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

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.