Epilepsy is a widespread neurological disorder marked by recurrent seizures, with about one-third of patients experiencing drug-resistant forms. While current treatments primarily target neuronal activity, emerging research highlights the critical role of astrocytes—supportive glial cells that regulate neurotransmitter levels, ion balance, metabolism, and inflammation. In epilepsy, astrocytes often become reactive, contributing to disrupted glutamate clearance, excess lactate production, water imbalance, and chronic inflammation. These dysfunctions promote neuronal hyperexcitability, synaptic remodeling, and the formation of abnormal neural circuits. Preclinical studies suggest that targeting astrocytic pathways—such as glutamate transporters, lactate dehydrogenase, and inflammatory mediators—may offer therapeutic benefits beyond symptom control, potentially modifying disease progression.
Therapies focused on astrocytes aim to restore excitatory-inhibitory balance, reestablish metabolic homeostasis, reduce neuroinflammation, and correct abnormal neural circuits. Strategies include gene therapy, pharmacologic agents, and novel noninvasive techniques like magnetic stimulation and ultrasound. Future research should prioritize better understanding astrocyte transitions, developing diagnostic imaging, and refining targeted interventions. With continued progress, astrocyte-based therapies may help overcome the limitations of current antiseizure medications and provide new hope for patients with drug-resistant epilepsy.
Reference: Chen Y, Hu J, Zhang Y, et al. Epilepsy therapy beyond neurons: Unveiling astrocytes as cellular targets. Neural Regen Res. 2026 Jan 1;21(1):23-38. doi: 10.4103/NRR.NRR-D-24-01035. Epub 2025 Jan 13. PMID: 39819836; PMCID: PMC12094549.
