Nav: Home

The giant wave that marks the beginning of the end -- the neurobiology of dying

February 26, 2018

The human brain is highly sensitive to oxygen deprivation. Extensive and irreversible damage occurs within approximately 10 minutes of cardiac (and hence circulatory) arrest. For the first time, researchers from Charité - Universitätsmedizin Berlin and the University of Cincinnati have been able to study these events in humans. The results from this research, which has been published in Annals of Neurology*, may inform future treatment strategies of cardiac arrest and stroke.

Oxygen deprivation results in brain injury. For years, researchers have been studying the underlying processes in animals: within 20 to 40 seconds, the brain enters an 'energy-saving mode' - it becomes electrically inactive, and all interneuronal communication ceases. Within a few minutes, the brain's fuel reserves have become depleted that maintain the uneven distribution of ions between the inside and outside of nerve cells, and the ion gradients start to break down. This breakdown takes the form of a massive wave of electrochemical energy release in the form of heat, which is known as 'spreading depolarization'. More vividly described as a 'brain tsunami', this energy loss spreads through the cortex and other areas of the brain, triggering pathophysiological cascades which gradually poison the nerve cells. Importantly, this wave remains reversible up to a certain point in time: nerve cells will recover fully if circulation is restored before this point is reached. However, if circulation remains disrupted, the cells will die. Until now, recordings of electrical brain activity obtained from human subjects have been of limited applicability, and experts have been divided as to the transferability of results from animal-based research.

It is usually impossible to take the relevant measurements in the minutes immediately following a stroke or cardiac arrest. Under the leadership of Prof. Dr. Jens Dreier of Charité's Center for Stroke Research, and working with Prof. Jed Hartings of the Mayfield Clinic in Cincinnati, researchers have now been able to study such cases for the first time. Their research was facilitated by a very specific setup. Specialist neuromonitoring techniques, which enable the early detection and subsequent treatment of clinical complications, are becoming an increasingly common feature of modern neurocritical care. In particular, electrocorticography and invasive methods of monitoring oxygen are becoming increasingly significant. In contrast to conventional electroencephalography, electrocorticography goes beyond the process of recording epileptic seizure activity, enabling clinicians to record spreading depolarization with never-before-seen precision. Over the past few years, a number of international clinical studies have been able to confirm that, in many severe cases of acute brain injury, spreading depolarizations develop as soon as the patient's condition worsens. When this happens, treatment must target the underlying causes of this phenomenon, in order to limit its occurrence.

As part of their observational study, the researchers used state-of-the-art neuromonitoring technology. Scientific analysis of both monitoring data and each patient's clinical course showed that the event known as 'terminal spreading depolarization' also occurs in humans, beginning within minutes of circulatory arrest. "We were able to show that terminal spreading depolarization is similar in humans and animals. Unfortunately, the research community has been ignoring this essential process of central nervous system injury for decades, all because of the mistaken assumption that it does not occur in humans," explains Prof. Dreier. The reasons for this have been primarily methodological in nature. Reestablishing circulation as rapidly as possible has, until now, been the sole aim of treatment in stroke and cardiac arrest patients. "Knowledge of the processes involved in spreading depolarization is fundamental to the development of additional treatment strategies aimed at prolonging the survival of nerve cells when brain perfusion is disrupted," explains Prof. Dreier. He adds: "This of course follows from the tenet espoused by Max Planck that insight must precede application; our insights can give us hope for the future."
Dreier JP, Major S, Foreman B, Winkler MKL, Kang EJ, Milakara D, Lemale CL, DiNapoli V, Hinzman JM, Woitzik J, Andaluz N, Carlson A, Hartings JA. Terminal spreading depolarization and electric silence in death of human cortex. Ann Neurol. 2018 Jan 13. doi: 10.1002/ana.25147. PMID: 29331091.


Prof. Dr. Jens Dreier
Charité - Universitätsmedizin Berlin
Center for Stroke Research Berlin (CSB)
Charitéplatz 1, 10117 Berlin
Tel: 49-30-450-560-024


Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at