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Session: Poster Session 1 (Even numbers)
Session starts: Thursday 26 January, 16:00
Presentation starts: 16:00

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Eva Voogd (University of Twente)
Sara Pires Monteiro (University of Twente)
Jeannette Hofmeijer (University of Twente)
Monica Frega (University of Twente)

Abstract:
Cerebral ischemia is a pathological condition caused by lack of blood flow to the brain, where low oxygen and glucose levels have detrimental effects on neuronal functioning and viability. So far, effects of neuroprotective therapies derived from animal models could not be translated to patients. A human disease model holds potential to improve identification and translation of new treatment strategies. Here, we created a human-induced pluripotent stem cell (hiPSC) derived neuronal model to investigate key pathomechanisms in cerebral ischemia and identify potential treatment strategies. In this model, we can assess neuronal activity with micro-electrode arrays and synaptic connections, as well as cell survival, with immunocytochemical techniques. We showed that hiPSC-derived neuronal networks have decreased spontaneous activity and decreased synchronous activity during and after hypoxia, indicating decreased network connectivity. In line with these findings, our results showed decreased synaptic connections and, subsequently, decreased cell survival during hypoxia. We used optogenetics to generate hiPSC-derived neurons responsive to light to investigate whether neuronal network stimulation would be neuroprotective during and after hypoxia. Our results showed that baseline levels of spontaneous and synchronous neuronal network activity were maintained with optogenetic stimulation during and after hypoxia. In addition, we investigated effects of hypothermia. The results showed preservation of synapses during hypoxia in hiPSC-derived neurons subjected to hypothermia. We conclude that hiPSC-derived neuronal networks are vulnerable to hypoxia, with synaptic failure being a key pathomechanism. We also conclude that neuronal network stimulation as well as hypothermia hold potential to prevent loss of network functioning during and after hypoxia.