INTERCELLULAR-ADHESION MOLECULE-1-DEFICIENT MICE ARE LESS SUSCEPTIBLETO CEREBRAL-ISCHEMIA - REPERFUSION INJURY

Neutrophil emigration is mediated by adhesion proteins that are highly expressed on the endothelial surface during inflammatory processes in the brain. Intercellular adhesion molecule-1 (CAM-1) is an inducible adhesion molecule that binds to leukocyte integrins and facilitates ne utrophil adhesion and transendothelial migration. To study the role of ICAM-1 during ischemia and reperfusion in the brain, we analyzed the effect of transient focal cerebral ischemia in ICAM-1-deficient mice g enerated by gene targeting in embryonic stem cells. Transient focal is chemia was induced by occluding the left middle cerebral artery for 3 hours followed by a 21- or 45-hour reperfusion period. When compared w ith their wild-type littermates, ICAM-1-deficient mice were less susce ptible to cerebral injury as demonstrated by a 5.6- or 7.8-foid reduct ion in infarction volume, respectively. These data support the premise that neutrophil adhesion in ischemic areas may be deleterious and tha t ICAM-1 deficiency reduces neurological damage after transient focal cerebral ischemia.