Monoclonal antibodies preventing leukocyte activation reduce experimental neurologic injury and enhance efficacy of thrombolytic therapy.

Abstract

We evaluated the ability of monoclonal antibodies directed against leukocyte adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], CD18) to enhance the efficacy of thrombolysis in a rabbit cerebral embolism stroke model. Both tissue-type plasminogen activator (tPA) and anti-CD18 (alpha-CD18) monoclonal antibody administered 5 minutes after embolization increased the quantity of clots required to produce neurologic damage, although the combination was no more effective than either substance alone. Neither alpha-CD18 nor anti-ICAM-1 (alpha-ICAM-1) improved neurologic outcome at postischemic delays of 15 or 30 minutes. However, the combination of alpha-ICAM-1 (15 minutes after embolization) and tPA (2 hours after embolization) significantly improved neurologic outcome even though neither substance was effective alone at these postembolization delays. These findings suggest that prevention of leukocyte adhesion increases the postischemic duration at which thrombolytic therapy remains effective.

• Authors: M P Bowes, R Rothlein, S C Fagan, J A Zivin
• Journal: Neurology (Neurology) Vol. 45 Issue 4 Pg. 815-9 (Apr 1995) ISSN: 0028-3878 [Print] United States
• PMID: 7723976 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Intercellular Adhesion Molecule-1
• Tissue Plasminogen Activator

Topics

• Animals
• Antibodies, Monoclonal (therapeutic use)
• Brain Ischemia (drug therapy, therapy)
• Cell Adhesion (immunology)
• Combined Modality Therapy
• Disease Models, Animal
• Intercellular Adhesion Molecule-1 (immunology)
• Leukocytes (immunology)
• Rabbits
• Thrombolytic Therapy
• Tissue Plasminogen Activator (therapeutic use)