The effects of FK506 on neurologic and histopathologic outcome after transient spinal cord ischemia induced by aortic cross-clamping in rats

Spinal cord injury is a devastating complication of thoracoabdominal aortic surgery. We investigated the effect of the immunosuppressant FK506, a macr olide antibiotic demonstrated to have neuroprotective effects in cerebral i schemia models, in a rat model of transient spinal cord ischemia. Spinal co rd ischemia was induced in anesthetized rats by using direct aortic arch pl us left: subclavian artery cross-clamping through a limited thoracotomy. Ex perimental groups were as follows: sham-operation; control, receiving only vehicle; FK506 A, receiving FK506 (1 mg/kg TV) before clamping; and FK506 B , receiving FK506 (1 mg/kg IV) at the onset of reperfusion. Neurologic stat us was assessed at 24 h and then daily up to 96 h with a 0 to 6 scale (0, n ormal function; 6, severe paraplegia). Rats were randomly killed at 24, 48, or 96 h, and spinal cords were harvested for histopathology. Physiologic v ariables did not differ significantly among experimental groups. All contro l rats suffered severe and definitive paraplegia. FK506-treated rats had si gnificantly better neurologic outcome compared with control. Histopathologi c analysis disclosed severe injury in the lumbar gray matter of all control rats, whereas most FK506-treated rats had less injury. These data suggest that FK506 can improve neurologic recovery and attenuate spinal cord injury induced by transient thoracic aortic cross-clamping.