Evidence for leukocyte infiltration, ICAM-1 expression, permeability following ischemic paraplegia: Functional blocking of ICAM-1 as a new therapeutic target

This study evaluates leukocyte infiltration, ICAM-1 expression, permeability across the blood-spinal cord barrier (BSCB)and therapeutic effect of ICAM-1 following epidural administration. Rabbits weighing ( 2.5 Kg) were anesthetized with halothane, an abdominal incision was made, the descending aorta exposed and occluded with an aneusysm clip. After varible periods of occlusion, the clip was removed and incision closed with sutures and skin clips. Sham-operated controls were prepared identically but descending aorta was not occluded. Following 2,4 and 8h after 30 min occlusion the following were evaluated in the lumbar cord: ICAM-1 expression by immunohistochemistry; leukocyte infiltration by electron microscopy; vascular endothelial permeability across BSCB by radiometry. The therapeutic efficacy of ICAM-1 MAb was tested by preemptive epidural administration of 0.5mg/Kg ICAM-1 MAb, following variable occlusion periods, i.e., 10,15.20,25 and 30 min. The neurological examination was performed 20h later on a Tarlov's scale in a blinded fashion. The ICAM-1 expression and leukocyte recruitment/infiltration were significantly increased following 8h after 30 min occlusion. The BSCB permeability of D-mannitol and inulin was significantly increased. The quantal response curve computed as dichotomous function of non-paraplegia/paraplegia Vs occlusion period based on neurologic evaluation, revealed that treatment with ICAM-1 MAb produced significant reduction in neurological deficits (P<0.05)in this model.