......of the Four Hours.

Nature, Published:
17 April 2019
Restoration of brain circulation and cellular functions hours post-mortem
Full paper, https://go.nature.com/2KPntVe
The brains of humans and other mammals are highly vulnerable to interruptions in blood flow and decreases in oxygen levels. Here we describe the restoration and maintenance of microcirculation and molecular and cellular functions of the intact pig brain under ex vivo normothermic conditions up to four hours post-mortem. We have developed an extracorporeal pulsatile-perfusion system and a haemoglobin-based, acellular, non-coagulative, echogenic, and cytoprotective perfusate that promotes recovery from anoxia, reduces reperfusion injury, prevents oedema, and metabolically supports the energy requirements of the brain. With this system, we observed 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. 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.
it is important to distinguish between resuscitation of neurophysiological activity and recovery of integrated brain functions (that is, neurological recovery). We have found encouraging evidence that brings into question the time-course and cessation of molecular and cellular brain functions following prolonged circulatory arrest. Future studies and considerations will spur further development and implementation of this technology to study broad scientific questions in the large, mammalian brain.

Angiogram, video