Enhanced release of synaptic glutamate underlies the potentiation of oxygen-glucose deprivation-induced neuronal injury after induction of NOS-2.
Enhanced release of synaptic glutamate underlies the potentiation of oxygen-glucose deprivation-induced neuronal injury after induction of NOS-2.
复制标题
突触谷氨酸释放的增强是 NOS-2 诱导后氧-葡萄糖剥夺诱导的神经元损伤增强的基础。
DOI：
10.1016/j.expneurol.2004.06.018
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发表时间：
2004
影响因子：
5.3
通讯作者：
Hewett,SandraJ
中科院分区：
文献类型：
--
作者：
Vidwans,AniruddhaS;Hewett,SandraJ
Reactive nitrogen oxide species (RNOS) may contribute to the progression/enhancement of ischemic injury by augmentation of glutamate release, reduction of glutamate uptake, or a combination of both. Consistent with this, induction of nitric oxide synthase (NOS-2) in murine neocortical cell cultures potentiated neuronal cell death caused by combined oxygen–glucose deprivation in association with a net increase in extracellular glutamate accumulation. However, uptake of glutamate via high affinity, sodium-dependent glutamate transporters was unimpaired by induction of NOS-2 under either aerobic or anaerobic conditions. Further, blocking possible routes of extra-synaptic glutamate release with NPPB [5-nitro-2-(3-phenylpropylamino)-benzoic acid], a volume-sensitive organic anion channel blocker, or TBOA (d,l-threo-β-benzyloxyaspartate), an inhibitor of glutamate transport, exacerbated rather than ameliorated injury. Finally, treatment with riluzole or tetanus toxin attenuated the enhancement in both glutamate accumulation and oxygen–glucose deprivation-induced neuronal injury supporting the idea that increased synaptic release of glutamate underlies, at least in part, the potentiation of neuronal injury by RNOS after NOS-2 induction.
