Journal Article

Restoration of brain circulation and cellular functions hours post-mortem

Silbereis, John, Liu, Zhao, Skarica, Mario, Vrselja, Zvonimir, Pletikos, Mihovil, Zhuang, Zhen W., Sestan, Nenad, Waxman, Stephen G., Sinusas, Albert J., Tanaka, Brian S., Morozov, Yury M., Kaur, Navjot, Daniele, Stefano G., Latham, Stephen R., Talpo, Francesca, Alkawadri, Rafeed, Sousa, André M. M.

2019

Overview

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. A specialized technology can restore and preserve microcirculation and cellular functions hours post-mortem in an isolated pig brain.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13 / 13/106 / 13/2 / 13/21 / 13/51 / 14 / 14/19 / 14/28 / 14/63 / 59 / 59/57 / 631/378/1689/534 / 631/378/1934 / 64 / 82 / 96 / Animals / Anoxia / Apoptosis / Attenuation / Autopsy / Biochemistry / Blood flow / Brain / Brain - blood supply / Brain - cytology / Brain - metabolism / Brain - pathology / Brain architecture / Brain circulation / Brain Ischemia - metabolism / Brain Ischemia - pathology / Caspase 3 - metabolism / Cell death / Cell Survival / Cerebral Arteries - physiology / Cerebral circulation / Cerebrovascular Circulation / Cytokines / Disease Models, Animal / Edema / Electroencephalography / Energy requirements / Flow velocity / Forensic science / Hemoglobin / Hemoglobins / Homeostasis / Humanities and Social Sciences / Hypoxia, Brain - metabolism / Hypoxia, Brain - pathology / Inflammation / Inflammation - metabolism / Inflammation - pathology / Injury prevention / Investigations / Ischemia / Mammals / Medical schools / Metabolism / Microcirculation / multidisciplinary / Neurodegenerative diseases / Neuroglia - cytology / Neurons - cytology / Neurons - metabolism / Neurons - pathology / Neurophysiology / Neurosciences / Oxygen / Perfusion / Physiological aspects / Preservation / Reperfusion / Reperfusion injury / Reperfusion Injury - prevention & control / Restoration / Science / Science (multidisciplinary) / Swine / Swine - blood / Synapses - metabolism / Synapses - pathology / Technology / Time Factors / Vasodilation