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 sacrificed at 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.