Inhibitory effect of MS-153 on elevated brain glutamate level induced by rat middle cerebral artery occlusion.
Inhibitory effect of MS-153 on elevated brain glutamate level induced by rat middle cerebral artery occlusion.
复制标题
MS-153对大鼠大脑中动脉闭塞引起的脑谷氨酸水平升高的抑制作用。
作者：
Kazuo Umemura;Takefumi Gemba;Atsuhiro Mizuno;M. Nakashima
背景和目的
在这项研究中，我们研究了一种新的化合物，MS-153（[R]-[-]-5-甲基-1-烟酰基-2-吡唑啉），对大脑中动脉（MCA）闭塞引起的脑谷氨酸浓度升高和脑梗死体积的影响。
方法
大鼠MCA被血栓闭塞，血栓是由绿色光和光敏剂染料玫瑰红之间的光化学反应诱导的，这会导致内皮损伤，随后在光化学反应部位形成富含血小板和纤维蛋白的血栓;该方法在我们的实验室中常规用于在实验动物中产生动脉闭塞。微透析技术测定缺血边缘区细胞外谷氨酸浓度。大脑中动脉闭塞后24小时，用组织化学技术测量脑梗死的大小。从MCA闭塞后0至2小时开始，以不同剂量连续输注MS-153 24小时。
结果
在缺血边缘区，细胞外液中谷氨酸的浓度在缺血后增加了40倍。在3.13 mg/kg/h时，MS-153降低谷氨酸浓度（P <0.05）以及缺血性脑梗死的大小（P <0.05）。此外，谷氨酸摄取抑制剂DL-苏型-β-羟基天冬氨酸逆转MS-153对谷氨酸浓度的影响。
结论
MS-153导致的脑梗死面积的减小可能归因于谷氨酸释放的抑制或细胞谷氨酸摄取的增加。
BACKGROUND AND PURPOSE
In this study we investigated the effects of a novel compound, MS-153 ([R]-[-]-5-methyl-1-nicotinoyl-2-pyrazoline), on elevated brain glutamate concentrations and cerebral infarct volume induced by middle cerebral artery (MCA) occlusion in the rat.
METHODS
The rat MCA was occluded by a thrombus induced by a photochemical reaction between green light and the photosensitizer dye rose bengal, which causes endothelial injury followed by formation of a platelet- and fibrin-rich thrombus at the site of photochemical reaction; this method is routinely used in our laboratory to produce arterial occlusion in experimental animals. Extracellular glutamate concentration at the ischemic border zone was determined by a microdialysis technique. The size of cerebral infarction was measured by a histochemical technique 24 hours after MCA occlusion. MS-153 was administered at various doses as a continuous infusion for 24 hours, beginning 0 to 2 hours after MCA occlusion.
RESULTS
At the ischemic border zone, the concentration of glutamate in the extracellular fluid increased by 40-fold after ischemia. At 3.13 mg/kg per hour, MS-153 reduced glutamate concentration (P < .05) and also the size of ischemic cerebral infarction (P < .05). Furthermore, the glutamate uptake inhibitor DL-threo-beta-hydroxyaspartate reversed the effect of MS-153 on glutamate concentration.
CONCLUSIONS
The reduction in the size of cerebral infarction by MS-153 may be attributable to the inhibition of glutamate release or an increase in cellular glutamate uptake.