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Restoration of brain circulation and cellular functions hours post-mortem

Author

Listed:
  • Zvonimir Vrselja

    (Yale School of Medicine
    Yale School of Medicine)

  • Stefano G. Daniele

    (Yale School of Medicine
    Yale School of Medicine
    Yale School of Medicine)

  • John Silbereis

    (Yale School of Medicine
    Yale School of Medicine)

  • Francesca Talpo

    (Yale School of Medicine
    Yale School of Medicine
    University of Pavia)

  • Yury M. Morozov

    (Yale School of Medicine
    Yale School of Medicine)

  • André M. M. Sousa

    (Yale School of Medicine
    Yale School of Medicine)

  • Brian S. Tanaka

    (Yale School of Medicine
    Yale School of Medicine
    VA Connecticut Healthcare System)

  • Mario Skarica

    (Yale School of Medicine
    Yale School of Medicine)

  • Mihovil Pletikos

    (Yale School of Medicine
    Yale School of Medicine
    Boston University School of Medicine)

  • Navjot Kaur

    (Yale School of Medicine
    Yale School of Medicine)

  • Zhen W. Zhuang

    (Yale School of Medicine)

  • Zhao Liu

    (Yale School of Medicine
    Yale School of Medicine)

  • Rafeed Alkawadri

    (Yale School of Medicine
    University of Pittsburgh)

  • Albert J. Sinusas

    (Yale School of Medicine
    Yale School of Medicine)

  • Stephen R. Latham

    (Yale University)

  • Stephen G. Waxman

    (Yale School of Medicine
    Yale School of Medicine
    VA Connecticut Healthcare System)

  • Nenad Sestan

    (Yale School of Medicine
    Yale School of Medicine
    Yale School of Medicine
    Yale School of Medicine)

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.

Suggested Citation

  • 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 & Zha, 2019. "Restoration of brain circulation and cellular functions hours post-mortem," Nature, Nature, vol. 568(7752), pages 336-343, April.
    • Handle: RePEc:nat:nature:v:568:y:2019:i:7752:d:10.1038_s41586-019-1099-1
    DOI: 10.1038/s41586-019-1099-1
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    Cited by:

    1. Benjamin C. Creekmore & Kathryn Kixmoeller & Ben E. Black & Edward B. Lee & Yi-Wei Chang, 2024. "Ultrastructure of human brain tissue vitrified from autopsy revealed by cryo-ET with cryo-plasma FIB milling," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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