Many COVID-19 patients treated for weeks or months on mechanical ventilation were slow to regain consciousness even after sedation was removed. A new article on Proceedings of the National Academy of Sciences offers the hypothesis that this strange response could be the result of a state of dormancy that the brain invokes to protect cells from injury when oxygen is scarce. A very similar kind of condition, characterized by the same characteristic change in brain rhythms, is seen not only in cardiac arrest patients treated by cooling their body temperature, a method called “hypothermia,” but also by the painted turtle, which has evolved a form of self-repression to cope with long periods of oxygen deprivation, or ‘anoxia’, when it hibernates underwater. “We suggest that hypoxia combined with certain therapeutic maneuvers may lead to an as yet unrecognized protective down-regulation state (PDS) in humans that leads to prolonged recovery of consciousness in patients with severe COVID-19 after cessation of mechanical ventilation and in postcardiac arrest patients treated with hypothermia,” authors Nicholas D. Schiff and Emery N. Brown wrote. “In severe patients with COVID-19 we hypothesize that the specific combination of intermittent hypoxia, severe metabolic stress, and GABA-mediated depression may trigger PDS.” Schiff is the Jerold B. Katz Professor of Neurology and Neuroscience at the Feil Family Brain Research Institute at Weill Cornell Medicine. Brown is the Edward Hood Taplin Professor of Medical Engineering and Computational Neuroscience at The Picower Institute for Learning and Memory and the Institute for Medical Engineering and Science at MIT. He is also an anesthesiologist at Massachusetts General Hospital and the Warren M. Zapol Professor of Anesthesiology at Harvard Medical School. A motivating observation for the pair’s hypothesis is that cardiac arrest patients treated with hypothermia, COVID-19 patients with prolonged awakenings after sedation and ventilation, and the hibernating painted turtle display a brain rhythm pattern called “burst suppression”. In the same journal a decade ago, ShiNung Ching, Brown and colleagues described a model suggesting that burst suppression is a pattern of activity that signals the brain to reduce energy use when there are insufficient reserves. In this way, the brain limits the damage that neurons might otherwise suffer trying to function at full capacity. “Biophysical modeling has shown that burst suppression is likely a signature of a neurometabolic state that maintains basic cellular function in states of reduced energy availability,” the authors wrote. Turtles appear to achieve this state by rapidly increasing the release of GABA, a neurotransmitter chemical known to reduce nerve activity in the brain, hours after oxygen becomes scarce. This release of GABA, known as “endogenous anesthesia for the anoxic turtle brain” reduces the energy demand of brain cells. The authors see a direct parallel in COVID patients who are frequently given sedatives whose effects are mediated by GABA. Speed up recovery If Brown and Schiff’s hypotheses are correct, they write, then there may be a key two-part approach to better resuscitate COVID patients from unconsciousness after weaning. The first part is the administration of Szeto-Schiller peptides (small protein fragments) known to improve neuronal production of the energy metabolism molecule ATP. This could restore the ability of brain cells to produce energy when they return to a more active state. The second part requires a pair of drugs that will restore neural activity and communication by boosting the neurotransmitters glutamate and acetylcholine, essentially neutralizing GABA in reducing neural activity and metabolism. “Our analysis predicts the existence of a human form of PDS that may underlie prolonged recovery of consciousness after treatment for severe COVID-19 or treatment for postcardiac arrest treated with hypothermia,” Brown and Schiff wrote. “The possible existence of human PDS suggests many testable hypotheses for further investigation and the possibility of developing new therapeutic strategies.” More information: Schiff, Nicholas D., Down-regulated protective states in the human brain: A potential lesson from COVID-19, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2120221119. doi.org/10.1073/pnas.2120221119 Provided by the Massachusetts Institute of Technology Reference: Are COVID ‘comas’ indicative of a protective hibernation state? (2022, November 7) retrieved November 7, 2022 by This document is subject to copyright. Except for any fair dealing for purposes of private study or research, no part may be reproduced without written permission. Content is provided for informational purposes only.
