Intrasubthalamic cell transplants for epilepsy therapy: hopes and concerns
Intrasubthalamic cell transplants for epilepsy therapy: hopes and concerns
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用于癫痫治疗的底丘脑内细胞移植：希望和担忧
DOI：
10.1097/wnr.0000000000000059
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发表时间：
2013
期刊：
影响因子：
1.7
通讯作者：
M Gernert
中科院分区：
文献类型：
--
作者：
M Gernert
癫痫患者的主要治疗方法包括抗癫痫药物治疗。然而，约三分之一的患者继续癫痫发作或显示出无法忍受的不良反应，尽管适当的药物。将神经元移植到参与癫痫发作产生、传播或调节的关键脑区是治疗耐药性癫痫的一种有前途的替代实验方法。特别是对于具有多个癫痫灶或没有明确的局灶性发作的患者，对远离病灶但显著参与癫痫调制的脑结构进行治疗性操作可能是更有利的策略。通过动物实验，我们最近发现，丘脑底核（subthalamic nucleus，简称丘脑底核）可能是这方面的一个有利靶区。反复显示，GABA能传递的变化，这可以通过局部显微注射GABA升高药物或通过移植GABA释放细胞实现高度敏感。然而，在这种方法的临床转化成为现实之前，还有许多障碍需要克服和问题需要解决。这篇评论讨论了潜在的好处，以及与移植的抑制性细胞相关的问题到culture.BackgroundEpilepsies是常见的慢性神经系统疾病，其特征是反复自发性癫痫发作的中央起源。治疗的主要方法包括全身应用抗癫痫药物抑制癫痫发作的症状，通常必须在整个生命周期内持续使用。癫痫的药物治疗面临着双重挑战：首先，全身药物治疗的不良副作用很常见，其次，约三分之一的受影响患者被认为对目前可用的抗癫痫药物具有耐药性。这些耐药性患者尽管接受了适当的药物治疗，但仍继续癫痫发作。特别是定位相关的癫痫，如颞叶癫痫，其中癫痫发作源自边缘系统，其特征在于难以治疗的癫痫发作类型。对于一些耐药性患者，切除癫痫病灶可能导致癫痫发作得到控制，甚至治愈。然而，对于许多人来说，病灶切除术不是一种选择，因为难以定位病灶，对侧半球出现镜像病灶，存在多个病灶，不可接受的手术风险或预期的不良术后副作用。因此，人们对开发有前景的替代治疗方法非常感兴趣，其中将细胞移植到适当的脑靶区域是其中之一1-10。即便如此，到目前为止，癫痫的移植研究几乎完全是在动物模型中进行的，在一项初步研究中，将胎猪GABA能细胞移植到少数患有局部相关癫痫的患者的癫痫灶中，显示出令人鼓舞的抗惊厥结果11。
The mainstay of treatment of patients suffering from epilepsies involves antiepileptic drug therapy. However, about one-third of patients continue to have seizures or show intolerable adverse effects despite appropriate medication. Neuronal transplantation into key brain regions involved in seizure generation, propagation, or modulation is a promising alternative experimental approach to treat drug-resistant epilepsies. Especially for patients with multiple-epileptic foci, or without a clear focal onset, therapeutic manipulation of brain structures remote to the focus but significantly involved in seizure modulation may be a more advantageous strategy. Using animal experiments, we recently showed that the subthalamic nucleus (STN) may be an auspicious target region in this respect. The STN repeatedly showed up to be highly sensitive to changes in GABAergic transmission, which can be achieved by localized microinjection of GABA-elevating drugs or by grafting GABA-releasing cells. However, there are many hurdles to overcome and questions to resolve before clinical translation of this approach appears realistic. This commentary discusses potential benefits as well as concerns associated with grafting of inhibitory cells into the STN.BackgroundEpilepsies are common chronic neurological diseases characterized by recurrent spontaneous seizures of central origin. The mainstay of treatment involves symptomatic suppression of seizures with systemically applied antiepileptic drugs, which often has to be continued throughout live. Pharmacotherapies for epilepsies are facing a two-fold challenge: first, unwanted side effects from systemic drug treatment are common, and second, about one-third of affected patients are considered resistant to currently available antiepileptic drugs. These pharmacoresistant patients continue to have seizures despite appropriate medication. In particular the localization-related epilepsies, such as temporal lobe epilepsy, in which seizures emanate from the limbic system, are characterized by difficult-to-treat types of seizures. For some pharmacoresistant patients, resection of the seizure focus may lead to control of seizures or even a cure. For many however, focus resection is not an option because of difficulties localizing the focus, the occurrence of a mirror focus in the contralateral hemisphere, the existence of multiple foci, unacceptable surgical risks, or expected unwanted postoperative adverse effects. Thus, there is considerable interest in developing promising alternative treatment approaches, among which cell transplantation into appropriate brain target regions is one of them 1–10. Even so, grafting studies in epilepsies so far have almost exclusively been investigated in animal models, a pilot study in which fetal porcine GABAergic cells have been grafted into the seizure focus in a few patients suffering from localization-related epilepsies showed encouraging anticonvulsant results 11.
影响因子：
2.9
作者：
Banerjee S;Williamson DA;Habib N;Chataway J
通讯作者：
Chataway J
移植产生 GABA 的细胞以控制颞叶癫痫模型的癫痫发作
影响因子：
5.7
作者：
K. Thompson
通讯作者：
K. Thompson
影响因子：
3.3
作者：
Handreck, Annelie;Backofen-Wehrhahn, Bianca;Gernert, Manuela
通讯作者：
Gernert, Manuela