title: Generalized periodic discharges after acute cerebral ischemia: reflection of selective synaptic failure?
abstract: OBJECTIVE
  Generalized periodic discharges (GPDs) can be observed in the electroencephalogram (EEG) of patients after acute cerebral ischemia and reflect pathological neuronal synchronization. Whether GPDs represent ictal activity, which can be treated with anti-epileptic drugs, or severe ischemic damage, in which treatment is futile, is unknown. We hypothesize that GPDs result from selective ischemic damage of glutamatergic synapses, which are known to be relatively vulnerable to effects of ischemia.
  
  
  METHODS
  We employed a macroscopic model of cortical dynamics in which we increasingly eliminated glutamatergic synapses. We compared the output of the model with clinical EEG recordings in patients showing GPDs after cardiac arrest.
  
  
  RESULTS
  Selective elimination of glutamatergic synapses from pyramidal cells to inhibitory interneurons led to simulated GPDs whose waveshape and frequency matched those of patients showing GPDs after cardiac arrest. Mere reduction of glutamatergic synapses between pyramidal cells themselves did not result in GPDs.
  
  
  CONCLUSIONS
  Selective ischemic damage of glutamatergic synapses on inhibitory cortical interneurons leads to the generation of ischemia induced GPDs. Disinhibition of cortical pyramidal neurons is a candidate mechanism.
  
  
  CONCLUSIONS
  This study increases the insight in the pathophysiological mechanisms underlying the generation GPDS after acute cerebral ischemia.
authors.affiliation: Clinical Neurophysiology, MIRA-Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands; Department of Neurology and Clinical Neurophysiology, Medisch Spectrum Twente, Enschede, The Netherlands. Electronic address: M.C.Cloostermans@utwente.nl.
authors.forename: Marleen C
authors.initials: MC
authors.lastname: Tjepkema-Cloostermans
authors.affiliation: Center for Brain and Cognition, Computational Neuroscience Group, Department of Information and Communication Technologies, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Rikkert
authors.initials: R
authors.lastname: Hindriks
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
authors.affiliation: Clinical Neurophysiology, MIRA-Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands; Department of Neurology and Clinical Neurophysiology, Medisch Spectrum Twente, Enschede, The Netherlands.
authors.forename: Michel J A M
authors.initials: MJ
authors.lastname: van Putten
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000328:Adult; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D003344:Cortical Synchronization / Q000502:physiology*; D004569:Electroencephalography; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007395:Interneurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D008959:Models, Neurological; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000473:pathology / Q000502:physiology
chemical_list: D018698:Glutamic Acid
keywords: Cardiac arrest; Cerebral ischemia; Generalized periodic discharges; Meanfield model; Selective ischemic vulnerability; Synaptic failure