ANTIBODIES AGAINST ADHESION MOLECULES REDUCE APOPTOSIS AFTER TRANSIENT MIDDLE CEREBRAL-ARTERY OCCLUSION IN RAT-BRAIN

We tested the hypothesis that treatment of transient focal cerebral is chemia in rat with antibodies directed against adhesion molecules redu ces apoptosis. Rats (n = 31) were subjected to 2 h of middle cerebral artery (MCA) occlusion induced by intraluminal insertion of a nylon mo nofilament into the internal carotid artery, Upon reperfusion, animals were treated with monoclonal antibodies directed against intercellula r adhesion molecule (ICAM)-1) (n = 8) or integrin CD11b/CD18 (n = 10), or administered IgG1 as a control (n = 13). At 48 h after ischemia, a nimals were killed and the brains analyzed for ischemic cell damage, u sing hematoxylin and eosin (H/E); apoptosis, using the terminal deoxyn ucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (T UNEL) method; and inflammatory cells, using immunohistochemistry with an anti-myeloperoxidase (MPO) antibody. Data revealed a significant re duction in the volume of infarction (p < 0.01) and a decline in the ab solute (p < 0.001), and normalized (to the ischemic area, p < 0.05) nu mbers of apoptotic cells in both animals treated with anti-ICAM-1 and anti-CD11b antibodies compared to control animals. The numbers of immu noreactive MPO cells were also reduced in the treatment groups compare d to those in the control group (p < 0.05). These data suggest that tr eatment with anti-adhesion molecule antibodies selectively reduce apop tosis, and that a contributing factor to the beneficial effect of anti body treatment for reducing ischemic cell damage may be a reduction in numbers of apoptotic cells.