面向癫痫的神经元微环境动力学建模方法

Neuronal Microenvironment Dynamics Modeling Methods for Epilepsy

癫痫是由大脑神经元超同步异常放电所引起的一种常见的慢性神经系统疾病。大量生理实验和神经计算建模研究表明,神经元异常放电是癫痫发作的电生理基础,而神经元微环境动力学改变是引起神经元结构和功能发生变化,进而刺激神经元异常放电,导致癫痫发作产生和发展的潜在原因。基于此,本文首先从影响神经元微环境改变的四个主要因素(离子浓度、能量代谢、神经递质和细胞体积)出发,分别就其动力学建模的神经机制和建模方法两方面进行系统阐述与分析,然后对未来可探索的研究方向进行展望,以期更加全面地了解该领域的发展动态和研究进展,为进一步研究癫痫异常放电模式的动力学本质以及癫痫发病的神经机制奠定良好的理论基础。

Epilepsy is a common chronic neurological disorder caused by hypersynchronous abnormal discharges of neurons in the brain.Extensive physiological experiments and neural computational modeling studies have found that abnormal neuronal discharges are the electrophysiological basis of epileptic seizures.In addition,alterations in neuronal microenvironment dynamics are potential causes of neuronal structural and functional changes that stimulate abnormal neuronal discharges,which in turn lead to the generation and development of epileptic seizures.Based on this point,this review paper first systematically elaborates and analyzes the four main factors influencing the alteration of neuronal microenvironment,including ion concentration,energy metabolism,neurotransmitters and cell volume,in terms of the neural mechanisms and modeling methods of their dynamics modeling.The main methods and processes of microenvironmental dynamics modeling for epilepsy are employing mathematical and biophysical expressions to model the dynamics of neuronal microenvironment alterations associated with epileptic seizures found in physiological experiments,and then analyzing and exploring the dynamic nature of neuronal epileptic discharges generation and transition through numerical simulations and bifurcation analysis.Among the epileptic discharge patterns mainly include epileptic seizure/bursting(SZ),spreading depolarizations(SD),hypoxic spreading depolarization(HSD),tonic firing(TF),and depolarization block(DB),etc.Existing works have revealed and verified that disruption of neuronal microenvironment homeostasis caused by loss of ionic homeostasis(e.g.,excessive accumulation of intracellular Na+and Cl−as well as extracellular K+),imbalance of excitatory and inhibitory neurotransmitters(e.g.,excessively high concentration of Glu and low concentration of GABA in the extracellular space or synaptic clefts),depletion of energy metabolism substances(e.g.,insufficient supply of O2 and ATP or excessive energy consumption due to abnormal neuronal discharges),cytotoxic swelling,etc.,which can induce the generation and development of seizures.In combination with related works on the neuronal microenvironment dynamics modeling methods,we finally discuss and summarize the future research directions.It is expected to give a comprehensive perspective on the development trends and research progress in this field,and provide the favorable theoretical foundation for further research on the dynamic nature of epileptic discharge patterns and the neural mechanisms of epilepsy.