Elevated CSF histamine levels in multiple sclerosis patients

Kallweit, Ulf; Aritake, Kosuke; Bassetti, Claudio; Blumenthal, Stephan; Hayaishi, Osamu; Linnebank, Michael; Baumann, Christian R.; Urade, Yoshihiro

doi:10.1186/2045-8118-10-19

Cited by 26 publications

(15 citation statements)

References 15 publications

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“…Elevated levels of mast cell products have been detected in fluids from MS patients. These include mast cell tryptase in CSF from MS patients [ 60 ] and histamine levels in CSF from MS patients [ 61 , 62 ]. In spite of such evidence, the role of mast cells in MS is still somewhat controversial [ 63 ], in part because some mouse models of MS, such as induced EAE, have indicated that while mast cells can accumulate in EAE, they are “dispensable” [ 64 ].…”

Section: Multiple Sclerosismentioning

confidence: 99%

Curbing Inflammation in Multiple Sclerosis and Endometriosis: Should Mast Cells Be Targeted?

Hart

2015

International Journal of Inflammation

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Inflammatory diseases and conditions can arise due to responses to a variety of external and internal stimuli. They can occur acutely in response to some stimuli and then become chronic leading to tissue damage and loss of function. While a number of cell types can be involved, mast cells are often present and can be involved in the acute and chronic processes. Recent studies in porcine and rabbit models have supported the concept of a central role for mast cells in a “nerve-mast cell-myofibroblast axis” in some inflammatory processes leading to fibrogenic outcomes. The current review is focused on the potential of extending aspects of this paradigm into treatments for multiple sclerosis and endometriosis, diseases not usually thought of as having common features, but both are reported to have activation of mast cells involved in their respective disease processes. Based on the discussion, it is proposed that targeting mast cells in these diseases, particularly the early phases, may be a fruitful avenue to control the recurring inflammatory exacerbations of the conditions.

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Section: Multiple Sclerosismentioning

confidence: 99%

Curbing Inflammation in Multiple Sclerosis and Endometriosis: Should Mast Cells Be Targeted?

Hart

2015

International Journal of Inflammation

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“…However, several brain pathological conditions may be associated with an increased degranulation of mast cells in the choroid plexus , leading to a massive release of histamine in the CSF and the consequent increase of the blood brain barrier (BBB) permeability. Histaminergic neuronal activity (analyzed by positron emission tomography) was also found to be increased in the lesioned brain parenchyma (Vizuete et al, 2000 ; Motoki et al, 2005 ; Yanai and Tashiro, 2007 ; Kallweit et al, 2013 ). Importantly, histamine has been described to be involved in several brain pathologies such as seizures (Bhowmik et al, 2012 ), stroke (Fan et al, 2011 ), multiple sclerosis (Ballerini et al, 2013 ; Krementsov et al, 2013 ), Parkinson and Alzheimer's disease (Shan et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

“…Despite the absence of in vivo studies disclosing the role of histamine in the regulation of the SVZ neurogenic niche, in vitro studies have already shown that SVZ NSCs express functional H1R receptors that may be involved in neuronal commitment (Agasse et al, 2008 ; Bernardino et al, 2012 ). The relevance of investigating the effects of histamine on SVZ neurogenesis in vivo relies on the fact that both inflammation or brain injury may elicit choroid plexus mast cells degranulation, increasing the levels of histamine in the CSF and brain parenchyma leading to increased BBB permeability (Anichtchik et al, 2000 ; Yoshitake et al, 2003 ; Soya et al, 2008 ; Kanbayashi et al, 2009 ; Kallweit et al, 2013 ). The presence of histamine in the CSF that baths the SVZ neurogenic niche may affect SVZ GFAP-positive stem cells (type B cells) and its progeny in vivo by the direct contact of their cilia with the lumen of the lateral ventricles or by the interaction of stem/progenitor cells with the monolayer of ependymal cells (paracrine effect).…”

