Liver protects neuron viability and electrocortical activity in post-cardiac arrest brain injury
Brain injury is the leading cause of mortality among patients who survive cardiac arrest (CA). Clinical studies have shown that the presence of post-CA hypoxic hepatitis or pre-CA liver disease is associated with increased mortality and inferior neurological recovery. In our in vivo global cerebral ischemia model, we observed a larger infarct area, elevated tissue injury scores, and increased intravascular CD45+ cell adhesion in reperfused brains with simultaneous hepatic ischemia than in those without it. In the ex vivo brain normothermic machine perfusion (NMP) model, we demonstrated that addition of a functioning liver to the brain NMP circuit significantly reduced post-CA brain injury, increased neuronal viability, and improved electrocortical activity. Furthermore, significant alterations were observed in both the transcriptome and metabolome in the presence or absence of hepatic ischemia. Our study highlights the crucial role of the liver in the pathogenesis of post-CA brain injury.
Authors
- Liqiang Zhan
- Rongxing Xie
- Yuexin Li (ORCID: https://orcid.org/0000-0001-8525-2853)
- Chengjun Sun (ORCID: https://orcid.org/0000-0003-3333-6080)
- Meixian Yin (ORCID: https://orcid.org/0000-0001-8525-7603)
- Björn Nashan (ORCID: https://orcid.org/0000-0001-7587-9935)
- Andrea Schlegel (ORCID: https://orcid.org/0000-0002-9385-9847)
- Qiang Zhao (ORCID: https://orcid.org/0000-0002-6369-1393)
- Zehua Jia (ORCID: https://orcid.org/0000-0002-6640-8485)
- Ningxin Gao
- Linhe Wang (ORCID: https://orcid.org/0000-0001-7365-5209)
- Guixing Xu (ORCID: https://orcid.org/0000-0002-8040-3656)
- Tielong Wang (ORCID: https://orcid.org/0000-0001-7547-9819)
- Shanzhou� Huang (ORCID: https://orcid.org/0000-0002-7575-5841)
- Di Liu (ORCID: https://orcid.org/0000-0001-8251-7182)
- Zhiheng Zhang (ORCID: https://orcid.org/0000-0003-4299-5379)
- Zhiyong Guo (ORCID: https://orcid.org/0000-0002-5458-6268)
- Xiaoshun He (ORCID: https://orcid.org/0000-0001-5317-9612)
- Yixi Zhang (ORCID: https://orcid.org/0000-0002-6820-8196)
- Donghua Zheng
- Yifan Zhu (ORCID: https://orcid.org/0000-0001-5202-0626)
- Shujiao He (ORCID: https://orcid.org/0000-0003-3128-2541)
- Jin Xu
- Caihui Zhu
Institutions
- University of Science and Technology of China (CN)
- Sun Yat-sen University (CN)
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- China International Science and Technology Cooperation (CN)
- Key Laboratory of Guangdong Province (CN)
- The First Affiliated Hospital, Sun Yat-sen University (CN)
- Guangdong Academy of Medical Sciences (CN)
- Guangdong Provincial People's Hospital (CN)
- Southern Medical University (CN)
Publication Details
- Journal
- EMBO Molecular Medicine
- Published
- 2024-09-19
- DOI
- https://doi.org/10.1038/s44321-024-00140-z
- Citations
- 5
- Primary Topic
- Cardiac Arrest and Resuscitation
- Type
- article
- Field-Weighted Citation Impact
- 3.45
Funders
- National Natural Science Foundation of China
- Guangdong Medical Research Foundation
- Science and Technology Planning Project of Guangdong Province