HiPSC-Derived Neuronal Networks on Micro-Electrode Arrays: a Functional Model of the Ischemic Penumbra

Acute ischemic stroke, caused by cerebral blood flow blockage, leads to neuronal damage driven by a complex pathophysiological cascade of processes, among which excessive glutamate release plays an important role. In this study, we developed a human-derived in vitro model mimicking the loss of oxygen and excessive glutamate, evaluating the effect on neuronal network activity, cell viability, and synaptic puncta. We found that hypoxia combined with glutamate significantly reduced network activity, with the most severe suppression observed at 500 μΜ glutamate. After 48 hours, the number of synaptic puncta decreased in the group treated with glutamate, indicating synaptic loss. These findings may prove to be a valuable model for studying ischemic stroke and potential neuroprotective therapies as it simplifies and captures some key aspects of the cellular response to hypoxia in combination with glutamate.Clinical Relevance- This study introduces a novel human-derived in vitro model to advance the understanding of ischemic stroke, serving as a promising platform for testing potential therapeutic strategies and facilitating the transition from preclinical research to clinical applications.