Cardiac Arrest from Exsanguination of Nemestrus Macaque Monkey Causes Electrical Silencing, Terminal Spreading Depolarization and Death in Cortex
Abstract number :
1.146
Submission category :
2. Translational Research / 2E. Other
Year :
2022
Submission ID :
2204670
Source :
www.aesnet.org
Presentation date :
12/3/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:26 AM
Authors :
Tyler Sparks, MD – Medical College of Georgia-Augusta University; Jeremy Sword, PhD – Neuroscience – Medical College of Georgia-Augusta University; Dave Blake, PhD – Neuroscience – Medical College of Georgia-Augusta University; Jed Hartings, PhD – Neurosurgery – University of Cincinnati; Nulifer Yelchin, MD – Neurology – Medical College of Georgia-Augusta University; Manan Shah, MD – Neurosurgery & Neurology – Medical College of Georgia-Augusta University; Sergei Kirov, PhD – Neurosurgery – Medical College of Georgia-Augusta University; Fernando Vale, MD – Neurosurgery – Medical College of Georgia-Augusta University
Rationale: Understanding how the brain responds to terminal events can help in targeting therapies to prevent irreversible injury. While terminal events have been extensively studied in rodent models, little is known about the progression in large animal models and humans. Anoxic depolarization is a spreading wave that happens a few minutes after severe ischemia and starts a chain of events that leads to terminal injury.
Methods: To monitor injury progression in an animal model, exsanguination was performed through an arterial line in the femoral artery of a 29-year-old male nemestrinus macaque under 1% isoflurane anesthesia. Full-band electrical recordings were performed bilaterally using subdural electrode arrays situated over the central sulcus, 24 on the left hemisphere and 7 on the right, spaced 1 cm apart. An aneurysmal clip was placed over the left MCA to simulate an ischemic stroke and ECoG was recorded for 2 hours. At the end of the experiment, 60 mL of blood was withdrawn every 5 minutes until cardiac arrest at 28 minutes, when 420 mL had been withdrawn.
Results: During the two hours between MCA occlusion and cardiac arrest, spreading depolarizations and associated spreading depression of activity was recorded on the left hemisphere most lateral electrodes, starting 2 min after placing the clip. Spreading depolarizations occurred as frequently as every 10 min and propagated at a rate of 2 to 6 mm/min. No spreading depolarizations nor spreading depression of activity was recorded on the right hemisphere until cardiac arrest. On both hemispheres, activity was ultimately silenced in a step-wise manner as a result of spreading depolarization, rather than simultaneous global silencing, “non-spreading depression,” which happens a result of the rapid drop in pbtO2 from the loss of blood flow.
Conclusions: The results provide clarity into the process of brain death and electrical silencing and can be useful for treatment planning to prevent cerebral injury.
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References:
Dreier JP, Major S, Foreman B, et al. Terminal spreading depolarization and electrical silence in death of human cerebral cortex. Ann Neurol. 2018;83(2):295-310. doi:10.1002/ana.25147._x000D_
Vicente R, Rizzuto M, Sarica C, et al. Enhanced Interplay of Neuronal Coherence and Coupling in the Dying Human Brain. Front Aging Neurosci. 2022;14:813531. Published 2022 Feb 22. doi:10.3389/fnagi.2022.813531._x000D_
Borjigin J, Lee U, Liu T, et al. Surge of neurophysiological coherence and connectivity in the dying brain. Proc Natl Acad Sci U S A. 2013;110(35):14432-14437. doi:10.1073/pnas.1308285110.
Funding: NIH Grant NS083858 (SAK)
Translational Research