Animal Models for Neuroinflammation and Potential Treatment Methods

Tamura, Yasuhisa; Yamato, Masayuki; Kataoka, Yosky

doi:10.3389/fneur.2022.890217

Cited by 14 publications

(5 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, peripheral administration of 6-MSITC also has central effects. For example, it inhibits neuroinflammation caused by intraperitoneal administration of polyinosinic:polycytidylic acid (polyI:C), a viral infection model [ 13 ], and has neuroprotective effects on nigral dopaminergic [ 10 ] and hippocampal neurons [ 12 ]. 6-MSITC also improves cognitive function.…”

Section: Discussionmentioning

confidence: 99%

“…In the rhizome of the wasabi plant there is a sulfinyl compound, called 6-methylsulfinylhexyl isothiocyanate (6-MSITC). In laboratory animals, 6-MSITC has been demonstrated to have anti-inflammatory [ 7 , 8 ], anti-allergenic [ 9 ], and antioxidant [ 10 – 12 ] effects, as well as to inhibit neuroinflammation [ 13 ]. It has also been shown to improve cognitive function [ 12 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Clinical effects of wasabi extract containing 6-MSITC on myalgic encephalomyelitis/chronic fatigue syndrome: an open-label trial

Oka

Yamada

Lkhagvasuren

et al. 2022

BioPsychoSocial Med

View full text Add to dashboard Cite

Background Wasabi (Eutrema japonicum) is a common pungent spice used in Japan. 6-Methylsulfinylhexyl isothiocyanate (6-MSITC) found in the rhizome of wasabi has been shown to have anti-inflammatory and antioxidant effects, as well as improve neuroinflammation and memory. Therefore, we hypothesized that these effects would be beneficial for treating myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The present study was conducted to investigate the effectiveness of wasabi extract containing 6-MSITC on ME/CFS in an open-label trial. Methods Fifteen patients (3 males, 12 females, 20–58 years old) were orally administered wasabi extract (9.6 mg of 6-MSITC/day) for 12 weeks. The following parameters and test results were compared pre- and post-treatment: performance status (PS), self-rating questionnaires, pressure pain threshold (PPT) on the occiput, Trail Making test-A (TMT-A), and hemodynamic patterns determined by an active standing test. Results After treatment with 6-MSITC, PS improved significantly (p = 0.001). Although the scores on the 11-item Chalder Fatigue scale (CFS-11) and numerical rating scale (NRS) of fatigue did not show significant changes, subjective symptoms improved significantly, including headache frequency (4.1 to 3.0 times/week, p = 0.001) and myalgia (4.1 to 2.4 times/week, p = 0.019), NRS brain fog scores (5.7 to 4.5, p = 0.011), difficulty finding appropriate words (4.8 to 3.7, p = 0.015), photophobia (4.8 to 3.5, p = 0.008), and the Profile of Mood Status vigor score (46.9 to 50.0, p = 0.045). The PPT of the right occiput (17.3 to 21.3 kPa, p = 0.01) and TMT-A scores (53.0 to 38.1 s, p = 0.007) also changed, suggesting reduced pain sensitivity, and improved cognitive function, respectively. Orthostatic patterns determined by a standing test did not show remarkable changes. There were no serious adverse reactions. Conclusion This study suggests that 6-MSITC improves PS as well as subjective symptoms such as pain and cognitive dysfunction, and psychological vitality of patients with ME/CFS. It also improved cognitive performance and increased pain thresholds in these patients. 6-MSITC may be a promising therapeutic option especially for improving cognitive dysfunction associated with ME/CFS.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical effects of wasabi extract containing 6-MSITC on myalgic encephalomyelitis/chronic fatigue syndrome: an open-label trial

Oka

Yamada

Lkhagvasuren

et al. 2022

BioPsychoSocial Med

View full text Add to dashboard Cite

show abstract

“…Animal models also provide proof-of-principle evidence of a hypothetical pathological mechanism for ME/CFS [18]. Efforts were also conducted to develop a mouse model for ME/CFS, using lipopolysaccharide challenges [68,69]. However, it is unclear how these models really mimic the main disease symptoms, especially post-exertional malaise.…”

Section: Ebv Antigenic Mimicry and Itsmentioning

confidence: 99%

IgG Antibody Responses to Epstein-Barr Virus in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Their Effective Potential for Disease Diagnosis and Pathological Antigenic Mimicry

