Superoxide dismutase reduces monosodium glutamate-induced injury in an organotypic whole hemisphere brain slice model of excitotoxicity
Superoxide dismutase reduces monosodium glutamate-induced injury in an organotypic whole hemisphere brain slice model of excitotoxicity
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DOI：
10.1186/s13036-020-0226-8
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发表时间：
2020-02-04
影响因子：
5.6
通讯作者：
Nance, Elizabeth
中科院分区：
文献类型：
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作者：
Liao, Rick;Wood, Thomas R.;Nance, Elizabeth
在过去的几十年里，谷氨酸兴奋性毒性的知识大幅增加，多个拟议的途径参与造成损害。本研究旨在建立一种谷氨酸（MSG）暴露的离体器官型全半球（OWH）脑片兴奋性毒性模型，以研究兴奋性毒性过程并筛选超氧化物歧化酶（SOD）的疗效。结果OWH模型是一个可重复的平台，具有高细胞活力和保留的细胞形态。暴露于MSG的OWH切片诱导显著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，高渗性应激和炎症的影响。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。超氧化物歧化酶的功效表明，超氧化物清除是一个有前途的治疗策略，在兴奋性毒性损伤。结论利用OWH脑片模型，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。
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.