IL-6 Induced by Periodontal Inflammation Causes Neuroinflammation and Disrupts the Blood–Brain Barrier

Furutama, Daisuke; Matsuda, Shinji; Yamawaki, Yosuke; Hatano, Saki; Okanobu, Ai; Memida, Takumi; Oue, Hiroshi; Fujita, Tsuyoshi; Ouhara, Kazuhisa; Kajiya, Mikihito; Mizuno, Noriyoshi; Kanematsu, Takashi; Tsuga, Kazuhiro; Kurihara, Hidemi

doi:10.3390/brainsci10100679

Cited by 32 publications

(32 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To explain gliosis, they proposed a hypothesis that inflammatory cytokines and toxins damaged the BBB during the pathogenesis of periodontitis. Subsequently, another research group applied a 7-0 silk ligature, proved the hypothesis, and showed that the permeability of the BBB increased when periodontitis was induced in similar mice [118]. Moreover, if ligature placement was prolonged to one year, the mice showed signs of cognitive impairment in addition to neural inflammation [119].…”

Section: Effect On the Central Nervous Systemmentioning

confidence: 94%

Application of Ligature-Induced Periodontitis in Mice to Explore the Molecular Mechanism of Periodontal Disease

Lin

Niimi

Ohsugi

et al. 2021

IJMS

View full text Add to dashboard Cite

Periodontitis is an inflammatory disease characterized by the destruction of the periodontium. In the last decade, a new murine model of periodontitis has been widely used to simulate alveolar bone resorption and periodontal soft tissue destruction by ligation. Typically, 3-0 to 9-0 silks are selected for ligation around the molars in mice, and significant bone loss and inflammatory infiltration are observed within a week. The ligature-maintained period can vary according to specific aims. We reviewed the findings on the interaction of systemic diseases with periodontitis, periodontal tissue destruction, the immunological and bacteriological responses, and new treatments. In these studies, the activation of osteoclasts, upregulation of pro-inflammatory factors, and excessive immune response have been considered as major factors in periodontal disruption. Multiple genes identified in periodontal tissues partly reflect the complexity of the pathogenesis of periodontitis. The effects of novel treatment methods on periodontitis have also been evaluated in a ligature-induced periodontitis model in mice. This model cannot completely represent all aspects of periodontitis in humans but is considered an effective method for the exploration of its mechanisms. Through this review, we aimed to provide evidence and enlightenment for future studies planning to use this model.

show abstract

Section: Effect On the Central Nervous Systemmentioning

confidence: 94%

Application of Ligature-Induced Periodontitis in Mice to Explore the Molecular Mechanism of Periodontal Disease

Lin

Niimi

Ohsugi

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…; Sc, Streptococcus constellatus. References: [A] : Cardoso et al ( 2018 ); [B] : Bui et al ( 2019 ), [C] : Fine et al ( 2020 ), [D] : Gallimidi et al ( 2015 ), [E] : Ha et al ( 2015 ), [F] : Lamster and Pagan ( 2017 ), [G] : Jepsen et al ( 2020 ), [H] : Minty et al ( 2019 ), [I] : Torrungruang et al ( 2018 ), [J] : Suh et al ( 2019 ), [K] : Schenkein et al ( 2020 ), [L] : Singhal et al ( 2016 ), [M] : Cecoro et al ( 2020 ), [N] : Baeza et al ( 2020 ), [O] : Furutama et al ( 2020 ), [P] : Ferguson et al ( 2020 ) [Q] : Preshaw et al ( 2020 ), [R] : Sukumar and Tadepalli ( 2021 ), [S] : Badran et al ( 2020 ), [T] : Coke et al ( 2021 ), [U] : Han and Wang ( 2013 ), [V] : González-Febles and Sanz ( 2021 ), [W] : Maldonado et al ( 2020 ), [X] : Bunte and Beikler ( 2019 ), [Y] : Poole et al ( 2013 ), [Z] : Poole et al ( 2015 ), [Aa] : Stein et al ( 2012 ), [Ab] : Bobetsis et al ( 2020 ) .…”

Section: Medical Aspects Of Periodontal Inflammationmentioning

confidence: 99%

“…Sustained periodontal inflammatory states will alter the count of circulating neutrophils due to increased bone marrow output or mobilization of the marginal granulocyte pool (Cecoro et al, 2020 ). Uptake of advanced glycation end products (AGEs) during PD is reported to drive pro-inflammatory signals that, in turn, trigger redox-sensitive transcription factors deemed responsible for hyper-permeability of the endothelial cell, VCAM-1 (vascular cell adhesion molecule 1) activation, chemotaxis and the release of TNF, IL-1, IL-6 into the bloodstream (Furutama et al, 2020 ). These circulating inflammatory mediators are able then to modify endothelial function, leading to impaired vasodilation and causing significant alterations in the vascular structure (Cecoro et al, 2020 ).…”

