Anti-CD11b monoclonal antibody reduces ischemic cell damage after transient focal cerebral ischemia in rat.
We investigated the effect of an anti-CD11b monoclonal antibody (1B6c) on ischemic cell damage after transient middle cerebral artery occlusion. We divided animals into three groups: MAb 1 group (n = 5)--rats were subjected to 2 hours of transient occlusion and 1B6c (1 mg/kg) was administered intravenously at 0 and 22 hours of reperfusion; MAb 2 group (n = 5)--same experimental protocol as MAb 1 group, except that the initial dose of 1B6c was increased to 2 mg/kg; and control group (n = 5)--same experimental protocol as MAb 2 group, except that an isotype-matched control antibody was administered. Animals were weighed and tested for neurological function before and after occlusion of the middle cerebral artery. Forty-six hours after reperfusion, brain sections were stained with hematoxylin and eosin for histology evaluation. We observed a significant reduction of weight loss and improvement in neurological function after ischemia in the MAb 2 animals compared to MAb 1 and vehicle-treated animals (p < 0.05). The lesion volume was significantly smaller in the MAb 2 group (19.5 +/- 1.9%) compared to MAb 1 (29.9 +/- 2.6%) and vehicle-treated (34.2 +/- 5.4%) groups (p < 0.01). Tissue polymorphonuclear cell numbers were reduced in both 1B6c-administered groups. Our data demonstrate that administration of anti-CD11b antibody results in a dose-dependent, significant functional improvement and reduction of ischemic cell damage after transient focal cerebral ischemia in the rat.
Chen
H
H
Department of Neurology, Henry Ford Hospital, Detroit, MI 48202.
Chopp
M
M
Zhang
R L
RL
Bodzin
G
G
Chen
Q
Q
Rusche
J R
JR
Todd
R F
RF
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000502:physiology; D001921:Brain / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D016177:Macrophage-1 Antigen / Q000276:immunology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000911:Antibodies, Monoclonal; D016177:Macrophage-1 Antigen