(Stroke. 2001;32:206.)
© 2001 American Heart Association, Inc.
Original Contributions |
Antibody to the 
4 Integrin Decreases Infarct Size in Transient Focal Cerebral Ischemia in Rats
From the University of Washington School of Medicine, Seattle, and Biogen Inc, Cambridge, Mass (J.R.).
Correspondence to Kyra Becker, MD, Box 359775, Harborview Medical Center, 325 Ninth Ave, Seattle, WA 98104-2499. E-mail kjb{at}u.washington.edu
Background and Purpose—Inflammation, a process that involves neutrophils, lymphocytes, and monocytes, contributes to cerebral ischemic injury. Blockade 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 occlusion followed by 45
hours of reperfusion. Two hours after the onset of ischemia,
one group of animals received an intraperitoneal
injection of antibodies to the 
4 integrin
(n=16); another group was injected with an isotype control antibody
(n=11). Neurological examination, body temperature, and body weight
were assessed at different time points after stroke. Animals were
killed 48 hours after the onset of ischemia for determination
of infarct 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 animals
treated with anti-4 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. Peripheral blood leukocyte counts
were significantly higher in anti-4–treated
animals (6.8±2.2x109 versus
2.9±1.9x109;
P=0.001) and revealed 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 antibodies to
4 (120.1±51.21 versus 173.7±42.29
mm3;
P=0.012).
Conclusions—These data
support a role for lymphocytes and monocytes in cerebral
ischemic injury and show that blockade of
4, even when instituted after the onset of
ischemia, can improve neurological outcome and decrease infarct
volume.
Editorial Comment
Departments of Neurosurgery, Neurology, and, Neurological Sciences, Stanford University Medical Center, Stanford, California
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