Comparison of three administration modes for establishing a zebrafish seizure model induced by N-Methyl-D-aspartic acid
Comparison of three administration modes for establishing a zebrafish seizure model induced by N-Methyl-D-aspartic acid
复制标题
N-甲基-D-天冬氨酸诱导斑马鱼癫痫发作模型的三种给药方式的比较
DOI：
10.5498/wjp.v10.i7.150
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发表时间：
2020-07
影响因子：
3.1
通讯作者：
Xu Hong
中科院分区：
文献类型：
--
作者：
Long Xin-Yi;Wang Shuang;Luo Zhi-Wen;Zhang Xu;Xu Hong
背景癫痫是一种复杂的神经系统疾病，其特征是由脑神经元的突然异常放电引起的反复发作。它会导致短暂的大脑功能障碍，表现为异常的身体运动和意识。它可以发生在任何年龄，影响全球约6500万人，其中三分之一估计仍患有难治性癫痫发作。目前迫切需要进一步建立动物癫痫模型，这为癫痫模型的建立提供了一种方法，并可用于未来发现新的抗癫痫治疗药物。目的比较N-甲基-D-天冬氨酸（NMDA）诱发斑马鱼癫痫发作的3种给药方式。方法比较浸泡、玻璃体内注射和腹腔内注射3种途径给予NMDA对成年斑马鱼行为学的影响。我们通过观察斑马鱼的行为变化来评估神经毒性，并用癫痫发作评分对这些行为进行分级。此外，MK-801（地佐环平）和天然活性成分白藜芦醇对NMDA诱导的改变的保护作用进行了研究。结果：三种NMDA给药方法在成年斑马鱼中触发了不同的癫痫过程模式。无论给药方式如何，增加NMDA浓度后癫痫发作评分均增加。然而，浸泡曲线持续上升到一个高平台（50 min后），而玻璃体内注射和腹腔内注射的曲线在早期（10-20 min）出现尖峰，随后癫痫发作评分稳定下降。此外，白藜芦醇和MK-801预处理显著延迟癫痫发作时间并降低癫痫发作评分。结论通过比较3种给药方法，玻璃体内注射NMDA是建立斑马鱼急性癫痫模型的最佳方法。因此，在斑马鱼中的腹膜内注射可以应用于模拟疾病，例如癫痫。此外，NMDA浸泡可能是诱发持续性癫痫发作的合适方法。此外，MK-801和白藜芦醇显示出较强的抗癫痫作用，因此，它们都可能是临床上有价值的治疗癫痫的药物。
BACKGROUND Epilepsy is a complex neurological disorder characterized by recurrent, unprovoked seizures resulting from the sudden abnormal discharge of brain neurons. It leads to transient brain dysfunction, manifested by abnormal physical movements and consciousness. It can occur at any age, affecting approximately 65 million worldwide, one third of which are still estimated to suffer from refractory seizures. There is an urgent need for further establishment of seizure models in animals, which provides an approach to model epilepsy and could be used to identify novel anti-epileptic therapeutics in the future. AIM To compare three administration modes for establishing a seizure model caused by N-Methyl-D-aspartic acid (NMDA) in zebrafish. METHODS Three administration routes of NMDA, including immersion, intravitreal injection and intraperitoneal injection, were compared with regard to their effects on inducing seizure-like behaviors in adult zebrafish. We evaluated neurotoxicity by observing behavioral changes in zebrafish and graded those behaviors with a seizure score. In addition, the protective effects of MK-801 (Dizocilpine) and natural active constituent resveratrol against NMDA-induced alterations were studied. RESULTS The three NMDA-administration methods triggered different patterns of the epileptic process in adult zebrafish. Seizure scores were increased after increasing NMDA concentration regardless of the mode of administration. However, the curve of immersion continuously rose to a high plateau (after 50 min), while the curves of intravitreal injection and intraperitoneal injection showed a spike in the early stage (10-20 min) followed by a steady decrease in seizure scores. Furthermore, pretreatment with resveratrol and MK-801 significantly delayed seizure onset time and lowered seizure scores. CONCLUSION By comparing the three methods of administration, intravitreal injection of NMDA was the most suitable for establishing an acute epileptic model in zebrafish. Thus, intraperitoneal injection in zebrafish can be applied to simulate diseases such as epilepsy. In addition, NMDA immersion may be an appropriate method to induce persistent seizures. Moreover, MK-801 and resveratrol showed strong anti-epileptic effects; thus, both of them may be clinically valuable treatments for epilepsy.
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影响因子：
25
作者：
Staley, Kevin
通讯作者：
Staley, Kevin
影响因子：
3.4
作者：
Toscano CD;Kingsley PJ;Marnett LJ;Bosetti F
通讯作者：
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影响因子：
4.3
作者：
Liao, Meijiang;Kundap, Uday;Samarut, Eric
通讯作者：
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影响因子：
4.4
作者：
Yu Zhang;H. Bazzazi;R. Lima e Silva;N. Pandey;J. Green;P. Campochiaro;A. Popel
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Yu Zhang;H. Bazzazi;R. Lima e Silva;N. Pandey;J. Green;P. Campochiaro;A. Popel
影响因子：
3.4
作者：
Alfaro, Juan M.;Ripoll-Gomez, Jorge;Burgos, Javier S.
通讯作者：
Burgos, Javier S.