ADENOSINE - A POTENTIAL MEDIATOR OF SEIZURE ARREST AND POSTICTAL REFRACTORINESS
ADENOSINE - A POTENTIAL MEDIATOR OF SEIZURE ARREST AND POSTICTAL REFRACTORINESS
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DOI：
10.1002/ana.410320504
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发表时间：
1992-11-01
影响因子：
11.2
通讯作者：
SPENCER, DD
中科院分区：
文献类型：
--
作者：
DURING, MJ;SPENCER, DD
腺苷是一种有效的抑制性神经调质，已被提议作为内源性抗惊厥药。深度电极修改，包括微透析探针植入10至16天的难治性复杂部分性癫痫的4例患者的大脑皮层，以测试的假设，在癫痫发作细胞外腺苷达到的水平，可能会抑制癫痫样活动。每例患者在单次自发性癫痫发作之前、期间和之后每隔3分钟采集双侧样本。所有癫痫发作均始于一侧海马，并传播至对侧海马。细胞外腺苷水平增加了6至31倍，增加显着更大的致癫痫海马。在癫痫发作期间，透析液中的腺苷水平达到高达2.5 μ M的浓度，反映了约65 μ M的细胞外浓度。腺苷在40至50 μ M的浓度下抑制体外癫痫样活动，因此我们报告的水平可能抑制体内癫痫发作活动。此外，腺苷水平在整个18分钟后保持高于基础值。这些数据支持腺苷在介导癫痫发作停止和发作后不应性中的作用，并表明促进腺苷的治疗可能有效地预防癫痫发作。
Adenosine is a potent inhibitory neuromodulator and has been proposed as an endogenous anticonvulsant. Depth electrodes modified to include a microdialysis probe were implanted for 10 to 16 days in the hippocampi of 4 patients with intractable complex partial epilepsy to test the hypothesis that during seizures extracellular adenosine reaches levels that may depress epileptiform activity. Samples were collected bilaterally at 3-minute intervals before, during, and after a single, spontaneous-onset seizure in each patient. All seizures commenced in one hippocampus and propagated to the contralateral hippocampus. Extracellular adenosine levels increased by 6- to 31-fold with the increase significantly greater in the epileptogenic hippocampus. During seizures, levels of adenosine in the dialysate reached concentrations as high as 2.5 muM, reflecting extracellular concentrations of approximately 65 muM. Adenosine at concentrations of 40 to 50 muM depresses epileptiform activity in vitro, so the levels we report may suppress seizure activity in vivo. Moreover, adenosine levels remain elevated above basal values for the entire 18-minute postical period. These data support the role of adenosine in mediating seizure arrest and postictal refractoriness and suggest that treatments which facilitate adenosine may be effective in preventing seizures.