Dynamic analysis of epileptic seizures caused by energy failure after ischemic stroke

Abstract

Energy is essential for neuronal electrical activity. An inadequate energy supply affects ion homeostasis and even induces epileptic seizures. Ischemic stroke is an important cause of energy failure and further leads to seizures. However, few computational models have focused on the impact of energy failure caused by ischemic stroke on epileptic seizures. To investigate the mechanism, we established a detailed biophysical model consisting of a neuron, an astrocyte, a capillary, and the extracellular space. First, we studied the effect of energy failure caused by ischemic stroke on neuronal discharge. The results demonstrate that ischemic stroke could cause spontaneous seizures and stimulate seizures of neurons, and prove that the cause of epileptic seizures is the destruction of the ion concentration gradient caused by energy failure. More importantly, we investigated the impact of energy failure on energy metabolism and found that compared with the normal discharge, the main energy that neurons depend on in epileptic seizures after ischemic stroke changes from lactate to glucose, and the astrocyte-neuron lactate shuttle (ANLS) is of great significance. Finally, we investigated the mechanism of inhibiting epileptic seizures, and the results revealed that inhibiting the LDH process in astrocytes and enhancing the ability of astrocytes to ingest extracellular glutamate are beneficial for inhibiting neuronal seizures. Most of the results are consistent with the experimental conclusion, and the results also reveal that astrocytes have neuroprotective effects and are a good target for inhibiting epileptic seizures.