMed
    1. Bottiger BW, Motsch J, Braun V, Martin E, Kirschfink M. Marked activation of complement and leukocytes and an increase in the concentrations of soluble endothelial adhesion molecules during cardiopulmonary resuscitation and early reperfusion after cardiac arrest in humans. Critical Care Medicine. 2002;30(11):2473–2480. - PubMed
    1. D’Ambrosio AL, Pinsky DJ, Connolly ES. The role of the complement cascade in ischemia/reperfusion injury: implications for neuroprotection. Molecular Medicine. 2001;7(6):367–382. - PMC - PubMed
    1. Ducruet AF, Hassid BG, MacK WJ, et al. C3a receptor modulation of granulocyte infiltration after murine focal cerebral ischemia is reperfusion dependent. Journal of Cerebral Blood Flow and Metabolism. 2008;28(5):1048–1058. - PubMed

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