Riluzole does not attenuate increases in hippocampal glutamate concentrations in a rabbit model of repeated transient global cerebral ischemia

The aim of the present study was to examine the ability of riluzole to inhibit glutamate release during episodes of transient global cerebral ischemia. New Zealand White rabbits (n = 36) were anesthetized with halothane and mechanically ventilated to maintain normocarbia. Microdialysis catheters were inserted bilaterally into the dorsal hippocampus and perfused with artificial cerebrospinal fluid at 2 μL/min. Animals were randomly assigned to control, hypothermia (30°C), or riluzole (2 or 8 mg/kg; R2 and R8) groups. Two episodes of transient global cerebral ischemia (each lasting 10 min) were produced by inflating the pneumatic tourniquet combined with induced hypotension. Dialysate was collected throughout the periischemic period, and glutamate concentrations were determined by using high- performance liquid chromatography. Peak levels were compared by using the Kruskal-Wallis test. Glutamate concentrations significantly increased by twofold to fourfold during the second ischemic period for the control, R2, and R8 groups. Glutamate concentrations in the hypothermic group were significantly lower than those in the other three groups and remained at base-line levels during the entire experiment. This study demonstrates that the sodium channel blocker riluzole does not inhibit ischemia-induced glutamate accumulation. The previously reported neuroprotective ability of riluzole may be caused by mechanisms other than the presynaptic inhibition of glutamate release during ischemia. Implications: Glutamate, an excitatory neurotransmitter, is released in excessive amounts during brain ischemia and may result in neuronal injury and death. Riluzole, a neuronal sodium channel blocker, has neuroprotective properties in some animal models of brain ischemia, possibly because of its ability to inhibit the release of glutamate from synaptic vesicles. However, this microdialysis study failed to demonstrate any attenuation of glutamate release during transient global ischemia after the administration of either 2 mg/kg or 8 mg/kg of riluzole.