ArticleEpilepsia2025
Electrical stimulation of stem cell-derived human neural networks for evaluating anti-seizure medications.
Article in Epilepsia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Electrical stimulation of stem cell-derived human neural networks for evaluating anti-seizure medications.Epilepsia · 2025Article
- Article
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14 authors.
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No grant is acknowledged in the PubMed record.
Abstract
objectiveCurrent preclinical epilepsy drug screening relies on animal models that poorly reflect human neurophysiology, leading to high failure rates in clinical translation. We aimed to establish a human in vitro model using human-induced pluripotent stem cell (hiPSC)-derived cortical neurons cultured on multielectrode arrays (MEAs), capable of generating precisely controlled after-discharges (ADs) through electrical stimulation. We optimized stimulation parameters to evoke epileptiform-like hypersynchronous events and validated the model using six approved antiseizure medications (ASMs).
methodshiPSCs were rapidly differentiated into NGN2 cortical neurons and co-cultured with astrocytes on a 12-electrode, 24-well MEA. Network activity was tracked weekly. Upon maturation, biphasic voltage stimuli (400-2000 mV, 10 pulses at 100 Hz, 100 μs phase width) were applied in 100 ms trains to induce ADs. Stimulation intensity was increased until a maximum spike count per burst was reached. The timing of the stimulating inter-burst interval (IBI) was shortened from 10 to 1 s. We tested six ASMs with distinct mechanisms of action for their ability to attenuate induced ADs, as measured by the area under the curve (AUC) of spikes within bursts.
resultsA ±1000 mV stimulus was sufficient to evoke robust ADs; higher voltages caused network instability without enhancing response strength. The maximum hypersynchronous bursting rate was observed with 2 s IBIs, whereas attempts to induce more frequent events using 1 s IBIs led to desynchronization and a reduction in burst frequency below baseline. Phenytoin, perampanel, clonazepam, and lamotrigine significantly reduced AUC within 5 min in a concentration-dependent manner. Vigabatrin and levetiracetam required longer pre-incubations: AUC was reduced after 6 h for levetiracetam and at 24 h for vigabatrin. SIGNIFICANCE: We present a novel hiPSC-derived, electrically induced in vitro model for screening ASM candidates. This approach captures human-relevant epileptiform dynamics, allows fine control over stimulation parameters, and enables testing of diverse drug mechanisms. Its compatibility with high-throughput platforms makes it a promising tool for ASM discovery and personalized treatment strategies.
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