Neuroprotective Effects of Lamotrigine in Transient Global Ischemia

ABSTRACT

BACKGROUND AND PURPOSE: Current therapy for acute ischemic stroke is highly focused on neuroprotective agents, and many ion channel blockers have been challenged for experimental models. In this study, we tried to reveal the neuroprotective effect of lamotrigine, a voltage-sensitive sodium channel blocker, for transient global ischemia of Mogolian gerbil. METHODS: Lamotrigine (50mg/kg) was administered via gastric tube 30 minutes before and after global ischemia (for 10 min) under body temperature monitoring. Sham-operated and non-treated ischemia group were compared. Seven days after reperfusion, gerbils were killed with perfusion/fixation technique and representative sections were cut through the hippocampus. Hematoxylin-Eosin staining was done for microscopic examination and number of viable neurons in CA1 area was counted. RESULTS: Neuronal density was different between sham-operated (n=11), non-treated ischemic (n=11), and lamotrigine-treated (n=26) group (107.8+13.1/mm vs. 21.5+23.0/mm vs. 82.0+13.1/mm, p<0.01). Both pre-(n=17) and post-treated group (n=9) showed significant neuroprotective effect compared with non-treated group. Neuronal density of pre-treated group was slightly higher than in post-treated group, though statistically not significant (84.6+13.0/mm vs. 77.3+12.7/mm, p=0.13). CONCLUSION: These results show that lamotrigine may have some effects reducing the delayed neuronal death in transient global ischemia. Considering the mechanism of action, we suggest that activation of voltage-sensitive sodium channel and release of glutamate at early phase of ischemia may be related to the delayed neuronal death.