Wei Yina, Ullah Ghanim, Ingram Justin, Schiff Steven J
Center for Neural Engineering, Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, Pennsylvania;
Department of Physics, University of South Florida, Tampa, Florida; Mathematical Biosciences Institute, Ohio State University, Columbus, Ohio; and.
J Neurophysiol. 2014 Jul 15;112(2):213-23. doi: 10.1152/jn.00541.2013. Epub 2014 Mar 26.
Electrophysiological recordings show intense neuronal firing during epileptic seizures leading to enhanced energy consumption. However, the relationship between oxygen metabolism and seizure patterns has not been well studied. Recent studies have developed fast and quantitative techniques to measure oxygen microdomain concentration during seizure events. In this article, we develop a biophysical model that accounts for these experimental observations. The model is an extension of the Hodgkin-Huxley formalism and includes the neuronal microenvironment dynamics of sodium, potassium, and oxygen concentrations. Our model accounts for metabolic energy consumption during and following seizure events. We can further account for the experimental observation that hypoxia can induce seizures, with seizures occurring only within a narrow range of tissue oxygen pressure. We also reproduce the interplay between excitatory and inhibitory neurons seen in experiments, accounting for the different oxygen levels observed during seizures in excitatory vs. inhibitory cell layers. Our findings offer a more comprehensive understanding of the complex interrelationship among seizures, ion dynamics, and energy metabolism.
电生理记录显示，癫痫发作期间神经元强烈放电，导致能量消耗增加。然而，氧代谢与癫痫发作模式之间的关系尚未得到充分研究。最近的研究开发了快速且定量的技术来测量癫痫发作期间的氧微区浓度。在本文中，我们建立了一个生物物理模型来解释这些实验观察结果。该模型是霍奇金 - 赫胥黎形式体系的扩展，包括钠、钾和氧浓度的神经元微环境动态。我们的模型解释了癫痫发作期间及之后的代谢能量消耗。我们还可以解释缺氧可诱发癫痫发作这一实验观察结果，即癫痫发作仅发生在组织氧压的狭窄范围内。我们还重现了实验中观察到的兴奋性和抑制性神经元之间的相互作用，解释了兴奋性与抑制性细胞层癫痫发作期间观察到的不同氧水平。我们的研究结果为癫痫发作、离子动力学和能量代谢之间复杂的相互关系提供了更全面的理解。
