Protective effects of ghrelin on brain mitochondria after cardiac arrest and resuscitation
Abstract
Mitochondrial dysfunction plays a critical role in brain injury after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Our recent study demonstrated that ghrelin protected against post-resuscitation brain injury with an elevated expression of mitochondrial uncoupling protein 2 (UCP2). However, the effects of ghrelin on mitochondrial dysfunction after CA are not clear. In the present study, the protective role of ghrelin was evaluated on mitochondrial dysfunction and the subsequent damage induced by CA in rats. In addition, mitochondrial unfolded protein response (UPRmt), an intrinsic cytoprotective pathway, was observed at the same time. Either vehicle (saline) or ghrelin (80 μg/kg) was injected blindly immediately after 6 min of CA and successful resuscitation. Neurological deficit was evaluated 6 h after CA and then cortex was collected for assessments. As a result, we found that ghrelin significantly improved the neurological deficit score in rats after CA. The functional analysis of isolated mitochondria revealed that ghrelin improved the mitochondrial ATP synthesis capacity and significantly reduced the reactive oxygen species (ROS) leakage after 6 h of CA. Concomitantly, we observed an increased ATP level and an attenuated oxidative stress in ghrelin treated animals. Moreover, ghrelin markedly improved the mitochondrial morphology compared with the vehicle animals. Further research revealed that ghrelin treatment significantly activated the UPRmt as demonstr…
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Ghrelin could affect microglia functions indirectly by modulating other brain cell types that do express GHSR, such as neurons and astrocytes.
“Hence, ghrelin could affect microglia functions indirectly by modulating other brain cell types that do express the GHSR, such as neurons [53, 54, 57] and astrocytes [58].”
From Protective PLCG2 variants associate with a delayed onset of Alzheimer’s disease among heterozygous APOE ε4 carriers (2026) · cites this paper as [57]
Cites
The neurological effects of ghrelin in brain diseases: Beyond metabolic functions
Jiao, Q., Du, X., Li, Y., Gong, B., Shi, L., Tang, T., & Jiang, H. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.12.010 · Cited by 62 · see citing works
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Acylated Ghrelin as a Multi-Targeted Therapy for Alzheimer's and Parkinson's Disease
Reich, N., & Hölscher, C. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.614828 · Cited by 48 · see citing works
Liu, Y.-F., Zhang, L., Zhang, S.-M., Liu, J., Li, X.-H., Yang, K., Yang, D., Liu, Y., Sun, L., Liu, F.-Y., et al. (2023) · Molecular Medicine · doi:10.1186/s10020-023-00651-4 · Cited by 39 · see citing works
Research progress of ghrelin on cardiovascular disease
Yuan, M.-J., Li, W., & Zhong, P. (2021) · Bioscience Reports · doi:10.1042/bsr20203387 · Cited by 32
The role of ghrelin/GHS-R1A signaling in nonalcohol drug addictions
Sustkova-Fiserova, M., Charalambous, C., Khryakova, A., Certilina, A., Lapka, M., & Šlamberová, R. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23020761 · Cited by 12 · see citing works
Duan, W.-N., Sun, Q., Wu, X.-J., Xia, Z., Warner, D., Ulloa, L., Yang, W., & Sheng, H. (2022) · Neuromodulation (Malden, Mass.) · doi:10.1016/j.neurom.2021.12.014 · Cited by 10
Gong, X.-J., Fan, X.-H., Yin, X.-X., Xu, T.-H., Li, J., Guo, J.-L., Zhao, X.-K., Wei, S.-J., Yuan, Q.-H., Wang, J.-L., et al. (2022) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2022.11302 · Cited by 7 · see citing works
Ghrelin Alleviates Endoplasmic Reticulum Stress in MC3T3E1 Cells by Inhibiting AMPK Phosphorylation
Lv, X., Zhang, Q., Cheng, B.-F., Xin, Y., Wang, J., Li, J.-J., Li, C., & Yang, N.-L. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/9940355 · Cited by 3 · see citing works
“Previous studies have shown that there is no significant difference between the ghrelin alone treatment group and the control group [22, 23].”
ResultJeskanen, H., Heikkinen, S., Kervinen, I., Lehtisalo, J., Ngandu, T., Willman, R.-M., Rosa, J., Hoffmann, D., FinnGen, Leinonen, V., et al. (2026) · Alzheimer's Research & Therapy · doi:10.1186/s13195-026-01957-1 · Cited by 1 · see citing works
“Hence, ghrelin could affect microglia functions indirectly by modulating other brain cell types that do express the GHSR, such as neurons [53, 54, 57] and astrocytes [58].”
The protective PLCG2 variants delay Alzheimer's disease onset age in APOE ϵ4 carriersPreprint
Jeskanen, H., Heikkinen, S., Kervinen, I., Lehtisalo, J., Ngandu, T., Willman, R.-M., Rosa, J., Hoffmann, D., FinnGen, Leinonen, V., et al. (2025) · medRxiv · doi:10.1101/2025.09.22.25336304
“Hence, ghrelin could affect microglia functions indirectly by modulating other brain cell types that do express the GHSR, such as neurons (52,53,56) and astrocytes (57).”
- Authors
- Xu, H., Li, Y., Liu, R., Wu, L., Zhang, C., Ding, N., Ma, A., Zhang, J., & Xie, X.
- Affiliations
- Affiliated Hospital of Jining Medical University (CN)
- Fudan University (CN)
- Corresponding author
- Xie, Xuemeng
- Venue
- Neuropeptides
- Publisher
- Elsevier BV
- Published
- 2019-08
- Volume
- 76
- Pages
- 101936
- ISSN
- 0143-4179 (ISSN-L)
- OpenAlex
- W2944893444
- Cited by
- 12
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 2 · 2022: 4 · 2021: 2 · 2020: 1
- FWCI
- 2.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropeptides (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Doctoral Scientific Research Foundation of Affiliated Hospital of Jining Medical University (2016-BS-013)
- National Natural Science Foundation of China (81272063, 81601658)
- Topics
- Health Sciences › Medicine › Emergency Medicine › Cardiac Arrest and Resuscitation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Keywords
- ghrelin, cardiac arrest, cardiopulmonary resuscitation, post-resuscitation brain injury, mitochondrial dysfunction, mitochondrial unfolded protein response, ATP production, reactive oxygen species, oxidative stress, mitochondrial morphology, heat shock proteins, neuroprotection
- MeSH terms
- Adenosine Triphosphate, Animals, Brain, Heart Arrest, Male, Mitochondria, Cardiopulmonary Resuscitation, Rats, Sprague-Dawley, Oxidative Stress, Neuroprotective Agents, Ghrelin, Unfolded Protein Response
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