Stability and autolysis of cortical neurons in post-mortem adult rat brains
One scientific question that weighs heavily on the feasibility of contemporary cryonics is what happens to the brain after cardiac arrest. Common wisdom has it that the brain “dies” within 5-7 minutes after circulatory arrest. This is true in the sense that patients resuscitated from such insults die of brain death (or develop higher brain death) within days of the insult. It is not true in the sense that the neuroanatomy that represents the person disappears within 5-7 minutes. Even at room temperature the post-mortem ultrastructure of the brain is quite resistant to damage for hours after cardiac arrest.
Well designed post-mortem studies into the temporal aspects of brain structure after cardiac arrest are of great importance to the science of cryonics. Such studies will not only help establish the concept of information-theoretic death as a more rigorous definition of death than clinical or biological death, but can also assist cryonics organizations in formulating objective criteria for accepting patients with (very) long ischemic times.
Unfortunately, such studies are rare and many of the studies that have been done are unreliable as a result of compounding factors such as pre-mortem brain pathology, the terminal and agonal state of the patient prior to cardiac arrest, reperfusion injury after resuscitation, and hypo- or hyperthermia after cardiac arrest. As a result, it is hard to distinguish the histological and ultrastructural changes induced by permanent global ischemia from other factors such as failed resuscitation attempts or temperature.
These limitations can be overcome in well designed animal studies of permanent complete global ischemia. One such study was conducted by Sergey V. Sheleg et al. at the Alcor Life Extension Foundation. The authors report the results of a study investigating the progressive histological and ultrastructural changes in cortical neurons following cardiac arrest at room temperature (20 degrees Celsius) in rats. Brain samples were taken at 1, 3, 6, 9, 12 and 24 hours following cardiac arrest. Temperature of the rats after cardiac arrest was measured using a deeply placed esophageal temperature probe.
The authors did not find any autolytic changes in the ultrastructure of cortical neurons in the first 6 hours after cardiac arrest. After 9 hours disappearance of ribosomes was observed in ~ 55% of the neurons. Further progression of autolysis is seen from 12-24 hours. Light microscopy did not reveal any appreciable histological changes but rouleaux formation was observed in the microcirculation of the cerebral cortex after 1 hour following cardiac arrest. The authors also found caspase-3 (an enzyme that plays a key role in apoptosis) activation in a “significant number” of neurons of the cerebellum and neocortex 9 hours following cardiac arrest.
Although the authors state that their research reflects an interest in human cardiac arrest at room temperature, it is doubtful that this model is a realistic representation of this. As can be seen in the temperature graph in the paper, the temperature of the rats drops rapidly after cardiac arrest to room temperature. Humans will take a much longer time to cool to room temperature because of their lower surface to mass ratio. As a result, the biochemical and structural changes induced by cardiac arrest may proceed at a faster pace in humans. A model that would hold the body temperature of the rats closer to their pre-mortem temperature, or follow the typical cooling curve of a post-mortem human, would be a better model to investigate such changes. The authors also do not report a control/sham group for comparison.
Although the results of this study are encouraging for the science and practice of cryonics it needs to be kept in mind that many cryonics patients do suffer prolonged terminal and agonal periods that can contribute to brain injury prior to cardiac arrest. The authors also review evidence that reintroduction of blood flow after cardiac arrest can produce more severe damage (reperfusion injury) than permanent global ischemia. Currently, data is lacking to answer the question whether more rapid cooling and better circulation of medications outweighs the risk of more ultrastructural damage as a result of (prolonged) cardiopulmonary support in cryonics patients.