The Protective Effects of Ramelteon Against Isoflurane-Induced Insults and Inflammatory Response in Brain Microvascular
- PDF / 1,848,505 Bytes
- 10 Pages / 595.276 x 790.866 pts Page_size
- 51 Downloads / 182 Views
ORIGINAL ARTICLE
The Protective Effects of Ramelteon Against Isoflurane-Induced Insults and Inflammatory Response in Brain Microvascular Endothelial Cells Tao Wang 1 & Zhen Li 2 & Shuyun Xia 3 & Zhixin Xu 1 & Xiaofang Chen 1 & Hu Sun 1 Received: 21 September 2020 / Revised: 29 October 2020 / Accepted: 1 November 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Anesthetic-induced cognitive impairment has been observed clinically. The mechanism underlying anesthetic-induced cognitive impairment is closely associated with neuronal apoptosis and neuroinflammation. Ramelteon is a potent and highly selective melatonin receptor agonist that has been used for the treatment of insomnia and has been reported to have an anti-inflammatory effect. In this study, we aimed to investigate the protective effects of Ramelteon against the cytotoxicity induced by isoflurane in brain microvascular endothelial cells. Our results show that Ramelteon ameliorated oxidative stress by suppressing the generation of mitochondrial reactive oxygen species (ROS) in human brain microvascular endothelial cells (HBMVECs). In addition, Ramelteon displayed a robust anti-inflammatory capacity against isoflurane-induced insults and inflammation by reducing the generation of interleukin-1β (IL-1β), transforming growth factor-β (TGF-β), monocyte chemotactic protein 1 (MCP-1), stromal cell-derived factor-1 (SDF-1), matrix metalloproteinase-2 (MMP-2), and MMP-9. Furthermore, Ramelteon reduced the expression of cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and E-selectin. Importantly, Ramelteon downregulated the activation of the p38MAPK/NF-κB signaling pathway, which is the key transcriptional regulator in the inflammation process. Our findings in the present study provide new evidence for the use of Ramelteon in the prevention of isoflurane-induced insults in brain endothelial cells. Keywords Ramelteon . Isoflurane . Oxidative stress . Neuroinflammation . NF-κB . Brain endothelial cells
Introduction Isoflurane is a kind of halocarbon inhalation anesthetic, which is widely used in surgical procedures (Mohaghegh et al. 2017). The advantages of this anesthetic agent include fast induction of anesthesia, no stimulation, and rapid recovery. However, recent researches have shown the potential risks related to the use of isoflurane, especially the neuron damage
* Tao Wang [email protected] 1
Department of Anesthesiology, The Second Affiliated Hospital of Hainan Medical University, 368 Yehai Av., Longhua District, Haikou 570311, Hainan, China
2
Department of Anesthesiology, Qinghai Women’s and Children’s Hospital, Xi’ning, China
3
Department of Respiratory Medicine, Pingdu People’s Hospital, Pingdu, China
which develops in the brain, and impairs cognitive function (Wilder et al. 2009; Tao et al. 2016). Animal studies have demonstrated that isoflurane application is responsible for the apoptosis of neurons in rats, which results in cognitive impairment (Johnson et al. 2008; Stratmann et al. 2
Data Loading...
