| Literature DB >> 30996318 |
Zvonimir Vrselja1,2, Stefano G Daniele1,2,3, John Silbereis1,2, Francesca Talpo1,2,4, Yury M Morozov1,2, André M M Sousa1,2, Brian S Tanaka5,6,7, Mario Skarica1,2, Mihovil Pletikos1,2,8, Navjot Kaur1,2, Zhen W Zhuang9, Zhao Liu9,10, Rafeed Alkawadri6,11, Albert J Sinusas9,10, Stephen R Latham12, Stephen G Waxman5,6,7, Nenad Sestan13,14,15,16,17,18,19.
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.Entities:
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Year: 2019 PMID： 30996318 PMCID： PMC6844189 DOI： 10.1038/s41586-019-1099-1
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 69.504