Section: Medical Aspects Of Periodontal Inflammationmentioning

confidence: 99%

“…Depression—which is more properly described as a psychiatric ailment than a neurological disease—has also been associated with system-wide inflammatory processes and chronic periodontitis (Hashioka et al, 2018 ) involving the so called neuroinflammation processes ( Table 3 ; Teixeira et al, 2017 ; Furutama et al, 2020 ).…”

Section: Medical Aspects Of Periodontal Inflammationmentioning

confidence: 99%

See 1 more Smart Citation

Periodontal Inflammation and Systemic Diseases: An Overview

2021

View full text Add to dashboard Cite

Periodontitis is a common inflammatory disease of infectious origins that often evolves into a chronic condition. Aside from its importance as a stomatologic ailment, chronic periodontitis has gained relevance since it has been shown that it can develop into a systemic condition characterized by unresolved hyper-inflammation, disruption of the innate and adaptive immune system, dysbiosis of the oral, gut and other location's microbiota and other system-wide alterations that may cause, coexist or aggravate other health issues associated to elevated morbi-mortality. The relationships between the infectious, immune, inflammatory, and systemic features of periodontitis and its many related diseases are far from being fully understood and are indeed still debated. However, to date, a large body of evidence on the different biological, clinical, and policy-enabling sources of information, is available. The aim of the present work is to summarize many of these sources of information and contextualize them under a systemic inflammation framework that may set the basis to an integral vision, useful for basic, clinical, and therapeutic goals.

show abstract

“…Rather, there is a bidirectional intricate communication between the periphery and the CNS. In ammation in the periphery can interfere with the blood-brain barrier (BBB) integrity and induce changes in the brain [13,14].…”

Section: Introductionmentioning

confidence: 99%

Primary Peripheral Epstein-Barr Virus Infection Can Lead to CNS Infection and Neuroinflammation in a Rabbit Model: Implications for Multiple Sclerosis Pathogenesis

Hassani

Reguraman

Shehab

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Epstein-Barr virus (EBV) is a common herpesvirus associated with malignant and non-malignant conditions. An accumulating body of evidence supports a role for EBV in the pathogenesis of multiple sclerosis (MS), a demyelinative disease of the CNS. However, little is known about the details of the link between EBV and MS. One obstacle which has hindered research in this area has been the lack of a suitable animal model recapitulating natural infection in humans. We have recently shown that healthy rabbits are susceptible to EBV infection, and viral persistence in these animals mimics latent infection in humans. Methods: We used the rabbit model to investigate if peripheral EBV infection can lead to infection of the CNS and its potential consequences. We injected EBV intravenously in one group of animals, and PBS in another, with and without immunosuppression. Histopathological changes and viral dynamics were examined in peripheral blood, spleen, brain, and spinal cord, using a range of molecular and histopathology techniques. Results: Our investigations uncovered important findings that could not be previously addressed. We showed that primary peripheral EBV infection can lead to the virus traversing the CNS. Cell associated, but not free virus in the plasma, correlated with CNS infection. The infected cells within the brain were found to be B-lymphocytes. Most notably, animals injected with EBV, but not PBS, developed inflammatory cellular aggregates in the CNS. The incidence of these aggregates increased in the immunosuppressed animals. The cellular aggregates contained compact clusters of macrophages surrounded by reactive astrocytes and dispersed B and T lymphocytes, but not myelinated nerve fibers. Moreover, studying EBV infection over a span of 28 days, revealed that the peak point for viral load in the periphery and CNS coincides with increased occurrence of cellular aggregates in the brain. Finally, peripheral EBV infection triggered temporal changes in the expression of latent viral transcripts and cytokines in the brain. Conclusion: The present study provides the first direct in vivo evidence for the role of peripheral EBV infection in CNS pathology, and highlights a unique model to dissect viral mechanisms contributing to the development of MS.

show abstract

IL-6 Induced by Periodontal Inflammation Causes Neuroinflammation and Disrupts the Blood–Brain Barrier

Cited by 32 publications

References 60 publications

Application of Ligature-Induced Periodontitis in Mice to Explore the Molecular Mechanism of Periodontal Disease

Application of Ligature-Induced Periodontitis in Mice to Explore the Molecular Mechanism of Periodontal Disease

Periodontal Inflammation and Systemic Diseases: An Overview

Primary Peripheral Epstein-Barr Virus Infection Can Lead to CNS Infection and Neuroinflammation in a Rabbit Model: Implications for Multiple Sclerosis Pathogenesis

Contact Info

Product

Resources

About