Effect of long-term spontaneous recurrent seizures or reinduction of status epilepticus on the development of supragranular mossy fiber sprouting
Effect of long-term spontaneous recurrent seizures or reinduction of status epilepticus on the development of supragranular mossy fiber sprouting
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DOI：
10.1016/s0920-1211(99)00054-6
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发表时间：
1999-09-01
影响因子：
2.2
通讯作者：
Mello, LEAM
中科院分区：
文献类型：
--
作者：
Longo, BM;Mello, LEAM
在最近的一份报告中，我们表明，蛋白质合成抑制剂放线菌酮 (CHX) 能够阻止苔藓纤维萌芽 (MFS)，否则会由毛果芸香碱 (Pilo) 诱导的癫痫持续状态 (SE) 触发，并且还可以相对保护海马神经元死亡。在这种情况下，动物仍然表现出自发性复发性癫痫发作（SRS），这使我们质疑发芽的苔藓纤维在产生这些癫痫发作中所起的作用。在癫痫患者和动物模型中，SE（如果存在）和/或 SRS 对 MFS 发展的相对贡献尚不清楚。在本研究中，我们研究了 MFS、SE 和 SRS 之间的关系，并评估了 CHX 诱导的 MFS 阻断本质上是暂时的还是永久性的。我们进行了一项长期研究，其中包括在 CHX 存在的情况下接受 Pilo 诱导的 SE 并在 8 至 10 个月后处死的动物，以及在 CHX 存在的情况下接受 Pilo 诱导的 SE 的动物，并在第一次诱导后 45 天用 Pilo 重新诱导 SE，但这一次是在没有 CHX 的情况下进行的。即使在 CHX 存在下触发第一次（或唯一一次）SE 事件的动物中，重新诱导 SE 或长期慢性癫痫发作也能够触发颗粒上 MFS。 MFS 与 SRS 的频率没有任何关联，因此似乎更关键地依赖于时间。我们目前的研究结果表明，在毛果芸香碱模型中，MFS 既不是 SRS 的原因，也不是 SRS 的结果。 (C) 1999 Elsevier Science B.V. 保留所有权利。
In a recent report we have shown that a protein synthesis inhibitor, cycloheximide (CHX), is able to block the mossy fiber sprouting (MFS) that would otherwise be triggered by pilocarpine (Pilo)-induced status epilepticus (SE), and also gives relative protection against hippocampal neuronal death. Under this condition animals still showed spontaneous recurrent seizures (SRS) which led us to question the role played by sprouted mossy fibers in generating those seizures. In both patients and animal models of epilepsy the relative contribution of SE (when present) and/or SRS for the development of MFS is not known. In the present study we investigated the relationship between MFS, SE and SRS, and evaluated whether the CHX-induced blockade of MFS was transient or permanent in nature. We performed a chronic study which included animals subject to Pilo-induced SE in the presence of CHX and sacrificed between 8 and 10 months later, and animals that were subject to Pilo-induced SE in the presence of CHX and underwent a reinduction of SE with Pilo, 45 days after the first induction, but this time in the absence of CHX. Re-induction of SE or a long period of chronic seizures, were able to trigger supragranular MFS even in animals where the first (or only) SE event was triggered in the presence of CHX. MFS did not show any association with the frequency of SRS, and thus seemed to depend more critically on time. Our current findings allow us to suggest that MFS are neither the cause nor the consequence of SRS in the pilocarpine model. (C) 1999 Elsevier Science B.V. All rights reserved.