Cerebral ischemia is accompanied by a marked inflammatory reaction that is initiated by ischemia-induced expression of cytokines, adhesion molecules, and other inflammatory mediators, including prostanoids and nitric oxide. Preclinical studies suggest that interventions that are aimed at attenuating such inflammation reduce the progression of brain damage that occurs during the late stages of cerebral ischemia. In particular, strategies that block the activity of inflammation-related enzymes, such as inducible nitric oxide synthase and cyclo-oxygenase-2, reduce ischemic damage with an extended therapeutic window. Although a clinical trial using murine antibodies against intercellular adhesion molecule-1 did not show benefit in patients with ischemic stroke, recent data indicate that immune activation induced by the heterologous protein may have played an important role in the failure of this trial. Therefore, there is a strong rationale for continuing to explore the efficacy of anti-inflammatory therapies in the treatment of the late stages of cerebral ischemia.
Center for Clinical and Molecular Neurobiology, Department of Neurology, University of Minnesota, Minneapolis, Minnesota, USA
Correspondence to C. Iadecola, M.D., University of Minnesota Medical School, Department of Neurology, Box 295 UMHC, 420 Delaware Street S.E., Minneapolis, MN 55455, USA. Tel: +1 612 624 1902; fax: +1 612 625 7950; e-mail: email@example.com
Abbreviations COX: cyclo-oxygenase ICAM: intercellular adhesion molecule iNOS: inducible nitric oxide synthase MCA: middle cerebral artery NO: nitric oxide TNF: tumor necrosis factor