Reduction of central nervous system ischemic injury in rabbits using leukocyte adhesion antibody treatment.
Activated leukocytes appear to be directly involved in ischemic central nervous system injury. A surface glycoprotein (CD18) on the leukocyte is required for endothelial adherence and subsequent function and can be blocked with leukocyte adhesion antibody treatment. We used two animal models to determine the efficacy of anti-CD18 antibody treatment in preserving neurologic function after central nervous system ischemia. We gave a dose of 1 mg/kg anti-CD18 to treatment rabbits 30 minutes before inducing irreversible ischemia in the brain with intraarterial microspheres or in the spinal cord using reversible aortic occlusion. Treatment with anti-CD18 produced a significant reduction in neurologic deficits in the reversible spinal cord model, but not in the irreversible microsphere model. This protective effect supports the active role of leukocytes in central nervous system reperfusion ischemic injury and offers potential for future therapy.
Clark
W M
WM
Department of Neurology, Oregon Health Sciences University, Portland 97201.
Madden
K P
KP
Rothlein
R
R
Zivin
J A
JA
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology*; D018821:CD18 Antigens; D002490:Central Nervous System / Q000098:blood supply*; D004305:Dose-Response Relationship, Drug; D002542:Intracranial Embolism and Thrombosis / Q000150:complications; D007511:Ischemia / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D008297:Male; D008863:Microspheres; D011817:Rabbits; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology; D013116:Spinal Cord / Q000098:blood supply
D000906:Antibodies; D015703:Antigens, CD; D018821:CD18 Antigens; D016028:Receptors, Leukocyte-Adhesion