Oxygen and seizure dynamics: II. Computational modeling

Abstract

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.hippocampus; hypoxia; bifurcation; epilepsy; potassium THE BRAIN CONSUMES 20% OF the body's metabolic energy with muscles and digestive system at rest, despite being only 2% of the human body mass (Attwell and Laughlin 2001). The majority of the brain's metabolic energy is dedicated to supporting neural spiking activity, most of which is used by Na ϩ -K ϩ

Role of Multiple-Scale Modeling of Epilepsy in Seizure Forecasting

“…Seizures are supported within a relatively narrow band of oxygen concentrations. A computational embodiment of the dynamical effect of oxygen demonstrated the importance of the effect of neural activity on local tissue oxygen availability, the interaction with the dependency of ion pump activity on oxygen, and the consequent emergence of instability that supports seizures (Wei et al 2014a). …”

Low-to-High Cross-Frequency Coupling in the Electrical Rhythms as Biomarker for Hyperexcitable Neuroglial Networks of the Brain

“…Moreover, astrocytes also have been shown to play a crucial role in maintaining the extracellular and -indirectly -cell volumes, both due to potassium interactions and Aquaporin 4 channels [17]. Finally, astrocytes have also been included in the models of oxygen effects on seizure dynamics [18]. Still, despite this research, the influence of these mechanisms on the seizure severity and frequency dynamics has not been conclusively established.…”

Dynamic transition of neuronal firing induced by abnormal astrocytic glutamate oscillation

“…These computational methods are also used to identify the impaired neurons underlying epilepsy404142, and in recent years some models have been developed to study the astrocyte-induced epilepsy4344454647. In the study of Nardkarni et al ., a two-compartment neuron-astrocyte model was established to account for epilepsy in these experiments, when the astrocytic neurotransmitter receptors were over-expressed4344.…”