Sepsis-associated Encephalopathy: Autophagy and MiRNAs Regulate Microglial Activation

Overview

Journal Physiol Rep

Specialty Physiology

Date 2024 Mar 5

PMID 38439741

Authors

Nannan Qin

Yanmei Miao

Leiyu Xie

Xinglong Ma

Peng Xie

Affiliations

Soon will be listed here.

Abstract

Sepsis-associated encephalopathy (SAE) describes diffuse or multifocal cerebral dysfunction caused by the systemic inflammatory response to sepsis. SAE is a common neurological complication in patients in the middle and late stages of sepsis in the intensive care unit. Microglia, resident macrophages of the central nervous system, phagocytose small numbers of neuronal cells and apoptotic cells, among other cells, to maintain the dynamic balance of the brain's internal environment. The neuroinflammatory response induced by activated microglia plays a central role in the pathogenesis of various central nervous system diseases. In this paper, we systematically describe the functions and phenotypes of microglia, summarize how microglia mediate neuroinflammation and contribute to the occurrence and development of SAE, and discuss recent progress in autophagy- and microRNA-mediated regulation of microglial activation to provide a theoretical basis for the prevention and treatment of SAE and identify related therapeutic targets.

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References

Shao B, Yao Y, Zhai J, Zhu J, Li J, Wu K . The Role of Autophagy in Inflammatory Bowel Disease. Front Physiol. 2021; 12:621132. PMC: 7902040. DOI: 10.3389/fphys.2021.621132. View

Jin X, Liu M, Zhang D, Zhong X, Du K, Qian P . Natural products as a potential modulator of microglial polarization in neurodegenerative diseases. Pharmacol Res. 2019; 145:104253. DOI: 10.1016/j.phrs.2019.104253. View

Morishita H, Mizushima N . Diverse Cellular Roles of Autophagy. Annu Rev Cell Dev Biol. 2019; 35:453-475. DOI: 10.1146/annurev-cellbio-100818-125300. View

Reinhart K, Karzai W, Meisner M . Procalcitonin as a marker of the systemic inflammatory response to infection. Intensive Care Med. 2000; 26(9):1193-200. PMC: 7095266. DOI: 10.1007/s001340000624. View

Hegdekar N, Sarkar C, Bustos S, Ritzel R, Hanscom M, Ravishankar P . Inhibition of autophagy in microglia and macrophages exacerbates innate immune responses and worsens brain injury outcomes. Autophagy. 2023; 19(7):2026-2044. PMC: 10283445. DOI: 10.1080/15548627.2023.2167689. View

Li B, Dasgupta C, Huang L, Meng X, Zhang L . MiRNA-210 induces microglial activation and regulates microglia-mediated neuroinflammation in neonatal hypoxic-ischemic encephalopathy. Cell Mol Immunol. 2019; 17(9):976-991. PMC: 7608107. DOI: 10.1038/s41423-019-0257-6. View

Orihuela R, McPherson C, Harry G . Microglial M1/M2 polarization and metabolic states. Br J Pharmacol. 2015; 173(4):649-65. PMC: 4742299. DOI: 10.1111/bph.13139. View

Shen Y, Zhang Y, Du J, Jiang B, Shan T, Li H . CXCR5 down-regulation alleviates cognitive dysfunction in a mouse model of sepsis-associated encephalopathy: potential role of microglial autophagy and the p38MAPK/NF-κB/STAT3 signaling pathway. J Neuroinflammation. 2021; 18(1):246. PMC: 8554863. DOI: 10.1186/s12974-021-02300-1. View

Leli C, Ferranti M, Marrano U, Al Dhahab Z, Bozza S, Cenci E . Diagnostic accuracy of presepsin (sCD14-ST) and procalcitonin for prediction of bacteraemia and bacterial DNAaemia in patients with suspected sepsis. J Med Microbiol. 2016; 65(8):713-719. DOI: 10.1099/jmm.0.000278. View

10.

Iwashyna T, Wesley Ely E, Smith D, Langa K . Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010; 304(16):1787-94. PMC: 3345288. DOI: 10.1001/jama.2010.1553. View

11.

Maiese A, Scatena A, Costantino A, Chiti E, Occhipinti C, La Russa R . Expression of MicroRNAs in Sepsis-Related Organ Dysfunction: A Systematic Review. Int J Mol Sci. 2022; 23(16). PMC: 9409129. DOI: 10.3390/ijms23169354. View

12.

Sheng B, Zhao L, Zang X, Zhen J, Chen W . miR-375 ameliorates sepsis by downregulating miR-21 level via inhibiting JAK2-STAT3 signaling. Biomed Pharmacother. 2016; 86:254-261. DOI: 10.1016/j.biopha.2016.11.147. View

13.

Kierdorf K, Prinz M . Microglia in steady state. J Clin Invest. 2017; 127(9):3201-3209. PMC: 5669563. DOI: 10.1172/JCI90602. View

14.

Feng H, Cui Y, Liu J, Liu M, Zhou W, Yan Z . Effects of 3-Methyladenine on Microglia Autophagy and Neuronal Apoptosis After Radiation-Induced Brain Injury. Dose Response. 2022; 20(2):15593258221100593. PMC: 9125074. DOI: 10.1177/15593258221100593. View

15.

Paolicelli R, Bolasco G, Pagani F, Maggi L, Scianni M, Panzanelli P . Synaptic pruning by microglia is necessary for normal brain development. Science. 2011; 333(6048):1456-8. DOI: 10.1126/science.1202529. View

16.

Errede M, Annese T, Petrosino V, Longo G, Girolamo F, De Trizio I . Microglia-derived CCL2 has a prime role in neocortex neuroinflammation. Fluids Barriers CNS. 2022; 19(1):68. PMC: 9429625. DOI: 10.1186/s12987-022-00365-5. View

17.

Ke X, Deng M, Wu Z, Yu H, Yu D, Li H . miR-34b-3p Inhibition of eIF4E Causes Post-stroke Depression in Adult Mice. Neurosci Bull. 2022; 39(2):194-212. PMC: 9905405. DOI: 10.1007/s12264-022-00898-7. View

18.

Zhang Z, Zhang Z, Lu H, Yang Q, Wu H, Wang J . Microglial Polarization and Inflammatory Mediators After Intracerebral Hemorrhage. Mol Neurobiol. 2016; 54(3):1874-1886. PMC: 4991954. DOI: 10.1007/s12035-016-9785-6. View

19.

Moraes C, Zaverucha-do-Valle C, Fleurance R, Sharshar T, Bozza F, Costa DAvila J . Neuroinflammation in Sepsis: Molecular Pathways of Microglia Activation. Pharmaceuticals (Basel). 2021; 14(5). PMC: 8147235. DOI: 10.3390/ph14050416. View

20.

Lei L, Cheng A, Wang M, Jia R . The Influence of Host miRNA Binding to RNA Within RNA Viruses on Virus Multiplication. Front Cell Infect Microbiol. 2022; 12:802149. PMC: 9069554. DOI: 10.3389/fcimb.2022.802149. View