Restoration of brain circulation and cellular functions hours post-mortem

被引：181

作者：

Vrselja, Zvonimir ^{[1
,2
]}

Daniele, Stefano G. ^{[1
,2
,3
]}

Silbereis, John ^{[1
,2
]}

Talpo, Francesca ^{[1
,2
,4
]}

Morozov, Yury M. ^{[1
,2
]}

Sousa, Andre M. M. ^{[1
,2
]}

Tanaka, Brian S. ^{[5
,6
,7
]}

Skarica, Mario ^{[1
,2
]}

Pletikos, Mihovil ^{[1
,2
,8
]}

Kaur, Navjot ^{[1
,2
]}

Zhuang, Zhen W. ^{[9
]}

Liu, Zhao ^{[9
,10
]}

Alkawadri, Rafeed ^{[6
,11
]}

Sinusas, Albert J. ^{[9
,10
]}

Latham, Stephen R. ^{[12
]}

Waxman, Stephen G. ^{[5
,6
,7
]}

Sestan, Nenad ^{[1
,2
,13
,14
,15
,16
,17
]}

机构：

[1] Yale Sch Med, Dept Neurosci, New Haven, CT 06510 USA

[2] Yale Sch Med, Kavli Inst Neurosci, New Haven, CT 06510 USA

[3] Yale Sch Med, Med Scientist Training Program, New Haven, CT USA

[4] Univ Pavia, Dept Biol & Biotechnol L Spallanzani, Pavia, Italy

[5] Yale Sch Med, Ctr Neurosci & Regenerat Res, New Haven, CT USA

[6] Yale Sch Med, Dept Neurol, New Haven, CT USA

[7] VA Connecticut Healthcare Syst, Rehabil Res Ctr, West Haven, CT USA

[8] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA

[9] Yale Sch Med, Dept Internal Med, Sect Cardiovasc Med, New Haven, CT USA

[10] Yale Sch Med, Dept Radiol & Biomed Imaging, New Haven, CT USA

[11] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA

[12] Yale Univ, Interdisciplinary Ctr Bioeth, New Haven, CT USA

[13] Yale Sch Med, Dept Genet, New Haven, CT 06510 USA

[14] Yale Sch Med, Dept Psychiat, New Haven, CT 06510 USA

[15] Yale Sch Med, Dept Comparat Med, New Haven, CT 06510 USA

[16] Yale Sch Med, Yale Child Study Ctr, New Haven, CT 06510 USA

[17] Yale Sch Med, Program Cellular Neurosci Neurodegenerat & Repair, New Haven, CT 06510 USA

来源：

NATURE | 2019年 / 568卷 / 7752期

关键词：

COMPLETE ISCHEMIA; NEURONAL DEATH; MONKEY BRAIN; CARDIAC-ARREST; DOMESTIC PIG; RECOVERY; RESUSCITATION; METABOLISM; HIPPOCAMPUS; PERFUSION;

D O I：

10.1038/s41586-019-1099-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：336 / +

页数：28

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