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

Brain Res. 1994 Sep 12;656(2):344-52. 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.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • Body Water / metabolism
  • Brain / metabolism*
  • Brain / pathology
  • Brain Edema / pathology
  • Cell Adhesion Molecules, Neuronal / biosynthesis
  • Cell Adhesion Molecules, Neuronal / immunology
  • Cell Adhesion Molecules, Neuronal / physiology*
  • Cerebral Arteries / physiology
  • Cerebral Infarction / pathology
  • Endothelium, Vascular / metabolism
  • Immunohistochemistry
  • Ischemic Attack, Transient / metabolism*
  • Ischemic Attack, Transient / pathology
  • Male
  • Neutrophils / physiology
  • Peroxidase / metabolism
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / pathology


  • Antibodies, Monoclonal
  • Cell Adhesion Molecules, Neuronal
  • Peroxidase