The combination of lamotrigine and mild hypothermia prevents ischemia-induced increase in hippocampal glutamate

The excessive release of glutamate during cerebral ischemia may play an imp ortant role in subsequent neuronal injury. Both lamotrigine and hypothermia have independently been shown to attenuate the release of glutamate, In th is study, the authors sought to determine whether these effects were additi ve. Thirty-five New Zealand White rabbits were randomized to one of six gro ups: a normothermic control group; a lamotrigine-treated group: two hypothe rmic groups at 33 degreesC or 34.5 degreesC; or two groups treated with bot h hypothermia at 33 degreesC or 34.5 degreesC plus lamotrigine. Animals wer e anesthetized before implanting microdialysis probes in the hippocampus. E sophageal temperature was maintained at 38 degreesC in the control and lamo trigine groups, while the temperatures of animals in the hypothermia and hy pothermia-plus-lamotrigine groups were cooled to 33 degreesC or 34.5 degree sC. Two 10 minute periods of global cerebral ischemia were produced by infl ating a neck tourniquet. Levels of glutamate in the microdialysate were the n determined using high-performance liquid chromatography. Extracellular gl utamate concentrations increased only slightly from baseline during the fir st ischemic period. Glutamate levels during the second ischemic episode in the hypothermia-plus-lamotrigine group (34.5 degreesC) were significantly l ower than those in the hypothermia group alone (34.5 degreesC), lamotrigine , or control groups (P < .01). The fact that mild hypothermia (34.5<degrees >C) plus lamotrigine (20 mg/kg) together were more effective in inhibiting extracellular glutamate accumulation than hypothermia (34.5 degreesC) or la motrigine (20 mg/kg) alone, suggests the potential for increased neuroprote ction by the addition of lamotrigine to mild hypothermia.