title: Role of cell adhesion molecules in brain injury after transient middle cerebral artery occlusion in the rat.
abstract: 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.
authors: Kanzakigawa Laboratory, Shionogi Research Laboratories, Shionogi & Co., LTD., Osaka, Japan.
authors: Y
authors: Y
authors: Matsuo
authors: H
authors: H
authors: Onodera
authors: Y
authors: Y
authors: Shiga
authors: H
authors: H
authors: Shozuhara
authors: M
authors: M
authors: Ninomiya
authors: T
authors: T
authors: Kihara
authors: T
authors: T
authors: Tamatani
authors: M
authors: M
authors: Miyasaka
authors: K
authors: K
authors: Kogure
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D015816:Cell Adhesion Molecules, Neuronal; D009195:Peroxidase