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Circadian-Like Rhythmicity of Extracellular Brain Glutamate in Epilepsy.
Frontiers in Neurology ( IF 3.4 ) Pub Date : 2020-05-15 , DOI: 10.3389/fneur.2020.00398
Mani Ratnesh S Sandhu 1 , Roni Dhaher 2 , Shaun E Gruenbaum 3 , Raaisa Raaisa 4 , Dennis D Spencer 2 , Milena K Pavlova 5 , Hitten P Zaveri 6 , Tore Eid 1
Affiliation  

Seizures often exhibit striking circadian-like (~24-h) rhythms. While chronotherapy has shown promise in treating epilepsy, it is not widely used, in part because the patterns of seizure rhythmicity vary considerably among patients and types of epilepsy. A better understanding of the mechanisms underlying rhythmicity in epilepsy could be expected to result in more effective approaches which can be tailored to each individual patient. The excitatory neurotransmitter glutamate is an essential modulator of circadian rhythms, and changes in the extracellular levels of glutamate likely affect the threshold to seizures. We used a reverse translational rodent model of mesial temporal lobe epilepsy (MTLE) combined with long-term intracerebral microdialysis to monitor the hourly concentrations of glutamate in the seizure onset area (epileptogenic hippocampus) over several days. We observed significant 24-h oscillations of extracellular glutamate in the epileptogenic hippocampus (n = 4, JTK_CYCLE test, p < 0.05), but not in the hippocampus of control animals (n = 4). To our knowledge, circadian glutamate oscillations have not been observed in a seizure onset region, and we speculate that the oscillations contribute to the rhythmicity of seizures in MTLE.

中文翻译:

癫痫中细胞外谷氨酸的昼夜节律性。

癫痫发作通常表现出惊人的昼夜节律(〜24小时)节律。尽管计时疗法已显示出治疗癫痫的希望,但并未得到广泛使用,部分原因是患者和癫痫类型的发作性节律性模式差异很大。对癫痫节律的潜在机制有更深入的了解,有望产生出更有效的方法,可针对每个患者量身定制。兴奋性神经递质谷氨酸是昼夜节律的重要调节剂,细胞外谷氨酸水平的变化可能影响癫痫发作的阈值。我们使用了中颞叶癫痫(MTLE)的反向翻译啮齿动物模型与长期脑内微透析相结合,以监测几天内癫痫发作区(癫痫发作海马体)的谷氨酸每小时浓度。我们在致癫痫的海马体中观察到细胞外谷氨酸的显着24小时振荡(n = 4,JTK_CYCLE测试,p <0.05),但在对照动物的海马体中则未见(n = 4)。据我们所知,尚未在癫痫发作区域观察到昼夜节律性谷氨酸振荡,我们推测这种振荡有助于MTLE癫痫发作的节律性。但不在对照动物的海马中(n = 4)。据我们所知,尚未在癫痫发作区域观察到昼夜节律性谷氨酸振荡,我们推测这种振荡有助于MTLE癫痫发作的节律性。但不在对照动物的海马中(n = 4)。据我们所知,尚未在癫痫发作区域观察到昼夜节律性谷氨酸振荡,我们推测这种振荡有助于MTLE癫痫发作的节律性。
更新日期:2020-05-15
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