Advances in stroke management

Traditionally, leukocytes of normal function are considered a vital blood element without which the body's survival would be threatened. Leukocytes protect us from invading microorganisms. Without them, we would easily fall prey to the life-threatening attack of otherwise benign infections. In the past few years we have come to realize that as leukocytes react to a variety of tissue injuries, including ischemia, they may actually contribute to and accentuate tissue damage. When tissue injuries such as ischemia occur, signals arise in the endothelium of the microvasculature in the ischemic brain to attract leukocytes to the region of injury. Leukocytes in the circulating blood pass by the vasculature of ischemic brain. They are compelled to linger and attach to the endothelium, flatten, and penetrate the endothelium into the injured ischemic tissue. We now know that there are a variety of receptors on the leukocyte surface that have the ability to react to receptor sites on the endothelium. Among these receptors is the intercellular adhesion molecule-1 (ICAM-1) located on the endothelial cells. Leukocyte adhesion and migration require the interaction of ICAM-1 on the endothelium with CD11/CD18 leukocyte integrins on the surface of neutrophils. As leukocytes and monocytes adhere to the vessel wall, they can release damaging cytokines including IL-1, IL-2, and tissue necrosis factor alpha(TNF-α). These cytokines become proinflammatory and can promote thrombosis by binding circulating anticoagulants, such as protein S, and inhibiting tissue plasminogen activator release.

Some of the early basic observations that led to an understanding of this process grew out of the …