Role of cell adhesion molecules in brain injury after transient middle cerebral artery occlusion in the rat.
Activated neutrophils appear to be directly involved in tissue injury after focal cerebral ischemia and reperfusion. Intercellular adhesion molecules-1 (ICAM-1) and CD11/CD18 integrins have been implicated in ischemia-reperfusion induced neutrophil endothelial adhesion and transmigration. We therefore investigated the roles of CD11a/CD18 (LFA-1) and ICAM-1 in cerebral ischemia-reperfusion injury by using monoclonal antibodies, WT1 (anti-CD11a), WT3 (anti-CD18), and 1A29 (anti-ICAM-1). Rats were subjected to 1 h of middle cerebral artery occlusion (MCAO). Individual antibodies were administered at a dose of 5 mg/kg intraperitoneally at 15 min before ischemia and immediately after reperfusion. Rats were killed at 24 h after reperfusion, and brain edema, neutrophil infiltration and infarct size were measured. Sustained enhancement of ICAM-1 expression on capillaries was observed up to 24 h (beginning between 1 and 3 h after reperfusion). While, leukocytes began to infiltrate into the ischemic hemisphere between 6 and 12 h after reperfusion. Treatment with individual antibodies against cell adhesion molecules reduced edema formation and infarct size in addition to neutrophil accumulation 24 h after reperfusion. These results strongly implicate the invasion of neutrophils in the development of post-ischemic brain injury, and suggest that interactions between CD11a/CD18 and ICAM-1 contribute to neutrophil infiltration into the ischemic brain.
Matsuo
Y
Y
Kanzakigawa Laboratory, Shionogi Research Laboratories, Shionogi & Co., LTD., Osaka, Japan.
Onodera
H
H
Shiga
Y
Y
Shozuhara
H
H
Ninomiya
M
M
Kihara
T
T
Tamatani
T
T
Miyasaka
M
M
Kogure
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001929:Brain Edema / Q000473:pathology; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D002536:Cerebral Arteries / Q000502:physiology; D002544:Cerebral Infarction / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology
D000911:Antibodies, Monoclonal; D015816:Cell Adhesion Molecules, Neuronal; D009195:Peroxidase