Ginsenoside-Rg1 mitigates cardiac arrest-induced cognitive damage by modulating neuroinflammation and hippocampal plasticity.

Abstract

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-1β (IL-1β) and tumour necrosis factor-α (TNF-α). 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.

• Authors: Zhangbi Wu, Jialin Huang, Xiaojie Bai, Qunan Wang, Fen Wang, Jun Xu, Huiping Tang, Chunying Yin, Yu Wang, Feng Yu, Hong Zhang
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 938 Pg. 175431 (Jan 05 2023) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 36463944 (Publication Type: Journal Article)
• Copyright: Copyright © 2022. Published by Elsevier B.V.

Chemical References

• ginsenoside Rg1
• Ginsenosides
• Glutamates

Topics

• Animals
• Rats
• Ginsenosides (pharmacology, therapeutic use)
• Neuroinflammatory Diseases
• Hippocampus
• Heart Arrest (complications, drug therapy)
• Cognition
• Glutamates (pharmacology)