Editorial

3 pages, 172 KiB

Open AccessEditorial

Inflammation in the CNS and PNS: From Molecular Basis to Therapy

by Savina Apolloni and Nadia D’Ambrosi

Int. J. Mol. Sci. 2023, 24(11), 9417; https://doi.org/10.3390/ijms24119417 - 29 May 2023

Viewed by 780

Our understanding of the pathophysiology of the nervous system has advanced significantly in the last few years, but there are still many unanswered questions [...] Full article

(This article belongs to the Special Issue Inflammation in the CNS and PNS: From Molecular Basis to Therapy)

Research

Jump to: Editorial, Review

20 pages, 3320 KiB

Open AccessArticle

Pioglitazone Attenuates the Effects of Peripheral Inflammation in a Human In Vitro Blood–Brain Barrier Model

by Gustavo Henrique Oliveira da Rocha, Rodrigo Azevedo Loiola, Marina de Paula-Silva, Fumitaka Shimizu, Takashi Kanda, Andrea Vieira, Fabien Gosselet and Sandra Helena Poliselli Farsky

Int. J. Mol. Sci. 2022, 23(21), 12781; https://doi.org/10.3390/ijms232112781 - 24 Oct 2022

Cited by 7 | Viewed by 1792

Abstract

Biological mediators secreted during peripheral chronic inflammation reach the bloodstream and may damage the blood–brain barrier (BBB), triggering central nervous system (CNS) disorders. Full-fledged human BBB models are efficient tools to investigate pharmacological pathways and mechanisms of injury at the BBB. We here [...] Read more.

Biological mediators secreted during peripheral chronic inflammation reach the bloodstream and may damage the blood–brain barrier (BBB), triggering central nervous system (CNS) disorders. Full-fledged human BBB models are efficient tools to investigate pharmacological pathways and mechanisms of injury at the BBB. We here employed a human in vitro BBB model to investigate the effects of either plasma from inflammatory bowel disease (IBD) patients or tumor necrosis factor α (TNFα), a cytokine commonly released in periphery during IBD, and the anti-inflammatory role of pioglitazone, a peroxisome proliferator-activated receptor γ agonist (PPARγ). The BBB model was treated with either 10% plasma from healthy and IBD donors or 5 ng/mL TNFα, following treatment with 10 µM pioglitazone. Patient plasma did not alter BBB parameters, but TNFα levels in plasma from all donors were associated with varying expression of claudin-5, claudin-3 and ICAM-1. TNFα treatment increased BBB permeability, claudin-5 disarrangement, VCAM-1 and ICAM-1 expression, MCP1 secretion and monocyte transmigration. These effects were attenuated by pioglitazone. Plasma from IBD patients, which evoked higher BBB permeability, also increased ICAM-1 expression, this effect being reversed by pioglitazone. Our findings evidence how pioglitazone controls periphery-elicited BBB inflammation and supports its repurposing for prevention/treating of such inflammatory conditions. Full article

(This article belongs to the Special Issue Inflammation in the CNS and PNS: From Molecular Basis to Therapy)

► Show Figures

Graphical abstract

12 pages, 3069 KiB

Open AccessArticle

Adhesion Molecule Profile and the Effect of Anti-VLA-4 mAb Treatment in Experimental Autoimmune Encephalomyelitis, a Mouse Model of Multiple Sclerosis

by Grażyna Pyka-Fościak, Grzegorz J. Lis and Jan A. Litwin

Int. J. Mol. Sci. 2022, 23(9), 4637; https://doi.org/10.3390/ijms23094637 - 22 Apr 2022

Cited by 5 | Viewed by 2045

Abstract

In the course of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), the infiltration of lymphocytes and other inflammatory cells across the blood–brain barrier is associated with interactions between adhesion molecules expressed by infiltrating cells and vascular endothelium. Monoclonal antibodies [...] Read more.

In the course of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), the infiltration of lymphocytes and other inflammatory cells across the blood–brain barrier is associated with interactions between adhesion molecules expressed by infiltrating cells and vascular endothelium. Monoclonal antibodies (mAb) against the α4 subunit of α4-β1 integrin (VLA-4) show beneficial effects in both MS and EAE. (1) Background: The aim of this study was to examine the expression of selected adhesion molecules: VLA-4, VCAM-1, LFA-1, ICAM-1 and PECAM-1 in the successive phases of EAE and the effect of anti-VLA-4 mAb treatment on that expression. (2) Methods: EAE was induced in C57BL/6 mice by immunization with MOG_35–55 peptide. The animals were killed in three successive phases of the disease: onset (day 13), peak (day 18) and chronic (day 28). Frozen sections of the lumbar spinal cord were examined by quantitative immunofluorescence microscopy. The expression of the studied molecules was quantified as the percentage of the cross-sectioned spinal cord lesion area occupied by immunopositive structures. (3) Results: The expression of the studied molecules showed two temporal patterns: (1) an increase in the onset phase, a maximum in the peak phase and a decrease in the chronic phase, which corresponded to the temporal pattern of the clinical score, the number of lesions and the inflammation level (ICAM-1, LFA-1 and PECAM-1), and (2) an increase in the peak phase and no significant change or further increase in the chronic phase (VCAM-1, VLA-4). Among the molecules studied, ICAM-1 and LFA-1 exhibited the highest expression levels in the peak phase of EAE. Anti-VLA-4 mAb inhibited the expression of not only VLA-4 but also other adhesion molecules. (4) Conclusions: The interactions of adhesion molecules governing the migration of leukocytes across the blood–brain barrier change in the successive phases of EAE. The therapeutic mechanism of anti-VLA-4 mAb treatment seems to include a complex influence on a variety of adhesion molecules expressed by infiltrating cells and vascular endothelium. Full article

