Effects of Non-invasive, Targeted, Neuronal Lesions on Seizures in a Mouse Model of Temporal Lobe Epilepsy.
Effects of Non-invasive, Targeted, Neuronal Lesions on Seizures in a Mouse Model of Temporal Lobe Epilepsy.
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DOI：
10.1016/j.ultrasmedbio.2020.01.008
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发表时间：
2020-05
影响因子：
2.9
通讯作者：
Wintermark M
中科院分区：
文献类型：
--
作者：
Zhang Y;Zhou H;Qu H;Liao C;Jiang H;Huang S;Ghobadi SN;Telichko A;Li N;Habte FG;Doyle T;Woznak JP;Bertram EH;Lee KS;Wintermark M
手术治疗耐药性癫痫可以是相当有效的，但仍然大大利用不足。进行了一项初步研究，以测试使用非侵入性、非消融性方法产生局灶性神经元损失来治疗颞叶癫痫啮齿动物模型中的癫痫发作的可行性。在这项研究中，自发的，复发性癫痫发作建立在匹鲁卡品诱导的癫痫持续状态（SE）的小鼠模型。SE后稳定后，监测基线行为癫痫发作30天。然后通过使用MRI引导的低强度聚焦超声（MRgFUS）产生靶向海马的血脑屏障（BBB）的非侵入性打开，通过该低强度聚焦超声，腹膜内施用的神经毒素（喹啉酸）获得进入脑实质以产生局灶性神经元损失。然后在该程序后监测行为癫痫发作30天，随后制备脑用于神经元损失部位的组织学分析。所有动物（n=11）的行为性癫痫发作的平均频率降低了21.2%。沿着海马体纵轴的组织学分析显示，大多数动物（n=8）表现出主要位于海马体中间方面的神经元损失，而间隔方面保留。另外两只中间海马体受损的动物也表现出海马体间隔方面明显的双侧损伤。最后一只动物的神经元损失总体上可忽略不计。值得注意的是，神经元损失的网站沿着纵向轴的海马影响癫痫发作的结果。没有双侧隔海马损伤的动物癫痫发作频率平均降低27.7%，而双侧隔海马损伤的动物癫痫发作频率实际上增加了18.7%。没有神经元损失的动物表现出癫痫发作频率增加19.6%。结果表明，给药动物的癫痫发作频率总体降低。而且，沿着海马体纵轴沿着的神经元损失部位似乎在减少癫痫发作活动中起关键作用。这些试点数据是有希望的，他们鼓励更多的和更全面的研究，检查有针对性的，非侵入性的，神经元病变治疗癫痫的影响。
Surgery to treat drug-resistant epilepsy can be quite effective but remains substantially underutilized. A pilot study was undertaken to test the feasibility of using a non-invasive, non-ablative, approach for producing focal neuronal loss to treat seizures in a rodent model of temporal lobe epilepsy. In this study, spontaneous, recurrent seizures were established in a mouse model of pilocarpine-induced status epilepticus (SE). After post-SE stabilization, baseline behavioral seizures were monitored for 30 days. Non-invasive opening of the Blood-Brain Barrier (BBB) targeting the hippocampus was then produced by using MRI-guided, low-intensity Focused Ultrasound (MRgFUS), through which a neurotoxin (Quinolinic Acid) administered intraperitoneally gained access to the brain parenchyma to produce focal neuronal loss. Behavioral seizures were then monitored for 30 days after this procedure, and brains were subsequently prepared for histological analysis of the sites of neuronal loss. The average frequency of behavioral seizures in all animals (n=11) was reduced by 21.2%. Histological analyses along the longitudinal axis of the hippocampus showed that most of the animals (n=8) exhibited neuronal loss located primarily in the intermediate aspect of the hippocampus, while sparing the septal aspect. Two other animals with damage to the intermediate hippocampus also exhibited prominent bilateral damage to the septal aspect of the hippocampus. A final animal had negligible neuronal loss overall. Notably, the site of neuronal loss along the longitudinal axis of the hippocampus influenced seizure outcomes. Animals that did not have bilateral damage to the septal hippocampus displayed a mean decrease in seizure frequency of 27.7%, while those with bilateral damage to septal hippocampus actually increased seizure frequency by 18.7%. The animal without neuronal loss exhibited an increase in seizure frequency of 19.6%. The findings indicate an overall decrease in seizure frequency in treated animals. And, the site of neuronal loss along the longitudinal axis of the hippocampus appears to play a key role in reducing seizure activity. These pilot data are promising, and they encourage additional and more comprehensive studies examining the effects of targeted, non-invasive, neuronal lesions for the treatment of epilepsy.
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影响因子：
16.2
作者：
Fanselow, Michael S.;Dong, Hong-Wei
通讯作者：
Dong, Hong-Wei
影响因子：
9.9
作者：
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2.2
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2.9
作者：
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影响因子：
3.3
作者：
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