Inhibition of Beta2 Integrin-mediated Leukocyte Adhesion Attenuates the Inflammatory Response and is Neuroprotective Following Global Cerebral Ischemia

Leukocyte adhesion to cerebral endothelial cells plays a critical role in the inflammatory response following transient global cerebral ischemia but its contribution to delayed neuronal cell death is not completely understood. We compared ischemic mice treated with a monoclonal antibody to β2-integrin adhesion receptors (anti-CD18) or a non-binding control antibody following ischemia. Inflammation was characterized by increased CD18 expression on leukocytes and inflammatory mediators in the peripheral blood and brain tissue. Notably, interleukin-1β, which has been shown to mediate cell death in neurons, was elevated in the blood and brain. Anti-CD18 blocked leukocyte adhesion as well as the inflammatory responses, including interleukin-1β expression in neurons. Blocking leukocyte adhesion protected the structural integrity of the hippocampus, cerebral cortex and thalamus, and preserved spatial. Leukocytes adhesion to endothelial cells plays an important role in the evolution of neurological deficit in global cerebral ischemia despite the lack of transmigration of leukocytes across blood-brain-barrier.MAS