PMID- 36463944 OWN - NLM STAT- MEDLINE DCOM- 20221219 LR - 20221222 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 938 DP - 2023 Jan 5 TI - Ginsenoside-Rg1 mitigates cardiac arrest-induced cognitive damage by modulating neuroinflammation and hippocampal plasticity. PG - 175431 LID - S0014-2999(22)00692-6 [pii] LID - 10.1016/j.ejphar.2022.175431 [doi] AB - Ginsenoside-Rg1 can effectively ameliorate mental disorders, but whether ginsenoside-Rg1 plays a neuroprotective role in cardiac arrest and cardiopulmonary resuscitation (CA/CPR)-induced cognitive impairment remains unclear. In this study, a 5-min asphyxia-based CA/CPR rat model was established to explore the mechanisms underlying the effects of ginsenoside-Rg1 (40 mg.kg-1.d-1, ip, 14 days) on its cognitive alterations. These CA/CPR rats displayed spatial learning and memory impairment in the Morris water maze, as reflected in the compromised basal synaptic transmission and long-term potentiation (LTP) at the Schaffer collateral of hippocampal CA1 area in vivo electrophysiology, whereas the ginsenoside-Rg1 remarkably mitigated these alterations. Next, we found that ginsenoside-Rg1 inhibited hippocampal neuroinflammation by alleviating the CA/CPR-induced hippocampal activation of microglia and astrocytes and the overexpression of related proinflammatory cytokines interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha). In addition, ginsenoside-Rg1 improved CA/CPR-induced hippocampal neuronal apoptosis, dendritic spines and synaptic ultrastructure defects as associated with the upregulation of the key synaptic regulatory proteins. Furthermore, ginsenoside-Rg1 could ameliorate CA/CPR-induced aberrant expression of the key regulators of hippocampal glutamate signaling pathways, excitatory amino acid transporter 2 (EAAT2), excitatory amino acid transporter 1 (EAAT1), Glutamine Synthetase (GS), GluN2B, and glutamate. In conclusion, ginsenoside-Rg1 exerts its neuroprotective effects by ameliorating hippocampus-dependent neuroglia activation-mediated neuroinflammation and neuroplasticity deficits, shedding new light on the therapeutic intervention of CA/CPR-related cognitive disorders. CI - Copyright (c) 2022. Published by Elsevier B.V. FAU - Wu, Zhangbi AU - Wu Z AD - Department of Emergency Medicine, the First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China. FAU - Huang, Jialin AU - Huang J AD - Department of Emergency Medicine, the First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China. FAU - Bai, Xiaojie AU - Bai X AD - Department of Emergency Medicine, the First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China. FAU - Wang, Qunan AU - Wang Q AD - School of Public Health, Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes/Anhui Provincial Key Laboratory of Population Health and Aristogenics, Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Hefei, 230032, China. FAU - Wang, Fen AU - Wang F AD - Department of Geriatric Endocrinology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China. FAU - Xu, Jun AU - Xu J AD - Department of Emergency Medicine, the First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China. FAU - Tang, Huiping AU - Tang H AD - Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, 230027, China; Auditory Research Laboratory, School of Life Sciences, University of Science and Technology of China, Hefei, 230027, China. FAU - Yin, Chunying AU - Yin C AD - Cryo-EM Center, University of Science and Technology of China, Hefei, 230027, China. FAU - Wang, Yu AU - Wang Y AD - Department of Emergency Medicine, the First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China. FAU - Yu, Feng AU - Yu F AD - Department of Emergency Medicine, the First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China. Electronic address: 3351416872@qq.com. FAU - Zhang, Hong AU - Zhang H AD - Department of Emergency Medicine, the First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China. Electronic address: zhanghong20070703@163.com. LA - eng PT - Journal Article DEP - 20221201 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - PJ788634QY (ginsenoside Rg1) RN - 0 (Ginsenosides) RN - 0 (Glutamates) SB - IM MH - Animals MH - Rats MH - *Ginsenosides/pharmacology/therapeutic use MH - Neuroinflammatory Diseases MH - Hippocampus MH - *Heart Arrest/complications/drug therapy MH - Cognition MH - Glutamates/pharmacology OTO - NOTNLM OT - Cardiac arrest OT - Cognition OT - Ginsenoside-Rg1 OT - Hippocampus OT - Neuroinflammation OT - Neuroplasticity COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/12/05 06:00 MHDA- 2022/12/20 06:00 CRDT- 2022/12/04 19:23 PHST- 2022/08/21 00:00 [received] PHST- 2022/11/25 00:00 [revised] PHST- 2022/11/28 00:00 [accepted] PHST- 2022/12/05 06:00 [pubmed] PHST- 2022/12/20 06:00 [medline] PHST- 2022/12/04 19:23 [entrez] AID - S0014-2999(22)00692-6 [pii] AID - 10.1016/j.ejphar.2022.175431 [doi] PST - ppublish SO - Eur J Pharmacol. 2023 Jan 5;938:175431. doi: 10.1016/j.ejphar.2022.175431. Epub 2022 Dec 1.