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首页> 外文期刊>The European Journal of Neuroscience >Riluzole is a potent drug to protect neonatal rat hypoglossal motoneurons in vitro from excitotoxicity due to glutamate uptake block.
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Riluzole is a potent drug to protect neonatal rat hypoglossal motoneurons in vitro from excitotoxicity due to glutamate uptake block.

机译：利鲁唑是一种有效的药物，可在体外保护新生大鼠舌下运动神经元免受谷氨酸摄取阻滞引起的兴奋性毒性。

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Excitotoxic damage to motoneurons is thought to be an important contribution to the pathogenesis of amyotrophic lateral sclerosis (ALS), a slowly developing degeneration of motoneurons that, in most cases of sporadic occurrence, is associated with impaired glial glutamate uptake. Riluzole is the only drug licensed for symptomatic ALS treatment and is proposed to delay disease progression. As riluzole is administered only after full ALS manifestation, it is unclear if its early use might actually prevent motoneuron damage. We explored this issue by using, as a simple in vitro model, hypoglossal motoneurons (a primary target of ALS) of the neonatal rat brainstem slice preparation exposed to excitotoxic stress due to glutamate uptake block by DL-threo-beta-benzyloxyaspartate (TBOA). TBOA evoked sustained network bursting, early (1 h) enhancement of the S100B immunostaining of gray matter astrocytes, and activated the motoneuronal stress ATF-3 transcription factor; 4 h later, loss (30%) of motoneuron staining ensued and pyknosis appeared. Riluzole (5 muM; applied 15 min after TBOA) inhibited bursting, decreased the frequency of spontaneous glutamatergic events, reversed changes in S100B immunostaining and prevented late loss of motoneuron staining. These results show that excitotoxicity induced by glutamate uptake block developed slowly, and was sensed by glia and motoneurons with delayed cell death. Our data provide novel evidence for the neuroprotective action of riluzole on motoneurons and glia when applied early after an excitotoxic stimulus.
机译：运动神经元的兴奋性毒性损害被认为是肌萎缩性侧索硬化症（ALS）发病机理的重要贡献，肌萎缩性侧索硬化症是一种缓慢发展的运动神经元变性，在大多数情况下是偶然发生的，与胶质谷氨酸的摄取受损有关。利鲁唑是唯一被许可用于症状性ALS治疗的药物，并被提议延缓疾病进展。由于利鲁唑仅在完全ALS表现后才给药，因此尚不清楚其早期使用是否可能真正预防运动神经元损伤。我们通过使用新生大鼠脑干切片制剂的舌下运动神经元（ALS的主要靶点）作为一个简单的体外模型，探讨了该问题，它由于谷氨酸摄取被DL-苏-β-β-苄氧基天冬氨酸（TBOA）阻断而暴露于兴奋毒性。 TBOA引起持续的网络爆发，增强灰质星形胶质细胞S100B免疫染色的早期（1小时），并激活了动脑神经应激ATF-3转录因子。 4小时后，运动神经元染色消失（30％），并出现固缩。利鲁唑（5μM; TBOA后15分钟应用）可抑制突发，降低自发性谷氨酸能事件的发生频率，逆转S100B免疫染色的变化并防止运动神经元染色的后期丢失。这些结果表明，谷氨酸摄取阻滞诱导的兴奋性毒性发展缓慢，并被胶质细胞和运动神经元所感知，并延迟了细胞死亡。我们的数据提供了利鲁唑在兴奋性毒性刺激后早期应用时对运动神经元和神经胶质细胞的神经保护作用的新证据。

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