Nanri K, Takizawa S, Fujita H, Ogawa S, Shinohara Y
Department of Neurology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Brain Res. 1996 Nov 4;738(2):243-8. doi: 10.1016/s0006-8993(96)00777-9.
The purpose of the present study was to clarify the effect of topical administration of a nitric oxide synthase inhibitor on extracellular glutamate concentration in transient forebrain ischemia. Two microdialysis probes were inserted into the bilateral striata of Wistar rats. NG-Nitro-L-arginine (L-NNA) with or without L-arginine was topically administered into the unilateral striatum through one of the microdialysis probes, while Ringer's solution was perfused into the contralateral striatum as the control, and 14 minutes of forebrain ischemia was applied. The extracellular glutamate concentration during ischemia and subsequent reperfusion was statistically significantly higher on the 100 microM L-NNA-perfused side than on the control side, but 1 mM L-NNA was ineffective. When 100 microM L-NNA was perfused together with 500 microM L-arginine, the glutamate concentration did not differ from that on the control side. Moreover, administration of 500 microM L-arginine significantly suppressed the glutamate elevation after reperfusion. The fact that the lower dose of L-NNA increased the accumulation of glutamate during ischemia and reperfusion without altering blood flow may indicate that nitric oxide affords protection against ischemia neuronal damage. However, since the higher dose of L-NNA did not affect the glutamate concentration, it appears that the effect of nitric oxide on extracellular glutamate concentration in forebrain ischemia differs, depending on the degree of the inhibition of NOS activity.
本研究的目的是阐明一氧化氮合酶抑制剂局部给药对短暂性前脑缺血时细胞外谷氨酸浓度的影响。将两根微透析探针插入Wistar大鼠的双侧纹状体。通过其中一根微透析探针将含或不含L-精氨酸的NG-硝基-L-精氨酸（L-NNA）局部给药至单侧纹状体，同时将林格液灌注至对侧纹状体作为对照，并施加14分钟的前脑缺血。缺血及随后再灌注期间，100μM L-NNA灌注侧的细胞外谷氨酸浓度在统计学上显著高于对照侧，但1mM L-NNA无效。当100μM L-NNA与500μM L-精氨酸一起灌注时，谷氨酸浓度与对照侧无差异。此外，给予500μM L-精氨酸可显著抑制再灌注后谷氨酸的升高。较低剂量的L-NNA在不改变血流的情况下增加了缺血和再灌注期间谷氨酸的积累，这一事实可能表明一氧化氮可提供针对缺血性神经元损伤的保护作用。然而，由于较高剂量的L-NNA并未影响谷氨酸浓度，因此一氧化氮对前脑缺血时细胞外谷氨酸浓度的影响似乎因一氧化氮合酶（NOS）活性的抑制程度而异。