Fonseca,

Szysz,

et al. 2024

Medicina

View full text Add to dashboard Cite

Background and Objectives: The diagnosis and pathology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) remain under debate. However, there is a growing body of evidence for an autoimmune component in ME/CFS caused by the Epstein-Barr virus (EBV) and other viral infections. Materials and Methods: In this work, we analyzed a large public dataset on the IgG antibodies to 3054 EBV peptides to understand whether these immune responses could help diagnose patients and trigger pathological autoimmunity; we used healthy controls (HCs) as a comparator cohort. Subsequently, we aimed at predicting the disease status of the study participants using a super learner algorithm targeting an accuracy of 85% when splitting data into train and test datasets. Results: When we compared the data of all ME/CFS patients or the data of a subgroup of those patients with non-infectious or unknown disease triggers to the data of the HC, we could not find an antibody-based classifier that would meet the desired accuracy in the test dataset. However, we could identify a 26-antibody classifier that could distinguish ME/CFS patients with an infectious disease trigger from the HCs with 100% and 90% accuracies in the train and test sets, respectively. We finally performed a bioinformatic analysis of the EBV peptides associated with these 26 antibodies. We found no correlation between the importance metric of the selected antibodies in the classifier and the maximal sequence homology between human proteins and each EBV peptide recognized by these antibodies. Conclusions: In conclusion, these 26 antibodies against EBV have an effective potential for disease diagnosis in a subset of patients. However, the peptides associated with these antibodies are less likely to induce autoimmune B-cell responses that could explain the pathogenesis of ME/CFS.

show abstract

“…To elucidate the pathogenesis of these debilitating diseases, several rodent models of inflammation-induced mental disorders have been developed ( Nazem et al, 2015 ; Na and Krishnamoorthy, 2021 ; Tamura et al, 2022 ). Among these models, systemic administration of lipopolysaccharide (LPS), a bacterial toxin, is often used, and LPS-injected mice exhibit abnormalities such as depressive-, anxiety-, and cognitive disorder-like behavior with neuroinflammation in some contexts ( Song and Wang, 2011 ; Hoogland et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Short-term memory impairment following recovery from systemic inflammation induced by lipopolysaccharide in mice

Morimoto,

Watanuki,

Eguchi

et al. 2023

Front. Neurosci.

View full text Add to dashboard Cite

The relationship between neuroinflammation and mental disorders has been recognized and investigated for over 30 years. Diseases of systemic or peripheral inflammation, such as sepsis, peritonitis, and infection, are associated with increased risk of mental disorders with neuroinflammation. To elucidate the pathogenesis, systemic administration of lipopolysaccharide (LPS) in mice is often used. LPS-injected mice exhibit behavioral abnormalities with glial activation. However, these studies are unlikely to recapitulate the clinical pathophysiology of human patients, as most studies focus on the acute inflammatory response with systemic symptoms occurring within 24 h of LPS injection. In this study, we focus on the effects of LPS on behavioral abnormalities following recovery from systemic symptoms and investigate the mechanisms of pathogenesis. Several behavioral tests were performed in LPS-injected mice, and to assess neuroinflammation, the time course of the morphological change and expression of inflammatory factors in neurons, astrocytes, and microglia were investigated. At 7 days post-LPS injection, mice exhibited short-term memory impairment accompanied by the suppression of neuronal activity and increases in morphologically immature spines. Glial cells were transiently activated in the hippocampus concomitant with upregulation of the microglial phagocytosis marker CD68 3 days after injection. Here we show that transient glial cell activation in the acute response phase affects neuronal activity and behavior following recovery from systemic symptoms. These findings provide novel insights for studies using the LPS-induced inflammation model and that will contribute to the development of treatments for mental disorders of this etiology.

show abstract

Animal Models for Neuroinflammation and Potential Treatment Methods

Cited by 14 publications

References 66 publications

Clinical effects of wasabi extract containing 6-MSITC on myalgic encephalomyelitis/chronic fatigue syndrome: an open-label trial

Clinical effects of wasabi extract containing 6-MSITC on myalgic encephalomyelitis/chronic fatigue syndrome: an open-label trial

IgG Antibody Responses to Epstein-Barr Virus in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Their Effective Potential for Disease Diagnosis and Pathological Antigenic Mimicry

Short-term memory impairment following recovery from systemic inflammation induced by lipopolysaccharide in mice

Contact Info

Product

Resources

About