Human glioma cells induce hyperexcitability in cortical networks.
Human glioma cells induce hyperexcitability in cortical networks.
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DOI：
10.1111/j.1528-1167.2012.03557.x
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发表时间：
2012-08
期刊：
影响因子：
5.6
通讯作者：
Sontheimer H
中科院分区：
文献类型：
--
作者：
Campbell SL;Buckingham SC;Sontheimer H
神经胶质瘤患者经常出现癫痫发作，但与癫痫发作发展相关的因素仍然知之甚少。在这项研究中，我们评估了胶质瘤动物模型中瘤周突触网络的活性，并测试了胶质瘤异常释放的谷氨酸对胶质瘤相关癫痫网络活动的贡献。在体外，大脑切片是从移植了胶质瘤的小鼠身上制成的。利用细胞外野记录，我们分析了无镁介质在荷瘤动物和假手术对照组的切片中诱发的瘤周癫痫样活动。我们评估了柳氮磺吡啶对肿瘤相关脑片自发和诱发活动的影响，该药是XC−系统和谷氨酸释放的阻断剂。肿瘤相关的皮质网络过度兴奋。在荷瘤脑片中，无镁诱发癫痫样活动的起始潜伏期明显缩短，无镁诱发癫痫样事件的发生率较高。阻断XC-−系统的谷氨酸释放可减少诱发活动的反应面积，并完全阻断无镁诱导的发作样事件，但不能阻断发作间歇样事件。控制神经胶质瘤患者的癫痫发作是临床治疗的重要组成部分；因此，了解癫痫发作的来源至关重要。这项工作提供了肿瘤肿块扰乱瘤周突触网络活动从而导致网络兴奋性的证据。我们发现，用已获美国食品和药物管理局批准的药物SAS通过System XC−阻断谷氨酸释放，可以抑制无镁诱导的癫痫样事件，类似于其他用于降低癫痫活性的化学物质。因此，我们建议进一步的研究应将SAS视为一种有前景的药物，以帮助治疗与胶质瘤相关的癫痫发作。
Patients with gliomas frequently present with seizures, but the factors associated with seizure development are still poorly understood. In this study, we assessed peritumoral synaptic network activity in a glioma animal model and tested the contribution of aberrant glutamate release from gliomas on glioma-associated epileptic network activity. In vitro brain slices were made from glioma-implanted mice. Using extracellular field recordings, we analyzed peritumoral epileptiform activity induced by Mg2+-free medium in slices from tumor-bearing animals and sham-operated controls. We assessed the effect of sulfasalazine (SAS), a blocker of system xc− and glutamate release, on spontaneous and evoked activity in tumor-associated slices. Tumor-associated cortical networks were hyperexcitable. The onset latency of Mg2+-free-induced epileptiform activity was significantly shorter in tumor-bearing slices, and the incidence of Mg2+-free-induced ictal-like events was higher. Block of glutamate release from system xc− decreased the response area of evoked activity and completely blocked Mg2+-free-induced ictal-like, but not interictal-like events. Control of seizures in patients with gliomas is an essential component of clinical management; therefore, understanding the origin of seizures is vital. This work provides evidence that peritumoral synaptic network activity is disrupted by tumor masses resulting in network excitability. We show that blocking glutamate release via system xc− with SAS, a drug already approved by the US Food and Drug Administration (FDA), can inhibit Mg2+-free-induced ictal-like epileptiform events similar to other chemicals used to decrease seizure activity. We therefore suggest that further studies should consider SAS a promising agent to aid in the treatment of seizures associated with gliomas.
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影响因子：
5.6
作者：
Feng, ZY;Durand, DM
通讯作者：
Durand, DM
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