Summary: A new study sheds light on the neurobiological processes that occur when we die.
A new Annals of Neurology study provides insight into the neurobiology of dying. For the study, investigators performed continuous patient monitoring following Do Not Resuscitate – Comfort Care orders in patients with devastating brain injury to investigate the mechanisms and timing of events in the brain and the circulation during the dying process.
The findings may be helpful for developing treatment strategies of cardiac arrest and stroke that may complement efforts to reestablish circulation, and also inform the debate of organ donation after cardio-circulatory death, where death is declared between two and ten minutes following the cessation of circulatory function.
“After circulatory arrest, spreading depolarization marks the loss of stored electrochemical energy in brain cells and the onset of toxic processes that eventually lead to death. Importantly, it is reversible – up to a point – when the circulation is restored,” said lead author Dr. Jens Dreier, of Universitätsmedizin Berlin, in Germany.
“There are no direct implications for patient care today. Particular challenges include the slowness of this wave that hampers its visibility in normal EEG recordings; however, this discovery may lead to improved diagnostic and treatment procedures in the future, following Max Planck’s motto that ‘insight must precede application’.”
Source: Josh Glickman – Wiley
Publisher: Organized by NeuroscienceNews.com.
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Original Research: Open access research in Annals of Neurology.
Terminal spreading depolarization and electrical silence in death of human cerebral cortex
Restoring the circulation is the primary goal in emergency treatment of cerebral ischemia. However, better understanding of how the brain responds to energy depletion could help predict the time available for resuscitation until irreversible damage and advance development of interventions that prolong this span. Experimentally, injury to central neurons begins only with anoxic depolarization. This potentially reversible, spreading wave typically starts 2 to 5 minutes after the onset of severe ischemia, marking the onset of a toxic intraneuronal change that eventually results in irreversible injury.
To investigate this in the human brain, we performed recordings with either subdural electrode strips (n = 4) or intraparenchymal electrode arrays (n = 5) in patients with devastating brain injury that resulted in activation of a Do Not Resuscitate–Comfort Care order followed by terminal extubation.
Withdrawal of life-sustaining therapies produced a decline in brain tissue partial pressure of oxygen (ptiO2) and circulatory arrest. Silencing of spontaneous electrical activity developed simultaneously across regional electrode arrays in 8 patients. This silencing, termed “nonspreading depression,” developed during the steep falling phase of ptiO2 (intraparenchymal sensor, n = 6) at 11 (interquartile range [IQR] = 7–14) mmHg. Terminal spreading depolarizations started to propagate between electrodes 3.9 (IQR = 2.6–6.3) minutes after onset of the final drop in perfusion and 13 to 266 seconds after nonspreading depression. In 1 patient, terminal spreading depolarization induced the initial electrocerebral silence in a spreading depression pattern; circulatory arrest developed thereafter.
These results provide fundamental insight into the neurobiology of dying and have important implications for survivable cerebral ischemic insults.