Remimazolam attenuated lipopolysaccharide-induced behavioral deficits and neuronal injury via activation of the Nrf2 pathway
Abstract Sepsis is a severe disorder that is always accompanied by brain injury and dysfunction. This study aimed to evaluate the effects of remimazolam, a new ultra-short-acting sedative, on LPS-induced neuronal injury, and the role of Nrf2 signaling pathway involved. LPS was administered to Spragu...
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Nature Portfolio
2025-04-01
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| author | Yi Wei Sining Pan Zhan Zhou Ying Yang Tianxiao Liu Jing Chen Yubo Xie |
| author_facet | Yi Wei Sining Pan Zhan Zhou Ying Yang Tianxiao Liu Jing Chen Yubo Xie |
| author_sort | Yi Wei |
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| description | Abstract Sepsis is a severe disorder that is always accompanied by brain injury and dysfunction. This study aimed to evaluate the effects of remimazolam, a new ultra-short-acting sedative, on LPS-induced neuronal injury, and the role of Nrf2 signaling pathway involved. LPS was administered to Sprague-Dawley rats in the presence or absence of remimazolam. Then the behavior analysis was performed by using the Morris Water Maze and Open Field Test. The levels of the Superoxide Dismutase (SOD) and Malondialdehyde (MDA), the neuronal apoptosis, and the expression of Nrf2, HO-1, and Bcl-2 were detected in the hippocampus. In vitro, primary hippocampal neurons were exposed to LPS with or without remimazolam administration. Then the cell viability, apoptosis, mitochondrial membrane potential (MMP), and intracellular ROS were measured to assess oxidative stress and neuron injury. The expression of Nrf2, and HO-1 was also determined by Western blotting. LPS triggered neuroapoptosis, evoked oxidative stress, and inhibited the expression of Nrf2, and HO-1 in rat hippocampus, which were attenuated by remimazolam treatment. Additionally, remimazolam alleviated LPS-induced cognitive dysfunction and anxiety‑like behaviors in rats. In vitro, remimazolam could ameliorate neuronal damage, decrease the production of ROS, and increase the MMP of neurons exposed to LPS, which was accompanied by an increase in the expression of Nrf2 and HO-1. However, ML385 (an Nrf2 inhibitor) reversed the beneficial effects of remimazolam on primary hippocampal neurons. These findings suggest that remimazolam exerted protective effects on LPS-induced hippocampal neuronal injury in vivo and in vitro, which was associated with activation of Nrf2 signaling. Further experiments are needed to fully explore the exact molecular mechanism of Nrf2 upstream and downstream of remimazolam and its effects on distinct brain regions, which will help to better understand the neural effects of remimazolam. |
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| spelling | doaj-art-0f5b3d738fa64d91a64cd4d2316b61de2025-08-20T02:19:07ZengNature PortfolioScientific Reports2045-23222025-04-0115112310.1038/s41598-025-95379-yRemimazolam attenuated lipopolysaccharide-induced behavioral deficits and neuronal injury via activation of the Nrf2 pathwayYi Wei0Sining Pan1Zhan Zhou2Ying Yang3Tianxiao Liu4Jing Chen5Yubo Xie6Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Anesthesiology, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Anesthesiology, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Anesthesiology, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Anesthesiology, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Anesthesiology, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Anesthesiology, The First Affiliated Hospital of Guangxi Medical UniversityAbstract Sepsis is a severe disorder that is always accompanied by brain injury and dysfunction. This study aimed to evaluate the effects of remimazolam, a new ultra-short-acting sedative, on LPS-induced neuronal injury, and the role of Nrf2 signaling pathway involved. LPS was administered to Sprague-Dawley rats in the presence or absence of remimazolam. Then the behavior analysis was performed by using the Morris Water Maze and Open Field Test. The levels of the Superoxide Dismutase (SOD) and Malondialdehyde (MDA), the neuronal apoptosis, and the expression of Nrf2, HO-1, and Bcl-2 were detected in the hippocampus. In vitro, primary hippocampal neurons were exposed to LPS with or without remimazolam administration. Then the cell viability, apoptosis, mitochondrial membrane potential (MMP), and intracellular ROS were measured to assess oxidative stress and neuron injury. The expression of Nrf2, and HO-1 was also determined by Western blotting. LPS triggered neuroapoptosis, evoked oxidative stress, and inhibited the expression of Nrf2, and HO-1 in rat hippocampus, which were attenuated by remimazolam treatment. Additionally, remimazolam alleviated LPS-induced cognitive dysfunction and anxiety‑like behaviors in rats. In vitro, remimazolam could ameliorate neuronal damage, decrease the production of ROS, and increase the MMP of neurons exposed to LPS, which was accompanied by an increase in the expression of Nrf2 and HO-1. However, ML385 (an Nrf2 inhibitor) reversed the beneficial effects of remimazolam on primary hippocampal neurons. These findings suggest that remimazolam exerted protective effects on LPS-induced hippocampal neuronal injury in vivo and in vitro, which was associated with activation of Nrf2 signaling. Further experiments are needed to fully explore the exact molecular mechanism of Nrf2 upstream and downstream of remimazolam and its effects on distinct brain regions, which will help to better understand the neural effects of remimazolam.https://doi.org/10.1038/s41598-025-95379-yRemimazolamLPSNeurotoxicityOxidative stressNrf2 |
| spellingShingle | Yi Wei Sining Pan Zhan Zhou Ying Yang Tianxiao Liu Jing Chen Yubo Xie Remimazolam attenuated lipopolysaccharide-induced behavioral deficits and neuronal injury via activation of the Nrf2 pathway Scientific Reports Remimazolam LPS Neurotoxicity Oxidative stress Nrf2 |
| title | Remimazolam attenuated lipopolysaccharide-induced behavioral deficits and neuronal injury via activation of the Nrf2 pathway |
| title_full | Remimazolam attenuated lipopolysaccharide-induced behavioral deficits and neuronal injury via activation of the Nrf2 pathway |
| title_fullStr | Remimazolam attenuated lipopolysaccharide-induced behavioral deficits and neuronal injury via activation of the Nrf2 pathway |
| title_full_unstemmed | Remimazolam attenuated lipopolysaccharide-induced behavioral deficits and neuronal injury via activation of the Nrf2 pathway |
| title_short | Remimazolam attenuated lipopolysaccharide-induced behavioral deficits and neuronal injury via activation of the Nrf2 pathway |
| title_sort | remimazolam attenuated lipopolysaccharide induced behavioral deficits and neuronal injury via activation of the nrf2 pathway |
| topic | Remimazolam LPS Neurotoxicity Oxidative stress Nrf2 |
| url | https://doi.org/10.1038/s41598-025-95379-y |
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