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Prog Neurobiol. 2019 Dec 10:101733. doi: 10.1016/j.pneurobio.2019.101733. [Epub ahead of print]

Identifying neuronal correlates of dying and resuscitation in a model of reversible brain anoxia.

Author information

1
Institut du Cerveau et de la Moelle épinière, ICM, INSERM UMRS 1127, CNRS UMR 7225, Pitié-Salpêtrière Hospital, F-75013, Paris, France.
2
Institut du Cerveau et de la Moelle épinière, ICM, INSERM UMRS 1127, CNRS UMR 7225, Pitié-Salpêtrière Hospital, F-75013, Paris, France; Epilepsy Unit, Clinical Neurophysiology Department, AP-HP, Hôpital Pitié-Salpêtrière, F-75013, Paris, France.
3
Institut du Cerveau et de la Moelle épinière, ICM, INSERM UMRS 1127, CNRS UMR 7225, Pitié-Salpêtrière Hospital, F-75013, Paris, France; Sorbonne University, UPMC Université Paris 06, Paris, France. Electronic address: stephane.charpier@upmc.fr.

Abstract

We developed a new rodent model of reversible brain anoxia and performed continuous electrocorticographic (ECoG) and intracellular recordings of neocortical neurons to identify in real-time the cellular and network dynamics that successively emerge throughout the dying-to-recovery process. Along with a global decrease in ECoG amplitude, deprivation of oxygen supply resulted in an early surge of beta-gamma activities, accompanied by rhythmic membrane depolarizations and regular firing in pyramidal neurons. ECoG and intracellular signals were then dominated by low-frequency activities which progressively declined towards isoelectric levels. Cortical neurons during the isoelectric state underwent a massive membrane potential depolarizing shift, captured in the ECoG as a large amplitude triphasic wave known as the "wave-of-death" (WoD). This neuronal anoxic depolarization, associated with a block of action potentials and a loss of cell integrative properties, could however be reversed if brain re-oxygenation was rapidly restored (within 2-3.5 min). The subsequent slow repolarization of neocortical neurons resulted in a second identifiable ECoG wave we termed "wave-of-resuscitation" since it inaugurated the progressive regaining of pre-anoxic synaptic and firing activities. These results demonstrate that the WoD is not a biomarker of an irremediable death and unveil the cellular correlates of a novel ECoG wave that may be predictive of a successful recovery. The identification of real-time biomarkers of onset and termination of cell anoxic insult could benefit research on interventional strategies to optimize resuscitation procedures.

KEYWORDS:

Brain anoxia; Dying; Near-death experience; Neocortex; Neuronal excitability; Resuscitation

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