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.This beautiful work shows that the brain has a much greater capacity for restoration that had been realized. The authors were able to obtain intracellular recordings from hippocampus pyramidal cells. However:
Monitoring of electrical activity from the dorsal surface of the brain using clinical-grade surface grid electrodes and electrocorticography (ECoG; also known as intracranial electroencephalography, EEG) revealed that spontaneous global activity did not reemerge and that ECoG activity was isoelectric throughout BEx perfusion. This indicates that the organization and/or summation of synaptic activity of individual neurons was inadequate to elicit detectable network activity as assessed by ECoG.
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