Role of cell adhesion molecules in brain injury after transient middle cerebral artery occlusion in the rat

• Published in: Brain research Vol. 656; no. 2; pp. 344 - 352
• Main Authors: Matsuo, Yoshiyuki, Onodera, Hiroshi, Shiga, Yusei, Shozuhara, Hidetaka, Ninomiya, Mitsuyoshi, Kihara, Tsuyoshi, Tamatani, Takuya, Miyasaka, Masayuki, Kogure, Kyuya
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 12.09.1994; Amsterdam Elsevier; New York, NY
• Subjects: Animals; Antibodies, Monoclonal - therapeutic use; Biological and medical sciences; Body Water - metabolism; Brain - metabolism; Brain - pathology; Brain Edema - pathology; Cell adhesion molecules; Cell Adhesion Molecules, Neuronal - biosynthesis; Cell Adhesion Molecules, Neuronal - immunology; Cell Adhesion Molecules, Neuronal - physiology; Cerebral Arteries - physiology; Cerebral Infarction - pathology; Edema; Endothelium, Vascular - metabolism; Focal cerebral ischemia; Immunohistochemistry; Infarction; Ischemic Attack, Transient - metabolism; Ischemic Attack, Transient - pathology; Male; Medical sciences; Neurology; Neutrophil; Neutrophils - physiology; Peroxidase - metabolism; Rats; Rats, Wistar; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Vascular diseases and vascular malformations of the nervous system; Focal cerebral ischemia; Edema; Infarction; Neutrophil; Cell adhesion molecules; Nervous system diseases; Rat; Rodentia; Central nervous system; Cell adhesion molecule; Gene expression; Vertebrata; Experimental disease; Mammalia; Reperfusion; Ischemia; Animal; Cerebrovascular disease; Brain (vertebrata)
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/0006-8993(94)91478-8

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.