A recent article published in Nature (volume 568, pages336–343 (2019) appears to have a great impact on the current criteria of death that could even affect protocols of organ donation (read our article Organ donation for transplantation in children with cardiac arrest).

To test their hypothesis, the authors developed an extracorporeal pulsatile-perfusion system, which they call BrainEx (BEx). Using this system, they achieved “preservation of cytoarchitecture; attenuation of cell death; and restoration of vascular dilatory and glial inflammatory responses, spontaneous synaptic activity, and active cerebral metabolism in the absence of global electrocorticographic activity”. As a result, they concluded that “these findings demonstrate that under appropriate conditions the isolated, intact large mammalian brain possesses an underappreciated capacity for restoration of microcirculation and molecular and cellular activity after a prolonged post-mortem interval”.

Blood flow studies support current criteria

The study shows the basis of the current criteria: “Many mammalian species have large, energy-demanding brains that are highly susceptible to anoxia and cessation of blood flow. Studies in both humans and experimental animals have shown that oxygen stores, global electrical activity, and consciousness are lost within seconds of interrupted blood flow, while glucose and ATP stores are depleted within minutes. The convergence of these factors has been widely proposed to initiate a progressive, and largely irreversible, a cascade of apoptosis, necrosis, and axonal damage.”

They affirm that current criteria of neural cell death within minutes is questionable


“However, several observations have questioned the inevitability of neural cell death minutes, or even hours, after cessation of brain perfusion.

  • First, tissue specimens with sufficient viability for cell and organotypic slice cultures, as well as for electrophysiological recordings have been taken from human and other mammalian brains hours after death.
  • Second, mitochondria remain functional for up to 10 hours post-mortem in human cerebral cortical tissue.
  • Third, in cats and macaques, 1 hour of complete global ischaemia can be followed by neuronal, electrophysiological, and metabolic recovery after reperfusion.
  • Last, full neurological recovery from prolonged asystole has been reported in humans with hypothermic, and recent clinical findings have suggested that thrombectomies performed up to 16 h after an ischaemic insult can result in favourable patient outcomes.

The discovery of the  brain’s capacity of restoration change current death paradigma

These data suggest that the initiation and duration of cell death after anoxia or ischaemia may span a longer temporal interval than is appreciated, allowing for a multifaceted intervention that could stop the progression of damaging cellular programs initiated by the insult.

Therefore, the authors postulate that, under appropriate conditions, certain molecular and cellular functions in the large mammalian brain may retain at least partial capacity for restoration after a prolonged post-mortem interval.” said the authors.

 

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