Prevention of ischemic spinal cord injury: Comparative effects of magnesium sulfate and riluzole

Purpose: Excitotoxic mechanisms have been implicated in the pathophysiology of spinal cord ischemic injury induced by aortic cross-damping. We investi gated the effects of the anti-excitotoxic drugs magnesium sulfate (MgSO4) a nd riluzole in a rabbit model of spinal cord ischemia. Method: The infrarenal aorta of New Zealand albino white rabbits (n = 68) w as occluded for 40 minutes. Experimental groups included: a control group, which received only vehicle (n = 17); group A (n = 17), which received rilu zole (8 mg/kg) before clamping; group B (n = 17), which received MgSO4 (100 mg/kg) before damping; and group C (n = 17), which received riluzole (8 mg /kg) and MgSO4 (100 mg/kg) before clamping. Five additional rabbits had the same operation, but did not undergo aortic damping (sham operation). The n eurological status of the rabbits was assessed at 24 hours, 48 hours, and t hen daily for as long as 120 hours by using a modified Tarlov scale. The ra bbits were killed at 24 hours (n = 3 per group), 48 hours (n = 4 per group) , and 120 hours (n = 10 per group) postoperatively. Spinal cords were harve sted for histopathologic and immunohistochemistry examinations for microtub ule-associated protein-2 (MAP-2), a cytoskeletal protein specific from neur ons. Results: No major adverse effect was observed with either riluzole or MgSO4 . All control rabbits became severely paraplegic. All riluzole-treated and MgSO4-treated animals had a better neurological status than control animals . Typical morphological changes characteristic of neuronal necrosis in the gray matter of control animals was demonstrated by means of the histopathol ogical examination, whereas riluzole or magnesium prevented or attenuated n ecrotic phenomenons. Moreover, MAP-2 immunoreactivity was completely lost i n control rabbits, whereas it was preserved, either completely or partially , in rabbits treated with riluzole or magnesium. Riluzole was more effectiv e than MgSO4 in preventing paraplegia caused by motor neuron injury (P < .0 1). Riluzole and MgSO4 had no additive neuroprotective effect. Conclusion: These results demonstrate that riluzole and, to a lesser extent , MgSO4 may afford significant spinal cord protection in a setting of sever e ischemia and may, therefore, be considered for clinical use during "high- risk" operations on the thoracic and thoracoabdominal aorta.