2025 Volume 53 Issue 2 Pages 105-113
Epilepsy is a neurological disorder characterized by recurrent seizures, often driven by complex interactions between neurons and glial cells. While neuronal mechanisms of epileptogenesis have been extensively studied, growing evidence highlights the critical role of astrocytes in modulating network excitability through tripartite synapses. Astrocytes regulate extracellular ion homeostasis, neurotransmitter clearance, and synaptic plasticity, and their dysfunction contributes to seizure generation and propagation. In this review, we focus on the involvement of astrocytes in intractable epilepsy, particularly in hippocampal sclerosis (HS) and cavernous angioma (CA). Using flavoprotein fluorescence imaging and histopathological analyses, we demonstrate that astrocytic dysfunction, including impaired potassium buffering and glutamate homeostasis, plays a crucial role in hyperexcitability and seizure dynamics. Furthermore, we discuss how aberrant neural circuits, such as the subiculum-CA1 pathway in HS and the perilesional astrocytosis regions in CA, are linked to astrocyte-mediated mechanisms of epileptogenesis. These findings emphasize the importance of astrocyte-neuron interactions in seizure development and suggest that targeting astrocyte-related mechanisms could provide novel therapeutic strategies for epilepsy treatment.
