Antibody to the alpha 4 integrin decreases infarct size in transient focalcerebral ischemia in rats

Background and Purpose-Inflammation, a process that involves neutrophils, l ymphocytes, and monocytes, contributes to cerebral ischemic injury. Blockad e of neutrophil adhesion to endothelium improves outcome after experimental stroke. In this study we sought to assess the contribution of lymphocytes and monocytes to ischemic brain injury. Methods-Male Lewis rats underwent 3 hours of middle cerebral artery occlusi on followed by 45 hours of reperfusion, Two hours after the onset of ischem ia, one group of animals received an intraperitoneal injection of antibodie s to the alpha (4) integrin (n=16); another group was injected with an isot ype control antibody (n=11). Neurological examination, body temperature, an d body weight were assessed at different time points after stroke. Animals were killed 48 hours after the onset of ischemia for determination of infar ct volume and leukocyte counts. Results-There were no significant differences in body temperature or weight at any time. Neurological scores (deficits) were significantly less in ani mals treated with anti-or, antibodies at 24 (2.0+/-1.2 versus 3.0+/-0.4; P= 0.006) and 48 (2.0+/-1.2 versus 3.0+/-0.8; P=0.011) hours after ischemia. P eripheral blood leukocyte counts were significantly higher in anti-alpha (4 )-treated animals (6.8+/-2.2X10(9) versus 2.9+/-1.9X10(9); P=0.001) and rev ealed a lymphocyte/monocyte predominance (86.0+/-16.2% versus 71.0+/-15.6%; P=0.008). Infarct volume was significantly less in animals treated with an tibodies to alpha (4) (120.1+/-51.21 versus 173.7+/-42.29 mm(3); P=0.012). Conclusions-These data support a role for lymphocytes and monocytes in cere bral ischemic injury and show that blockade of alpha (4), even when institu ted after the onset of ischemia, can improve neurological outcome and decre ase infarct volume.