¹Experimentelle Neurologie, Charité-Universitätsmedizin Berlin, Berlin, Germany

Correspondence: Dr G Trendelenburg, Experimentelle Neurologie, Department of Neurology, Charité— Universitätsmedizin Berlin, CCM Charitéplatz 1, Berlin D-10117, Germany. E-mail: george.trendelenburg@charite.de

Received 20 March 2007; Revised 14 December 2007; Accepted 17 December 2007; Published online 23 January 2008.

Abstract

Activation of the inflammatory response is a crucial event in the adverse outcome of cerebral ischemia, which is promoted by proinflammatory cytokines such as interleukin (IL)-1. Although caspase-1 is necessary for IL-1 processing, the 'upstream' signaling pathways were, until recently, essentially unknown. Fortunately, the inflammasome, a multiprotein complex responsible for activating caspase-1 and caspase-5, has recently been characterized. The activation of the inflammasome can result in one of several consequences such as cytokine secretion, cell death, or the development of a stress-resistant state. The significance of the inflammasome for the initiation of the inflammatory response during systemic diseases has already been shown and members of the inflammasome complex were recently found to be induced in acute brain injury. However, the specific pathophysiologic role of the inflammasome in neurodegenerative disorders still remains to be clarified. The underlying theories (e.g., danger signal theory) along with the signaling pathways that link the inflammasome to acute neurodegeneration will be discussed here. Furthermore, the stimuli that potentially activate the inflammasome in cerebral ischemia will be specified, as well as their relation to well-known pathways activating the innate immune response (e.g., Toll-like receptor signaling) and the consequences that result from their activation (beneficial versus deleterious).