Prevention of ischemic spinal cord injury: comparative effects of magnesium sulfate and riluzole.
OBJECTIVE
Excitotoxic mechanisms have been implicated in the pathophysiology of spinal cord ischemic injury induced by aortic cross-clamping. We investigated the effects of the anti-excitotoxic drugs magnesium sulfate (MgSO(4)) and riluzole in a rabbit model of spinal cord ischemia.


METHODS
The infrarenal aorta of New Zealand albino white rabbits (n = 68) was occluded for 40 minutes. Experimental groups included: a control group, which received only vehicle (n = 17); group A (n = 17), which received riluzole (8 mg/kg) before clamping; group B (n = 17), which received MgSO(4) (100 mg/kg) before clamping; and group C (n = 17), which received riluzole (8 mg/kg) and MgSO(4) (100 mg/kg) before clamping. Five additional rabbits had the same operation, but did not undergo aortic clamping (sham operation). The neurological status of the rabbits was assessed at 24 hours, 48 hours, and then daily for as long as 120 hours by using a modified Tarlov scale. The rabbits 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 harvested for histopathologic and immunohistochemistry examinations for microtubule-associated protein-2 (MAP-2), a cytoskeletal protein specific from neurons.


RESULTS
No major adverse effect was observed with either riluzole or MgSO(4). All control rabbits became severely paraplegic. All riluzole-treated and MgSO(4)-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 histopathological examination, whereas riluzole or magnesium prevented or attenuated necrotic phenomenons. Moreover, MAP-2 immunoreactivity was completely lost in control rabbits, whereas it was preserved, either completely or partially, in rabbits treated with riluzole or magnesium. Riluzole was more effective than MgSO(4) in preventing paraplegia caused by motor neuron injury (P <.01 ). Riluzole and MgSO(4) had no additive neuroprotective effect.


CONCLUSIONS
These results demonstrate that riluzole and, to a lesser extent, MgSO(4) may afford significant spinal cord protection in a setting of severe ischemia and may, therefore, be considered for clinical use during "high-risk" operations on the thoracic and thoracoabdominal aorta.
Lang-Lazdunski
L
L
Departments of Cardiovascular Surgery and Anesthesiology, Hopital Bichat and Xavier Bichat Medical University, Paris, France.
Heurteaux
C
C
Dupont
H
H
Widmann
C
C
Lazdunski
M
M
D000818:Animals; D001011:Aorta; D001013:Aorta, Thoracic / Q000601:surgery; D003250:Constriction; D005260:Female; D007150:Immunohistochemistry; D007511:Ischemia / Q000517:prevention & control*; D008278:Magnesium Sulfate / Q000627:therapeutic use*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010264:Paraplegia / Q000517:prevention & control; D011817:Rabbits; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D019782:Riluzole / Q000627:therapeutic use*; D013116:Spinal Cord / Q000098:blood supply*; D016896:Treatment Outcome
D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D008278:Magnesium Sulfate; D019782:Riluzole