title: Progression of Neuronal Damage in an In Vitro Model of the Ischemic Penumbra.
abstract: Improvement of neuronal recovery in the ischemic penumbra around a brain infarct has a large potential to advance clinical recovery of patients with acute ischemic stroke. However, pathophysiological mechanisms leading to either recovery or secondary damage in the penumbra are not completely understood. We studied neuronal dynamics in a model system of the penumbra consisting of networks of cultured cortical neurons exposed to controlled levels and durations of hypoxia. Short periods of hypoxia (pO2≈20mmHg) reduced spontaneous activity, due to impeded synaptic function. After ≈6 hours, activity and connectivity partially recovered, even during continuing hypoxia. If the oxygen supply was restored within 12 hours, changes in network connectivity were completely reversible. For longer periods of hypoxia (12-30 h), activity levels initially increased, but eventually decreased and connectivity changes became partially irreversible. After ≈30 hours, all functional connections disappeared and no activity remained. Since this complete silence seemed unrelated to hypoxic depths, but always followed an extended period of low activity, we speculate that irreversible damage (at least partly) results from insufficient neuronal activation. This opens avenues for therapies to improve recovery by neuronal activation.
authors.affiliation: Clinical Neurophysiology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: le Feber
authors.affiliation: Clinical Neurophysiology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.
authors.forename: Stelina
authors.initials: S
authors.lastname: Tzafi Pavlidou
authors.affiliation: Clinical Neurophysiology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.
authors.forename: Niels
authors.initials: N
authors.lastname: Erkamp
authors.affiliation: Clinical Neurophysiology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.|Department of Clinical Neurophysiology, Medisch Spectrum Twente, Enschede, The Netherlands.
authors.forename: Michel J A M
authors.initials: MJ
authors.lastname: van Putten
authors.affiliation: Clinical Neurophysiology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.|Department of Neurology, Rijnstate Hospital, Arnhem, The Netherlands.
authors.forename: Jeannette
authors.initials: J
authors.lastname: Hofmeijer
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000831:Animals, Newborn; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology; D015687:Cell Hypoxia; D063132:Connectome; D004558:Electric Stimulation; D008839:Microelectrodes; D008959:Models, Neurological; D009415:Nerve Net / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010100:Oxygen / Q000494:pharmacology*; D061251:Primary Cell Culture; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D010100:Oxygen