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Nature. 2019 Apr;568(7752):336-343. doi: 10.1038/s41586-019-1099-1. Epub 2019 Apr 17.

Restoration of brain circulation and cellular functions hours post-mortem.

Vrselja Z1,2, Daniele SG1,2,3, Silbereis J1,2, Talpo F1,2,4, Morozov YM1,2, Sousa AMM1,2, Tanaka BS5,6,7, Skarica M1,2, Pletikos M1,2,8, Kaur N1,2, Zhuang ZW9, Liu Z9,10, Alkawadri R6,11, Sinusas AJ9,10, Latham SR12, Waxman SG5,6,7, Sestan N13,14,15,16,17,18,19.

Author information

1
Department of Neuroscience, Yale School of Medicine, New Haven, CT, USA.
2
Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT, USA.
3
Medical Scientist Training Program (MD-PhD), Yale School of Medicine, New Haven, CT, USA.
4
Department of Biology and Biotechnology L. Spallanzani, University of Pavia, Pavia, Italy.
5
Center for Neuroscience and Regeneration Research, Yale School of Medicine, New Haven, CT, USA.
6
Department of Neurology, Yale School of Medicine, New Haven, CT, USA.
7
Rehabilitation Research Center, VA Connecticut Healthcare System, West Haven, CT, USA.
8
Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA, USA.
9
Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
10
Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA.
11
Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
12
Interdisciplinary Center for Bioethics, Yale University, New Haven, CT, USA.
13
Department of Neuroscience, Yale School of Medicine, New Haven, CT, USA. nenad.sestan@yale.edu.
14
Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT, USA. nenad.sestan@yale.edu.
15
Department of Genetics, Yale School of Medicine, New Haven, CT, USA. nenad.sestan@yale.edu.
16
Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA. nenad.sestan@yale.edu.
17
Department of Comparative Medicine, New Haven, CT, USA. nenad.sestan@yale.edu.
18
Yale Child Study Center, Yale School of Medicine, New Haven, CT, USA. nenad.sestan@yale.edu.
19
Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale School of Medicine, New Haven, CT, USA. nenad.sestan@yale.edu.

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.

PMID:
30996318
DOI:
10.1038/s41586-019-1099-1

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