星型胶质细胞参与癫痫发作的动力学机制研究

项目名称： 星型胶质细胞参与癫痫发作的动力学机制研究

项目编号： No.11472202

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 数理科学和化学

项目作者： 吴莹

作者单位： 西安交通大学

项目金额： 86万元

中文摘要： 癫痫是世界性脑神经疾病,在我国癫痫已经成为神经科第二大常见病，其发病机理尚不完全清楚，是医学界公认的一大难题。最新研究表明：神经元异常癫样放电与星形胶质细胞形状改变和功能失调有密切关系，为探索癫痫发病机理和治疗方法提供了新的思路。本项目拟从分子扩散动力学和神经动力学两个层面研究神经癫痫产生的机制。研究内容包括：1)构建胶质细胞调整突触间隙高浓度离子的动力学模型，探究胶质细胞调整细胞间隙钾离子和谷氨酸浓度调控癫痫发放的机制；2)基于胶质细胞钙离子振荡模型，以及三向突触动力学模型，研究离子通道突变、神经元间动态耦合和部分神经元非均匀耦合等条件下神经元及集群放电行为；3)构建胶质细胞调控癫痫发放的神经网络动力学模型，揭示胶质细胞参与癫痫发放的动力学机制；4)探讨细胞环境温度和电场对胶质细胞参与癫痫发放的影响。本项目为非线性动力学与神经科学交叉研究，研究结果有望为临床预防和治疗癫痫提供理论指导。

中文关键词： 癫痫；胶质细胞；非线性；神经动力学；离子振荡

英文摘要： The emergence of epilepsy is often associated with abnormality in the neuronal system, while its potential mechanism for occurrence keeps open and deserves for further investigation, as a result, many patients with epilepsy have been suffered from this kind of disease without recovery. Some evidences have confirmed that abnormal electric activities like epileptiform discharges could be greatly related to the change in cellular morphology of astrocyte and dyfunction. This project tends to detect the potential cause for neuronal epilepsy in the view of diffusive molecular dynamics and neuron dynamics, based on the nonlinear science and theory. The contents contain as follows: 1)Based on the mean field theory, a new neuron-coupled-astrocyte model is designed to the adjustment of astrocyte on ion with dense concentration in synaptic cleft, thus the potential mechanism induced by concentration fluctuation of glutamate and potassium in synaptic cleft could be found.2) Based on the model of Ca2+ oscillation coupled with gliacyte and tri-synapse, the transition of collective electric activities induced by rapid fluctuation in ion channels, time-varying coupling between neurons and heterogeneous coupling among some neurons is investigated in detail.3)Then neuron-coupled-astrocyte in networks is improved to explore the potential emergence mechanism of epilepsy by using complex network theory. 4) The effect of cell temperature and electric field radiation（eletrodiffusion process of glutamate in the cleft） are considered in the neuron-coupled-astrocyte model to detect the occurrence and development of epilepsy. The results from this project can throw light on clinical prevention and cure of epilepsy.

英文关键词： epilepsy;astrocyte;nonlinear;neuron dynamics;ion oscillation