Section: Introductionmentioning

confidence: 99%

New insights into the role of histamine in subventricular zone-olfactory bulb neurogenesis

et al. 2014

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The subventricular zone (SVZ) contains neural stem cells (NSCs) that generate new neurons throughout life. Many brain diseases stimulate NSCs proliferation, neuronal differentiation and homing of these newborns cells into damaged regions. However, complete cell replacement has never been fully achieved. Hence, the identification of proneurogenic factors crucial for stem cell-based therapies will have an impact in brain repair. Histamine, a neurotransmitter and immune mediator, has been recently described to modulate proliferation and commitment of NSCs. Histamine levels are increased in the brain parenchyma and at the cerebrospinal fluid (CSF) upon inflammation and brain injury, thus being able to modulate neurogenesis. Herein, we add new data showing that in vivo administration of histamine in the lateral ventricles has a potent proneurogenic effect, increasing the production of new neuroblasts in the SVZ that ultimately reach the olfactory bulb (OB). This report emphasizes the multidimensional effects of histamine in the modulation of NSCs dynamics and sheds light into the promising therapeutic role of histamine for brain regenerative medicine.

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“…Histamine, one of the metabolites in histidine metabolism, has been shown to play regulatory role in EAE by altering the permeability of the BBB and promoting CNS inflammation [69,70]. Its levels were reported to be significantly higher in CSF of MS patients [71]. Changes in histidine metabolism could potentially affect histamine levels.The biosynthesis of histidine is inherently linked to the nucleotide pathway through 5-phosphoribosyl-1-pyrophsophate (PRPP) [72].…”

Section: Resultsmentioning

confidence: 99%

Profile of Circulatory Metabolites in an Animal Model of Multiple Sclerosis using Global Metabolomics

Nemutlu³

et al. 2013

J Clin Cell Immunol

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Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the CNS. Although, MS is well characterized in terms of the role played by immune cells, cytokines and CNS pathology, nothing is known about the metabolic alterations that occur during the disease process in circulation. Recently, metabolic aberrations have been defined in various disease processes either as contributing to the disease, as potential biomarkers, or as therapeutic targets. Thus in an attempt to define the metabolic alterations that may be associated with MS disease progression, we profiled the plasma metabolites at the chronic phase of disease utilizing relapsing remitting-experimental autoimmune encephalomyelitis (RR-EAE) model in SJL mice. At the chronic phase of the disease (day 45), untargeted global metabolomic profiling of plasma collected from EAE diseased SJL and healthy mice was performed, using a combination of high-throughput liquid-and-gas chromatography with mass spectrometry. A total of 282 metabolites were identified, with significant changes observed in 44 metabolites (32 up-regulated and 12 down-regulated), that mapped to lipid, amino acid, nucleotide and xenobiotic metabolism and distinguished EAE from healthy group (p<0.05, false discovery rate (FDR)<0.23). Mapping the differential metabolite signature to their respective biochemical pathways using the Kyoto Encyclopedia of Genes and Genomics (KEGG) database, we found six major pathways that were significantly altered (containing concerted alterations) or impacted (containing alteration in key junctions). These included bile acid biosynthesis, taurine metabolism, tryptophan and histidine metabolism, linoleic acid and D-arginine metabolism pathways. Overall, this study identified a 44 metabolite signature drawn from various metabolic pathways which correlated well with severity of the EAE disease, suggesting that these metabolic changes could be exploited as (1) biomarkers for EAE/MS progression and (2) to design new treatment paradigms where metabolic interventions could be combined with present and experimental therapeutics to achieve better treatment of MS.

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Elevated CSF histamine levels in multiple sclerosis patients

Cited by 26 publications

References 15 publications

Curbing Inflammation in Multiple Sclerosis and Endometriosis: Should Mast Cells Be Targeted?

Curbing Inflammation in Multiple Sclerosis and Endometriosis: Should Mast Cells Be Targeted?

New insights into the role of histamine in subventricular zone-olfactory bulb neurogenesis

Profile of Circulatory Metabolites in an Animal Model of Multiple Sclerosis using Global Metabolomics

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