Fluorocitrate‐mediated astroglial dysfunction causes seizures
Fluorocitrate‐mediated astroglial dysfunction causes seizures
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DOI：
10.1002/jnr.10743
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发表时间：
2003-10
影响因子：
4.2
通讯作者：
J. Willoughby;L. Mackenzie;M. Broberg;A. Thorén;A. Medvedev;N. Sims;M. Nilsson
中科院分区：
文献类型：
--
作者：
J. Willoughby;L. Mackenzie;M. Broberg;A. Thorén;A. Medvedev;N. Sims;M. Nilsson
星形胶质细胞在癫痫发生中的作用已经被假设，但还没有确定。低剂量的氟柠檬酸通过阻断乌头酸酶，特异性和可逆地干扰星形胶质细胞的代谢，乌头酸酶是三羧酸循环中不可或缺的一种酶。我们使用大脑皮层注射氟柠檬酸，剂量表明可以选择性地抑制星形胶质细胞代谢，以确定星形胶质细胞紊乱是否会导致癫痫发作。氟烷麻醉大鼠，大脑皮层注射0.8nmoL氟柠檬酸钠。植入硬膜外脑电(EEG)电极，停止麻醉，观察动物。在所有实验中，15只接受氟柠檬酸治疗的动物中有14只表现出癫痫样脑电放电，一些动物表现出惊厥发作。最早在注射氟柠檬酸后30分钟就开始排出。注射辛醇，而不是吸入氟烷，以测试缝隙连接在脑电放电产生中的可能参与，阻断或推迟了氟柠檬酸盐后放电的发生。这些结果表明，局灶性大脑皮质星形胶质细胞功能障碍导致局灶性癫痫样放电，有时导致惊厥发作，这一过程可能依赖于缝隙连接介导的效应。©2003 Wiley-Liss公司
A role for astroglia in epileptogenesis has been hypothesised but is not established. Low doses of fluorocitrate specifically and reversibly disrupt astroglial metabolism by blocking aconitase, an enzyme integral to the tricarboxylic acid cycle. We used cerebral cortex injections of fluorocitrate, at a dose that we demonstrated to inhibit astroglial metabolism selectively, to determine whether astroglial disturbances lead to seizures. Rats were halothane‐anesthetized, and 0.8 nmol of sodium fluorocitrate was injected into the cerebral cortex. Extradural electroencephalogram (EEG) electrodes were implanted, after which the anesthesia was ceased and the animals were observed. In all experiments, 14 of 15 fluorocitrate‐treated animals exhibited epileptiform EEG discharges, with some animals exhibiting convulsive seizures. Discharges commenced as early as 30 min postfluorocitrate injection. Intraperitoneal octanol, but not halothane by inhalation, given to test the possible participation of gap junctions in EEG discharge generation, blocked or delayed the occurrence of discharges after fluorocitrate. These results indicate that focal cerebrocortical astroglial dysfunction leads to focal epileptiform discharges and sometimes to convulsive seizures and that the process possibly depends on effects mediated by gap junctions. © 2003 Wiley‐Liss, Inc.