Background Knowledge of glutamate excitotoxicity has increased substantially over the past few decades, with multiple proposed pathways involved in inflicting damage. We sought to develop a monosodium glutamate (MSG) exposed ex vivo organotypic whole hemisphere (OWH) brain slice model of excitotoxicity to study excitotoxic processes and screen the efficacy of superoxide dismutase (SOD). Results The OWH model is a reproducible platform with high cell viability and retained cellular morphology. OWH slices exposed to MSG induced significant cytotoxicity and downregulation of neuronal excitation-related gene expression. The OWH brain slice model has enabled us to isolate and study components of excitotoxicity, distinguishing the effects of glutamate excitation, hyperosmolar stress, and inflammation. We find that extracellularly administered SOD is significantly protective in inhibiting cell death and restoring healthy mitochondrial morphology. SOD efficacy suggests that superoxide scavenging is a promising therapeutic strategy in excitotoxic injury. Conclusions Using OWH brain slice models, we can obtain a better understanding of the pathological mechanisms of excitotoxic injury, and more rapidly screen potential therapeutics.

中文翻译：

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超氧化物歧化酶可减少兴奋性毒性器官型全半球脑切片模型中谷氨酸钠诱导的损伤。

背景 在过去的几十年中，谷氨酸兴奋性毒性的知识已经大大增加，多种建议的途径涉及造成损害。我们试图开发一种暴露于体外器官型全半球 (OWH) 的兴奋性毒性脑切片模型的味精 (MSG)，以研究兴奋性毒性过程并筛选超氧化物歧化酶 (SOD) 的功效。结果 OWH 模型是具有高细胞活力和保留细胞形态的可重复平台。暴露于味精的 OWH 切片诱导显着的细胞毒性和神经元兴奋相关基因表达的下调。OWH 脑切片模型使我们能够分离和研究兴奋性毒性的成分，区分谷氨酸兴奋、高渗压力和炎症的影响。我们发现细胞外施用的 SOD 在抑制细胞死亡和恢复健康的线粒体形态方面具有显着的保护作用。SOD 功效表明超氧化物清除是一种有前途的兴奋性毒性损伤治疗策略。结论 使用OWH脑切片模型，我们可以更好地了解兴奋性毒性损伤的病理机制，更快地筛选潜在的治疗方法。