(This article belongs to the Special Issue Inflammation in the CNS and PNS: From Molecular Basis to Therapy)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research

19 pages, 2956 KiB

Open AccessReview

Emerging Roles of Type-I Interferons in Neuroinflammation, Neurological Diseases, and Long-Haul COVID

by Ping-Heng Tan, Jasmine Ji, Chung-Hsi Hsing, Radika Tan and Ru-Rong Ji

Int. J. Mol. Sci. 2022, 23(22), 14394; https://doi.org/10.3390/ijms232214394 - 19 Nov 2022

Cited by 10 | Viewed by 4006

Abstract

Interferons (IFNs) are pleiotropic cytokines originally identified for their antiviral activity. IFN-α and IFN-β are both type I IFNs that have been used to treat neurological diseases such as multiple sclerosis. Microglia, astrocytes, as well as neurons in the central and peripheral nervous [...] Read more.

Interferons (IFNs) are pleiotropic cytokines originally identified for their antiviral activity. IFN-α and IFN-β are both type I IFNs that have been used to treat neurological diseases such as multiple sclerosis. Microglia, astrocytes, as well as neurons in the central and peripheral nervous systems, including spinal cord neurons and dorsal root ganglion neurons, express type I IFN receptors (IFNARs). Type I IFNs play an active role in regulating cognition, aging, depression, and neurodegenerative diseases. Notably, by suppressing neuronal activity and synaptic transmission, IFN-α and IFN-β produced potent analgesia. In this article, we discuss the role of type I IFNs in cognition, neurodegenerative diseases, and pain with a focus on neuroinflammation and neuro-glial interactions and their effects on cognition, neurodegenerative diseases, and pain. The role of type I IFNs in long-haul COVID-associated neurological disorders is also discussed. Insights into type I IFN signaling in neurons and non-neuronal cells will improve our treatments of neurological disorders in various disease conditions. Full article

(This article belongs to the Special Issue Inflammation in the CNS and PNS: From Molecular Basis to Therapy)

► Show Figures

Figure 1

11 pages, 653 KiB

Open AccessReview

Emerging Role of NLRP3 Inflammasome/Pyroptosis in Huntington’s Disease

by Emanuela Paldino and Francesca Romana Fusco

Int. J. Mol. Sci. 2022, 23(15), 8363; https://doi.org/10.3390/ijms23158363 - 28 Jul 2022

Cited by 10 | Viewed by 2539

Abstract

Huntington’s disease (HD) is a neurodegenerative disease characterized by several symptoms encompassing movement, cognition, and behavior. The mutation of the IT15 gene encoding for the huntingtin protein is the cause of HD. Mutant huntingtin interacts with and impairs the function of several transcription [...] Read more.

Huntington’s disease (HD) is a neurodegenerative disease characterized by several symptoms encompassing movement, cognition, and behavior. The mutation of the IT15 gene encoding for the huntingtin protein is the cause of HD. Mutant huntingtin interacts with and impairs the function of several transcription factors involved in neuronal survival. Although many mechanisms determining neuronal death have been described over the years, the significant role of inflammation has gained momentum in the last decade. Drugs targeting the elements that orchestrate inflammation have been considered powerful tools to treat HD. In this review, we will describe the data supporting inflammasome and NLRP3 as a target of therapeutics to fight HD, deepening the possible mechanisms of action underlying these effects. Full article

(This article belongs to the Special Issue Inflammation in the CNS and PNS: From Molecular Basis to Therapy)

► Show Figures

Figure 1

15 pages, 1037 KiB

Open AccessReview

Neuroimmune Crosstalk in Rheumatoid Arthritis

by Dashuang Gao, Xu Gao, Fan Yang and Qingwen Wang

Int. J. Mol. Sci. 2022, 23(15), 8158; https://doi.org/10.3390/ijms23158158 - 24 Jul 2022

Cited by 13 | Viewed by 3960

Abstract

Recent studies have demonstrated that immunological disease progression is closely related to abnormal function of the central nervous system (CNS). Rheumatoid arthritis (RA) is a chronic, inflammatory synovitis-based systemic immune disease of unknown etiology. In addition to joint pathological damage, RA has been [...] Read more.

