Neuroprotective effects of riluzole and ketamine during transient spinal cord ischemia in the rabbit.
BACKGROUND
Massive release of central excitatory neurotransmitters is an important initial step in ischemic neuronal injury, and modification of this process may provide neuroprotection. We studied the protective effects of the voltage-dependent sodium channel antagonist riluzole and the N-methyl-d-aspartate receptor antagonist ketamine on hind limb motor function and histopathologic outcome in an experimental model of spinal cord ischemia.


METHODS
Temporary spinal cord ischemia was induced by 29 min of infrarenal balloon occlusion of the aorta in 60 anesthetized New Zealand white rabbits. Animals were randomly assigned to one of four treatment groups (n = 15 each): group C, saline (control); group R, riluzole, 8 mg/kg intravenously; group K, ketamine, 55 mg/kg intravenously; group RK, riluzole and ketamine. After reperfusion, riluzole treatment was continued with intraperitoneal infusions. Normothermia (38 degrees C) was maintained during ischemia, and rectal temperature was assessed before and after intraperitoneal infusions. Neurologic function, according to Tarlov's criteria, was evaluated every 24 h, and infarction volume and the number of eosinophilic neurons and viable motoneurons in the lumbosacral spinal cord was evaluated after 72 h.


RESULTS
Neurologic outcome was better in groups R and RK than in groups C and K. All animals in group C (100%) and all animals but one in group K (93%) were paraplegic 72 h after the ischemic insult versus 53% in group R and 67% in group RK (P < 0.01 each). More viable motoneurons were present in groups R and RK than in controls (P < 0.05).


CONCLUSIONS
The data indicate that treatment with riluzole can increase the tolerance of spinal cord motoneurons to a period of normothermic ischemia. Intraischemic ketamine did not provide neuroprotection in this model.
Lips
J
J
Academic Medical Center, University of Amsterdam, The Netherlands.
de Haan
P
P
Bodewits
P
P
Vanicky
I
I
Dzoljic
M
M
Jacobs
M J
MJ
Kalkman
C J
CJ
D000818:Animals; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007238:Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D007649:Ketamine / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010264:Paraplegia / Q000209:etiology / Q000517:prevention & control; D011817:Rabbits; D019782:Riluzole / Q000494:pharmacology*; D013116:Spinal Cord / Q000098:blood supply / Q000473:pathology; D020760:Spinal Cord Ischemia / Q000150:complications / Q000188:drug therapy*
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D007649:Ketamine; D019782:Riluzole