Possible alterations in GABAA receptor signaling that underlie benzodiazepine-resistant seizures.
Possible alterations in GABAA receptor signaling that underlie benzodiazepine-resistant seizures.
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作者：
Deeb TZ;Maguire J;Moss SJ
苯二氮卓类药物作为治疗癫痫持续状态（SE）的一线药物已经使用了几十年。由于尚不完全清楚的原因，苯二氮卓类药物的疗效随着癫痫发作持续时间的增加而降低。这往往迫使临床医生采取更激烈的二线和三线治疗，但并不总是成功的。苯二氮卓类药物的抗癫痫特性是由γ-氨基丁酸A型（GABAA）受体介导的。几十年的研究集中在癫痫发作后gaba能抑制失败，这可能是SE期间苯二氮卓类药物耐药的原因。然而，GABAA信号缺陷的细节在很大程度上仍然未知。因此，有必要提高我们对苯二氮卓类药物耐药机制的认识，以便制定更有效的策略。在这篇综述中，我们讨论了在人类和动物模型中支持GABAA受体功能改变作为苯二氮卓类药物耐药SE的主要潜在原因的证据。我们特别提出了基于GABAA受体数量和亚型变化以及成熟大脑中氯离子稳态紊乱的潜在影响的主流假说。
Benzodiazepines have been used for decades as the first-line treatment for status epilepticus (SE). For reasons that are not fully understood, the efficacy of benzodiazepines decreases with increasing durations of seizure activity. This often forces clinicians to resort to more drastic second- and third-line treatments that are not always successful. The antiseizure properties of benzodiazepines are mediated by γ-aminobutyric acid type A (GABAA) receptors. Decades of research have focused on the failure of GABAergic inhibition after seizure onset as the likely cause of the development benzodiazepine resistance during SE. However, the details of the deficits in GABAA signaling are still largely unknown. Therefore it is necessary to improve our understanding of the mechanisms of benzodiazepine resistance so that more effective strategies can be formulated. In this review we discuss evidence supporting the role of altered GABAA receptor function as the major underlying cause of benzodiazepine resistant SE in both humans and animal models. We specifically address the prevailing hypothesis, which is based on changes in the number and subtypes of GABAA receptors, as well as the potential influence of perturbed chloride homeostasis in the mature brain.
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影响因子：
5.3
作者：
Chamma I;Chevy Q;Poncer JC;Lévi S
通讯作者：
Lévi S
DOI：
10.1111/j.1460-9568.2009.06863.x
发表时间：
2009-08
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Bragin DE;Sanderson JL;Peterson S;Connor JA;Müller WS
通讯作者：
Müller WS
影响因子：
3.6
作者：
Avoli, Massimo;Biagini, Giuseppe;de Curtis, M
通讯作者：
de Curtis, M
影响因子：
3.4
作者：
Cohen, AS;Lin, DD;Coulter, DA
通讯作者：
Coulter, DA
影响因子：
3.3
作者：
Das, A.;Wallace, G. C.;Holmes, C.;McDowell, M. L.;Smith, J. A.;Marshall, J. D.;Bonilha, L.;Edwards, J. C.;Glazier, S. S.;Ray, S. K.;Banik, N. L.
通讯作者：
Banik, N. L.