Propofol reduces microglia activation and neurotoxicity through inhibition of extracellular vesicle release

Jianhui Liu; Yuju Li; Xiaohuan Xia; Xiaoyu Yang; Runze Zhao; Justin Peer; Hongyun Wang; Zenghan Tong; Fengtong Gao; Hai Lin; Beiqing Wu; Yunlong Huang; Jialin C Zheng

doi:10.1016/j.jneuroim.2019.05.003

Propofol reduces microglia activation and neurotoxicity through inhibition of extracellular vesicle release

J Neuroimmunol. 2019 Aug 15:333:476962. doi: 10.1016/j.jneuroim.2019.05.003. Epub 2019 May 4.

[Article in French]

Authors

Jianhui Liu¹, Yuju Li², Xiaohuan Xia³, Xiaoyu Yang⁴, Runze Zhao⁵, Justin Peer⁵, Hongyun Wang⁵, Zenghan Tong⁵, Fengtong Gao⁵, Hai Lin⁵, Beiqing Wu⁵, Yunlong Huang⁶, Jialin C Zheng⁷

Affiliations

¹ Department of Anesthesiology, Tongji Hospital affiliated to Tongji University School of Medicine, Shanghai, China; Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, United States.
² Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital affiliated to Tongji University School of Medicine, Shanghai, China; Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, United States.
³ Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital affiliated to Tongji University School of Medicine, Shanghai, China.
⁴ Department of Anesthesiology, Tongji Hospital affiliated to Tongji University School of Medicine, Shanghai, China.
⁵ Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, United States.
⁶ Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital affiliated to Tongji University School of Medicine, Shanghai, China; Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, United States. Electronic address: yhuan1@unmc.edu.
⁷ Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital affiliated to Tongji University School of Medicine, Shanghai, China; Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, United States. Electronic address: jialinzheng@tongji.edu.cn.

Abstract

Propofol is an established anesthetic widely used for induction and maintenance of anesthesia. We investigated propofol for its anti-inflammatory effects on microglia and found that propofol treatment is associated with substantial lower levels of extracellular vesicles (EVs) in immune activated microglia. Importantly, EVs collected from immune activated microglia reversed propofol-mediated anti-inflammatory and neuroprotective effects, suggesting that propofol reduces proinflammatory microglia activation and microglia-mediated neurotoxicity through inhibition of EV release. These data shed new insight into a novel molecular mechanism of propofol-mediated neuroprotective and immunomodulatory effects through inhibition of EV release.

Keywords: Anesthetics; Extracellular vesicles; Microglia; Neuroinflammation; Neurotoxicity; Propofol.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Anti-Inflammatory Agents / pharmacology*
Cell Line
Cell Line, Tumor
Culture Media, Conditioned
Culture Media, Serum-Free
Extracellular Vesicles / drug effects*
Humans
Inflammation
Lipopolysaccharides / pharmacology
Microglia / drug effects*
Neuroblastoma / pathology
Neuroprotective Agents / pharmacology*
Propofol / pharmacology*

Substances

Anti-Inflammatory Agents
Culture Media, Conditioned
Culture Media, Serum-Free
Lipopolysaccharides
Neuroprotective Agents
Propofol

Grants and funding

R01 NS097195/NS/NINDS NIH HHS/United States