백서의 일과성 국소 뇌허혈 모델에서 Lamotrigine 전처치에 의한 신경세포 보호 효과

Abstract

Background : Because glutamate plays a key role in the mechanism of ischemic neuronal death, inhibition of the action of glutamate may exert a neuroprotective effect. In the present study, we tried to evaluate the neuroprotective e ffect of lamotrigine, which is known to inhibit the release of presynaptic release of glutamate by blockade of voltage sensitive sodium channel, in a rat model of transient focal cerebral ischemia. Methods : We made a transient focal ischemia(2-hour occlusion and 4-hour reperfusion) model in the Sprague-Dawley rat and lamotrigine(20mg/kg) was applied by intraperitoneal injection at 30 minutes prior to occlusion n=10). For the control group, vehicle(0.5% methyl cellulose solution, 2ml/kg) was applied in the same way(n=10). The blood glucose level of each rat was measured during operation. After reperfusion, the rats were sacrificed immediately and coronal sections of the brain were made. After staining each section with 2,3,5-triphenyltetrazolium chloride, we measured the volume of infarction. Results : The mean body weight and mean blood glucose level were not d i fferent(p>0.1). The mean volume of infarction was smaller significantly in the lamotrigine treated group than the control group(127.12¡¾3 4 .8 m m3 vs 191.07¡¾3 4 . 3 5 m m3, mean¡¾SD, p<0.001). Conclusions : These results show that lamotrigine has a neuroprotective effect in transient focal cerebral ischemia. Considering the action mechanism of lamotrigine, activation of voltage sensitive sodium channel and the following release of glutamate may play an critical role in the early ischemic neuronal death. Furthermore, it suggests the possibility of clinical use of lamotrigine as a neuroprotective agent in the acute cerebral ischemia. Korean Journal of Stroke 2000;2(1): 70~77