Recent studies have demonstrated that immunological disease progression is closely related to abnormal function of the central nervous system (CNS). Rheumatoid arthritis (RA) is a chronic, inflammatory synovitis-based systemic immune disease of unknown etiology. In addition to joint pathological damage, RA has been linked to neuropsychiatric comorbidities, including depression, schizophrenia, and anxiety, increasing the risk of neurodegenerative diseases in life. Immune cells and their secreted immune factors will stimulate the peripheral and central neuronal systems that regulate innate and adaptive immunity. The understanding of autoimmune diseases has largely advanced insights into the molecular mechanisms of neuroimmune interaction. Here, we review our current understanding of CNS comorbidities and potential physiological mechanisms in patients with RA, with a focus on the complex and diverse regulation of mood and distinct patterns of peripheral immune activation in patients with rheumatoid arthritis. And in our review, we also discussed the role that has been played by peripheral neurons and CNS in terms of neuron mechanisms in RA immune challenges, and the related neuron-immune crosstalk. Full article

(This article belongs to the Special Issue Inflammation in the CNS and PNS: From Molecular Basis to Therapy)

► Show Figures

Figure 1

10 pages, 602 KiB

Open AccessReview

Neuroinflammation in Friedreich’s Ataxia

by Savina Apolloni, Martina Milani and Nadia D’Ambrosi

Int. J. Mol. Sci. 2022, 23(11), 6297; https://doi.org/10.3390/ijms23116297 - 04 Jun 2022

Cited by 11 | Viewed by 2878

Abstract

Friedreich’s ataxia (FRDA) is a rare genetic disorder caused by mutations in the gene frataxin, encoding for a mitochondrial protein involved in iron handling and in the biogenesis of iron−sulphur clusters, and leading to progressive nervous system damage. Although the overt manifestations of [...] Read more.

Friedreich’s ataxia (FRDA) is a rare genetic disorder caused by mutations in the gene frataxin, encoding for a mitochondrial protein involved in iron handling and in the biogenesis of iron−sulphur clusters, and leading to progressive nervous system damage. Although the overt manifestations of FRDA in the nervous system are mainly observed in the neurons, alterations in non-neuronal cells may also contribute to the pathogenesis of the disease, as recently suggested for other neurodegenerative disorders. In FRDA, the involvement of glial cells can be ascribed to direct effects caused by frataxin loss, eliciting different aberrant mechanisms. Iron accumulation, mitochondria dysfunction, and reactive species overproduction, mechanisms identified as etiopathogenic in neurons in FRDA, can similarly affect glial cells, leading them to assume phenotypes that can concur to and exacerbate neuron loss. Recent findings obtained in FRDA patients and cellular and animal models of the disease have suggested that neuroinflammation can accompany and contribute to the neuropathology. In this review article, we discuss evidence about the involvement of neuroinflammatory-related mechanisms in models of FRDA and provide clues for the modulation of glial-related mechanisms as a possible strategy to improve disease features. Full article

(This article belongs to the Special Issue Inflammation in the CNS and PNS: From Molecular Basis to Therapy)

► Show Figures

Figure 1

13 pages, 259 KiB

Open AccessReview

Efficacy of 5% Dextrose Water Injection for Peripheral Entrapment Neuropathy: A Narrative Review

by Yung-Tsan Wu, Chueh-Hung Wu, Jui-An Lin, Daniel Chiung-Jui Su, Chen-Yu Hung and Stanley K. H. Lam

Int. J. Mol. Sci. 2021, 22(22), 12358; https://doi.org/10.3390/ijms222212358 - 16 Nov 2021

Cited by 19 | Viewed by 5295

Abstract

Current non-surgical treatment for peripheral entrapment neuropathy is considered insignificant and unsustainable; thus, it is essential to find an alternative novel treatment. The technique of perineural injection therapy using 5% dextrose water has been progressively used to treat many peripheral entrapment neuropathies and [...] Read more.

Current non-surgical treatment for peripheral entrapment neuropathy is considered insignificant and unsustainable; thus, it is essential to find an alternative novel treatment. The technique of perineural injection therapy using 5% dextrose water has been progressively used to treat many peripheral entrapment neuropathies and has been proven to have outstanding effects in a few high-quality studies. Currently, the twentieth edition of Harrison’s Principles of Internal Medicine textbook recommends this novel injection therapy as an alternative local treatment for carpal tunnel syndrome (CTS). Hence, this novel approach has become the mainstream method for treating CTS, and other studies have revealed its clinical benefit for other peripheral entrapment neuropathies. In this narrative review, we aimed to provide an insight into this treatment method and summarize the current studies on cases of peripheral entrapment neuropathy treated by this method. Full article

(This article belongs to the Special Issue Inflammation in the CNS and PNS: From Molecular Basis to Therapy)

Journal Menu

Journal Browser

Inflammation in the CNS and PNS: From Molecular Basis to Therapy

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Published Papers (8 papers)

Editorial

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI