Glutamate excess and free radical formation during and following kainic acid-induced status epilepticus
Glutamate excess and free radical formation during and following kainic acid-induced status epilepticus
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红藻氨酸诱导的癫痫持续状态期间和之后谷氨酸过量和自由基形成
DOI：
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发表时间：
2002
影响因子：
2
通讯作者：
Y. Mitsuyama
中科院分区：
文献类型：
--
作者：
Y. Ueda;H. Yokoyama;A. Nakajima;J. Tokumaru;Taku Doi;Y. Mitsuyama
抽象的。海人酸（KA）诱导癫痫发作和腹侧海马CA 1区变性，但其作用机制尚不清楚。我们使用KA诱导癫痫发作在自由活动的大鼠准备在体内微透析与探针放置，然后测量细胞外谷氨酸与在线荧光检测器。通过电子顺磁共振（EPR）光谱结合自旋捕获剂α-（4-吡啶基-N-氧化物）-N-叔丁基硝酮（POBN）的灌注监测自由基的产生。通过观察从探针外源施加的3-氨基甲酰基-2，2，5，5-四甲基吡咯烷-1-氧基（氨基甲酰基-PROXYL）对氮氧自由基的清除率来测量区域抗氧化功效。在KA诱导的癫痫发作开始时观察到的细胞外谷氨酸水平增加似乎与脂质自由基的产生和残余抗氧化作用的减少有关。这些数据表明，崩溃的氧化还原状态在海马，该地区最容易受到损伤的癫痫活动，可能是至关重要的区域损伤癫痫发作。此外，我们建议，由于氧化应激导致谷氨酸转运蛋白的功能故障在高水平的细胞外谷氨酸持续全身癫痫发作与KA诱导。
Abstract. Kainic acid (KA) induces seizures and degeneration in CA1 of the ventral hippocampus, though its mechanism of action is unknown. We used KA to induce seizures in freely moving rats prepared for in vivo microdialysis with probe placement, and then measured extracellular glutamate with an online fluorometric detector. Generation of free radicals was monitored by electron paramagnetic resonance (EPR) spectroscopy coupled with perfusion of the spin-trapping agent, α-(4-pyridyl-N-oxide)-N-tert-butylnitrone (POBN). Regional antioxidant efficacy was measured by observing the eliminating ratio of nitroxide radicals, using 3-carbamoyl-2, 2, 5, 5-tetramethylpyrrolidine-1-oxyl (carbamoyl-PROXYL) applied exogenously from the probe. Increased levels of extracellular glutamate observed at the initiation of KA-induced seizures appear to be associated with generation of lipid free radicals and with a decrease in residual antioxidant effects. These data suggest that collapse of the redox state in the hippocampus, the region most vulnerable to injury from seizure activity, may be critical in the regional injury induced by seizures. Further, we propose that the functional failure of glutamate transporters due to oxidative stress results in high levels of extracellular glutamate during sustained generalized seizures induced with KA.
通过自旋捕获观察到巨噬细胞和神经细胞中一氧化氮产生的刺激和抑制。
影响因子：
7.4
作者：
Norby,SW;Weyhenmeyer,JA;Clarkson,RB
通讯作者：
Clarkson,RB