Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 You Yi Road, Chongqing 400016, China.
Med Hypotheses. 2011 Jun;76(6):871-6. doi: 10.1016/j.mehy.2011.02.039. Epub 2011 Mar 22.
Drug refractory is an important clinical problem in epilepsy, affecting a substantial number of patients globally. Mechanisms underlying drug refractory need to be understood to develop rational therapies. Current two prevailing theories on drug refractory epilepsy (DRE) include the target hypothesis and the transporter hypothesis. However, those hypotheses could not be adequate to explain the mechanisms of all the DRE. Thus, we propose another possible mechanism of DRE, which is neural network hypothesis. It is hypothesized that seizure-induced alterations of brain plasticity including axonal sprouting, synaptic reorganization, neurogenesis and gliosis could contribute to the formation of abnormal neural network, which has not only avoided the inhibitory effect of endogenous antiepileptic system but also prevented the traditional antiepileptic drugs from entering their targets, eventually leading to DRE. We will illustrate this hypothesis at molecular and structural level based on our recent studies and other related researches.
耐药性是癫痫的一个重要临床问题，影响着全球大量的患者。为了开发合理的治疗方法，需要了解耐药性背后的机制。目前，关于耐药性癫痫（DRE）有两种流行的理论，包括靶点假说和转运体假说。然而，这些假说不能充分解释所有 DRE 的机制。因此，我们提出了 DRE 的另一种可能机制，即神经网络假说。该假说认为，癫痫引起的脑可塑性改变，包括轴突发芽、突触重组、神经发生和神经胶质增生，可能导致异常神经网络的形成，这不仅避开了内源性抗癫痫系统的抑制作用，还阻止了传统抗癫痫药物进入其靶点，最终导致 DRE。我们将根据我们最近的研究和其他相关研究，从分子和结构水平上说明这一假说。
