Arch Hellen Med, 17(5), September-October 2000, 491-505
Inflammatory response after acute stroke
1st Department of Internal Medicine, “G. Gennimatas” General Hospital, Thessaloniki, Greece
Increasingly, data from animal models of cerebral ischemia and preliminary human studies show that inflammatory mechanisms play an important role in secondary neuronal injury after acute cerebral ischemia. Ischemia followed by reperfusion rapidly leads to the expression of inflammatory cytokines, especially TNF-α and IL-1β, which stimulate a cascade of events involving local endothelial cells, neurons, astrocytes, and perivascular cells. This initial release of cytokines is followed by a secondary release of cytokines such as IL-6 and IL-8, an increase in components of the coagulation system, and an up-regulation of cell adhesion molecules. This results in an overabundant recruitment of leucocytes which can decrease perfusion by blocking vessels directly, releasing vasoconstricting substances and killing endothelial cells. Leucocytes cross into the brain, where they degranulate, release cytotoxic enzymes such as myeloperoxidase, and generate oxygen-derived free radicals. Monoclonal antibodies against leucocyte adhesion molecules have been shown to reduce infarct volume in animal models of ischemia-reperfusion, but there are a number of constraints to the application of this therapeutic approach in human acute cerebral ischemia. It is widely expected that increased understanding of the inflammatory and immunologic mechanisms relevant to acute cerebral ischemia will offer more rational and hopeful treatment for acute stroke.
Key words: Αdhesion molecules, Brain ischemia/reperfusion, Cytokines, Inflammation.