Inflammation From Peripheral Organs to the Brain: How Does Systemic Inflammation Cause Neuroinflammation?

Overview

Journal Front Aging Neurosci

Specialty Geriatrics

Date 2022 Jul 5

PMID 35783147

Authors

Yuanjie Sun

Yoshihisa Koyama

Shoichi Shimada

Affiliations

Soon will be listed here.

Abstract

As inflammation in the brain contributes to several neurological and psychiatric diseases, the cause of neuroinflammation is being widely studied. The causes of neuroinflammation can be roughly divided into the following domains: viral infection, autoimmune disease, inflammation from peripheral organs, mental stress, metabolic disorders, and lifestyle. In particular, the effects of neuroinflammation caused by inflammation of peripheral organs have yet unclear mechanisms. Many diseases, such as gastrointestinal inflammation, chronic obstructive pulmonary disease, rheumatoid arthritis, dermatitis, chronic fatigue syndrome, or myalgic encephalomyelitis (CFS/ME), trigger neuroinflammation through several pathways. The mechanisms of action for peripheral inflammation-induced neuroinflammation include disruption of the blood-brain barrier, activation of glial cells associated with systemic immune activation, and effects on autonomic nerves via the organ-brain axis. In this review, we consider previous studies on the relationship between systemic inflammation and neuroinflammation, focusing on the brain regions susceptible to inflammation.

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References

Bath K, Schilit A, Lee F . Stress effects on BDNF expression: effects of age, sex, and form of stress. Neuroscience. 2013; 239:149-56. DOI: 10.1016/j.neuroscience.2013.01.074. View

Banks W . Blood-brain barrier transport of cytokines: a mechanism for neuropathology. Curr Pharm Des. 2005; 11(8):973-84. DOI: 10.2174/1381612053381684. View

Douet V, Tanizaki N, Franke A, Li X, Chang L . Polymorphism of Kynurenine Pathway-Related Genes, Kynurenic Acid, and Psychopathological Symptoms in HIV. J Neuroimmune Pharmacol. 2016; 11(3):549-61. PMC: 6502481. DOI: 10.1007/s11481-016-9668-7. View

Linnerbauer M, Wheeler M, Quintana F . Astrocyte Crosstalk in CNS Inflammation. Neuron. 2020; 108(4):608-622. PMC: 7704785. DOI: 10.1016/j.neuron.2020.08.012. View

Abautret-Daly A, Dempsey E, Parra-Blanco A, Medina C, Harkin A . Gut-brain actions underlying comorbid anxiety and depression associated with inflammatory bowel disease. Acta Neuropsychiatr. 2017; 30(5):275-296. DOI: 10.1017/neu.2017.3. View

Zenouzi R, von der Gablentz J, Heldmann M, Gottlich M, Weiler-Normann C, Sebode M . Patients with primary biliary cholangitis and fatigue present with depressive symptoms and selected cognitive deficits, but with normal attention performance and brain structure. PLoS One. 2018; 13(1):e0190005. PMC: 5761833. DOI: 10.1371/journal.pone.0190005. View

Yazdi A, Ghoreschi K . The Interleukin-1 Family. Adv Exp Med Biol. 2016; 941:21-29. DOI: 10.1007/978-94-024-0921-5_2. View

Reichmann F, Hassan A, Farzi A, Jain P, Schuligoi R, Holzer P . Dextran sulfate sodium-induced colitis alters stress-associated behaviour and neuropeptide gene expression in the amygdala-hippocampus network of mice. Sci Rep. 2015; 5:9970. PMC: 4464346. DOI: 10.1038/srep09970. View

Walker F, Beynon S, Jones K, Zhao Z, Kongsui R, Cairns M . Dynamic structural remodelling of microglia in health and disease: a review of the models, the signals and the mechanisms. Brain Behav Immun. 2014; 37:1-14. DOI: 10.1016/j.bbi.2013.12.010. View

10.

Hoogland I, Houbolt C, van Westerloo D, van Gool W, van de Beek D . Systemic inflammation and microglial activation: systematic review of animal experiments. J Neuroinflammation. 2015; 12:114. PMC: 4470063. DOI: 10.1186/s12974-015-0332-6. View

11.

He X, Li L, Xian W, Li M, Zhang L, Xu J . Chronic colitis exacerbates NLRP3-dependent neuroinflammation and cognitive impairment in middle-aged brain. J Neuroinflammation. 2021; 18(1):153. PMC: 8262017. DOI: 10.1186/s12974-021-02199-8. View

12.

Sudo N . Microbiome, HPA axis and production of endocrine hormones in the gut. Adv Exp Med Biol. 2014; 817:177-94. DOI: 10.1007/978-1-4939-0897-4_8. View

13.

Font-Nieves M, Sans-Fons M, Gorina R, Bonfill-Teixidor E, Salas-Perdomo A, Marquez-Kisinousky L . Induction of COX-2 enzyme and down-regulation of COX-1 expression by lipopolysaccharide (LPS) control prostaglandin E2 production in astrocytes. J Biol Chem. 2012; 287(9):6454-68. PMC: 3307308. DOI: 10.1074/jbc.M111.327874. View

14.

Rhea E, Banks W . Role of the Blood-Brain Barrier in Central Nervous System Insulin Resistance. Front Neurosci. 2019; 13:521. PMC: 6558081. DOI: 10.3389/fnins.2019.00521. View

15.

Abbott N, Patabendige A, Dolman D, Yusof S, Begley D . Structure and function of the blood-brain barrier. Neurobiol Dis. 2009; 37(1):13-25. DOI: 10.1016/j.nbd.2009.07.030. View

16.

Steinman L . Modulation of postoperative cognitive decline via blockade of inflammatory cytokines outside the brain. Proc Natl Acad Sci U S A. 2010; 107(48):20595-6. PMC: 2996451. DOI: 10.1073/pnas.1015282107. View

17.

Schrepf A, Kaplan C, Ichesco E, Larkin T, Harte S, Harris R . A multi-modal MRI study of the central response to inflammation in rheumatoid arthritis. Nat Commun. 2018; 9(1):2243. PMC: 5993749. DOI: 10.1038/s41467-018-04648-0. View

18.

Haj-Mirzaian A, Amiri S, Amini-Khoei H, Hosseini M, Haj-Mirzaian A, Momeny M . Anxiety- and Depressive-Like Behaviors are Associated with Altered Hippocampal Energy and Inflammatory Status in a Mouse Model of Crohn's Disease. Neuroscience. 2017; 366:124-137. DOI: 10.1016/j.neuroscience.2017.10.023. View

19.

Dolapcioglu C, Dolapcioglu H . Structural brain lesions in inflammatory bowel disease. World J Gastrointest Pathophysiol. 2015; 6(4):124-30. PMC: 4644876. DOI: 10.4291/wjgp.v6.i4.124. View

20.

Hanisch U, Kettenmann H . Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci. 2007; 10(11):1387-94. DOI: 10.1038/nn1997. View