The therapeutic effects of epidural intercellular adhesion molecule-1 monoclonal antibody in a rabbit model: involvement of the intercellular adhesion molecule-1 pathway in spinal cord ischemia.
The pathophysiology of ischemia/reperfusion injury involves extravascular migration of leukocytes from the bloodstream to the site of injury. Leukocyte adhesion and intercellular adhesion molecule-1 (ICAM-1) play an important role in the recruitment of leukocytes to the site of injury. In this study, we evaluated the role of the ICAM-1 in spinal cord ischemia and the therapeutic effects of epidural ICAM-1 monoclonal antibody (Mab). The descending aorta was occluded below the renal artery with an aneurysm clip in rabbits anesthetized with halothane. The following variables were evaluated, in addition to ICAM-1 expression in the lumbar spinal cord, in animals receiving saline or ICAM-1 Mab via the epidural route: (1) leukocyte recruitment in the lumen of capillary vessels of the lumbar spinal cord (L6-7) at 8 h after 30 min of aortic occlusion and (2) neurological evaluation at 20 h after aortic occlusion of 10, 15, 17.5, 20, or 25 min. Paraplegia was graded with the following scale: Grade 0, no deficit; Grade 1, partial deficit; and Grade 2, complete paraplegia. Spinal cord ischemia increased the expression of ICAM-1 in the endothelium of spinal cord capillaries and led to capillary leukocyte recruitment and extravascular migration into the lumbar spinal cord parenchyma, which was ablated with epidural ICAM-1 Mab. Epidural ICAM-1 Mab reduced neurological deficits and offered neuroprotection. These findings demonstrate the involvement of the ICAM-1 pathway in spinal cord ischemia and the neuroprotective effects of epidural ICAM-1 Mab. Strategies to ameliorate spinal cord ischemia may entail the administration of leukocyte antiadhesion molecules into the neuraxial space.
Naidu
Kamatham A
KA
Departments of *Neurology, †Anesthesiology, and ‡Physiology, College of Medicine, University of South Florida, Tampa, Florida; and §Oncology Program, H. Lee Moffitt Cancer Center, University of South Florida, Tampa, Florida.
Fu
Eugene S
ES
Sutton
E Truitt
ET
Prockop
Leon D
LD
Cantor
Alan
A
D000210:Acute-Phase Reaction / Q000503:physiopathology; D000783:Aneurysm / Q000503:physiopathology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D016015:Logistic Models; D008297:Male; D010264:Paraplegia / Q000209:etiology; D011817:Rabbits; D013116:Spinal Cord / Q000473:pathology; D020760:Spinal Cord Ischemia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology
D000911:Antibodies, Monoclonal; D018799:Intercellular Adhesion Molecule-1