Restoration of brain circulation and cellular functions hours post-mortem

Zvonimir Vrselja, Stefano G. Daniele, John Silbereis, Francesca Talpo, Yury M. Morozov, André M. M. Sousa, Brian S. Tanaka, Mario Skarica, Mihovil Pletikos, Navjot Kaur, Zhen W. Zhuang, Zhao Liu, Rafeed Alkawadri, Albert J. Sinusas, Stephen R. Latham, Stephen G. Waxman and Nenad Sestan ()
Additional contact information
Zvonimir Vrselja: Yale School of Medicine
Stefano G. Daniele: Yale School of Medicine
John Silbereis: Yale School of Medicine
Francesca Talpo: Yale School of Medicine
Yury M. Morozov: Yale School of Medicine
André M. M. Sousa: Yale School of Medicine
Brian S. Tanaka: Yale School of Medicine
Mario Skarica: Yale School of Medicine
Mihovil Pletikos: Yale School of Medicine
Navjot Kaur: Yale School of Medicine
Zhen W. Zhuang: Yale School of Medicine
Zhao Liu: Yale School of Medicine
Rafeed Alkawadri: Yale School of Medicine
Albert J. Sinusas: Yale School of Medicine
Stephen R. Latham: Yale University
Stephen G. Waxman: Yale School of Medicine
Nenad Sestan: Yale School of Medicine

Nature, 2019, vol. 568, issue 7752, 336-343

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41586-019-1099-1

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