MK-801 improves neurological and histological outcomes after spinal cord ischemia induced by transient aortic cross-clipping in rats

Abstract

Background Glutamergic excitotoxicity has been shown to play a deleterious role in the pathophysiology of ischemic spinal cord injury (ISCI). The aim of this study was to investigate the neuroprotective effect of a single dose of MK-801, an antiexcitotoxic drug, in a rat model of ISCI. Methods Ischemic spinal cord injury was induced for 17 minutes in Sprague-Dawley rats using direct aortic arch, just proximal to the left common carotid artery, plus left subclavian artery cross-clamping through a left-sided limited thoracotomy. Study groups were as follows: control group (n = 8) receiving only vehicle and experimental group (n = 8) receiving a single dose of MK-801 (1 mg/kg IV) 10 minutes before aortic clamping. Neurological examination was performed at 6 hours, 24 hours, and daily up to 96 hours. Rats were sacrifice at methylprenisolone socium succinate 96 hours, and spinal cords were removed for histopathology. Results All the control rats had severe permanent neurological deficits after ISCI, whereas the MK-801–treated rats had statistically ( P < .05) better neurological outcome and good recovery. Histopathology revealed severe neuronal necrosis in the lumbar gray matter of control rats, whereas MK-801–treated rats showed mild injury. Conclusion These results demonstrate that combined temporary clipping of the aortic arch (just proximal to the left common carotid artery) plus left subclavian artery for 17 minutes reproduces reliable paraplegia, and a single dose of MK-801 given before ISCI provides significant neuroprotection.