Liver protects neuron viability and electrocortical activity in post-cardiac arrest brain injury

Zhiyong Guo ^1,2,3, Meixian Yin ^4,5,6,7, Chengjun Sun ^4,5,6,8

¹Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, China. guozhiy2@mail.sysu.edu.cn.
²Guangdong Provincial Key Laboratory of Organ Medicine, Guangzhou, China. guozhiy2@mail.sysu.edu.cn.
³NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, China. guozhiy2@mail.sysu.edu.cn.
⁴Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, China.
⁵Guangdong Provincial Key Laboratory of Organ Medicine, Guangzhou, China.
⁶NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, China.
⁷Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
⁸Department of Organ Transplantation, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
⁹Department of Neurosurgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
¹⁰Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
¹¹Organ Transplant Center, The First Affiliated Hospital of the University of Science and Technology of China, Hefei, China.
¹²General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
¹³State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, China.
¹⁴Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, China. zhaoq37@mail.sysu.edu.cn.
¹⁵Guangdong Provincial Key Laboratory of Organ Medicine, Guangzhou, China. zhaoq37@mail.sysu.edu.cn.
¹⁶Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, China. hexsh@mail.sysu.edu.cn.
¹⁷Guangdong Provincial Key Laboratory of Organ Medicine, Guangzhou, China. hexsh@mail.sysu.edu.cn.

⁰Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, China. guozhiy2@mail.sysu.edu.cn.

Embo Molecular Medicine +

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September 19, 2024

View abstract on PubMed

Summary

The liver plays a critical role in brain injury after cardiac arrest (CA). Protecting liver function can improve neurological recovery and reduce mortality in CA survivors.

Area Of Science

Neuroscience
Hepatology
Critical Care Medicine

Background

Brain injury is the primary cause of death for cardiac arrest (CA) survivors.
Post-CA hypoxic hepatitis or pre-existing liver disease correlates with worse outcomes and neurological recovery.

Purpose Of The Study

To investigate the liver's role in the pathogenesis of post-CA brain injury.
To evaluate the impact of hepatic ischemia on cerebral injury.
To assess the neuroprotective potential of a functioning liver in a post-CA setting.

Main Methods

Utilized an in vivo global cerebral ischemia model to assess brain injury with and without hepatic ischemia.
Employed an ex vivo brain normothermic machine perfusion (NMP) model to study the liver's effect on brain injury.
Analyzed transcriptome and metabolome alterations in the presence and absence of hepatic ischemia.

Main Results

Simultaneous hepatic ischemia exacerbated brain injury, increasing infarct size and tissue damage in vivo.
The presence of a functioning liver in the brain NMP circuit significantly reduced post-CA brain injury.
Neuronal viability and electrocortical activity improved with hepatic support in the NMP model.
Significant transcriptomic and metabolomic changes were observed related to hepatic ischemia.

Conclusions

The liver is a crucial factor in the development of brain injury following cardiac arrest.
Preserving liver function may be a therapeutic target for improving neurological outcomes after CA.
Further research into the liver-brain axis in post-CA conditions is warranted.

Keywords:

Brain Injury Cardiac Arrest Ketone Body Production Liver Dysfunction Normothermic Machine Perfusion

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