Restoration of brain circulation and cellular functions hours post-mortem.
Animals
Autopsy
Brain
/ blood supply
Brain Ischemia
/ metabolism
Caspase 3
/ metabolism
Cell Survival
Cerebral Arteries
/ physiology
Cerebrovascular Circulation
Disease Models, Animal
Hypoxia, Brain
/ metabolism
Inflammation
/ metabolism
Microcirculation
Neuroglia
/ cytology
Neurons
/ cytology
Perfusion
Reperfusion Injury
/ prevention & control
Swine
/ blood
Synapses
/ metabolism
Time Factors
Vasodilation
Journal
Nature
ISSN: 1476-4687
Titre abrégé: Nature
Pays: England
ID NLM: 0410462
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
22
02
2018
accepted:
01
03
2019
entrez:
19
4
2019
pubmed:
19
4
2019
medline:
27
11
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30996318
doi: 10.1038/s41586-019-1099-1
pii: 10.1038/s41586-019-1099-1
pmc: PMC6844189
mid: NIHMS1048971
doi:
Substances chimiques
Caspase 3
EC 3.4.22.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
336-343Subventions
Organisme : NIH HHS
ID : S10 OD021845
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007205
Pays : United States
Organisme : NIMH NIH HHS
ID : RF1 MH117064
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH113257
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
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