The complement cascade as a therapeutic target in intracerebral hemorrhage

Document Type

Article

Abstract

Intracerebral hemorrhage (ICH) is the second most common and deadliest form of stroke. Currently, no pharmacologic treatment strategies exist for this devastating disease. Following the initial mechanical injury suffered at hemorrhage onset, secondary brain injury proceeds through both direct cellular injury and inflammatory cascades, which trigger infiltration of granulocytes and monocytes, activation of microglia, and disruption of the blood-brain barrier with resulting cerebral edema. The complement cascade has been shown to play a central role in the pathogenesis of secondary injury following ICH, although the specific mechanisms responsible for the proximal activation of complement remain incompletely understood. Cerebral injury following cleavage of complement component 3 (C3) proceeds through parallel but interrelated pathways of anaphylatoxin-mediated inflammation and direct toxicity secondary to membrane attack complex-driven erythrocyte lysis. Complement activation also likely plays an important physiologic role in recovery following ICH. As such, a detailed understanding of the variation in functional effects of complement activation over time is critical to exploiting this target as an exciting translational strategy for intracerebral hemorrhage.

Medical Subject Headings

Animals; Cerebral Hemorrhage (physiopathology, therapy); Complement Activation (drug effects); Complement C3 (metabolism); Disease Progression; Humans; Inflammation Mediators (pharmacology, therapeutic use)

Publication Date

10-1-2009

Publication Title

Experimental neurology

E-ISSN

1090-2430

Volume

219

Issue

2

First Page

398

Last Page

403

PubMed ID

19632224

Digital Object Identifier (DOI)

10.1016/j.expneurol.2009.07.018

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