Mast cells in the human brain

Dropp, John J.

doi:10.1159/000145157

Cited by 58 publications

(32 citation statements)

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“…Mast cells are present in the brain, including the neopallium, where their numbers increase during early postnatal development (13)(14)(15)(16)(17). Mast cells are derived from the pluripotent hematopoietic stem cells in the bone marrow.…”

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confidence: 99%

Deleterious Effects of IL-9–Activated Mast Cells and Neuroprotection by Antihistamine Drugs in the Developing Mouse Brain

et al. 2001

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Elevated mean IL-9 serum levels have been observed in human neonates who will later develop cerebral palsy. In earlier studies, using a newborn mouse model of excitotoxic lesions mimicking those described in human cerebral palsy, we found that IL-9 pretreatment exacerbated brain damage produced by intracerebral injections of the glutamatergic analog ibotenate. Among its different cell targets, the Th2 cytokine IL-9 is a mast cell growth and differentiation factor that can cause mast cells to release various substances including histamine. In the present study, we sought to determine whether the deleterious effects of IL-9 in our mouse model were mediated by mast cells through histamine release. All mouse pups were pretreated with intraperitoneal injections of IL-9 or saline between postnatal days (P) P1 and P5. Immunohistochemistry for murine mast cell protease-1 performed on P5 showed an increased density of labeled cells in the neopallium of IL-9 -treated Swiss pups as compared with controls. Western blot analysis confirmed the increased murine mast cell protease-1 brain content of IL-9 -treated Swiss mice. IL-9 pretreatment had no significant effect on ibotenateinduced excitotoxic brain lesions in mast cell-deficient P5 pups (WBB6F1/J kit W/W-v ), whereas IL-9 exacerbated these lesions in the control littermates with normal mast cell populations. Finally, cromoglycate or antihistamine drugs significantly reduced ibotenate-induced brain lesions in IL-9 -treated Swiss pups. Taken together, these data suggest that recruitment of cerebral mast cells with histamine release may contribute to the exacerbation of neonatal excitotoxic brain lesions produced by IL-9. Neuroprotective strategies targeting mast cells may be useful in some neonates at risk for cerebral palsy. (1-7). Recent hypotheses have implicated multiple preconceptional and prenatal factors, such as hypoxiaperfusion failure, genetic factors, growth factor deficiency, and excess production of cytokines. In a striking retrospective study, mean levels of perinatal circulating cytokines-including IL-1␤, IL-6, IL-8, IL-9, and TNF-␣-were higher in patients with subsequent occurrence of cerebral palsy than in control subjects (8).In that study, although the numbers of included patients were limited, levels of proinflammatory cytokines (IL-1-␤, IL-6, IL-8, and TNF-␣) were associated with one another, but no correlation was detected between IL-9 levels and the levels of the other cytokines tested. Although further studies will be necessary to confirm this initial observation, these data could suggest the existence of a subpopulation of cerebral palsy patients characterized by increased levels of circulating IL-9 at birth. A better understanding of the mechanisms bridging IL-9 blood level elevation and brain damage might open up new therapeutic possibilities for preventing cerebral palsy in infants with high circulating IL-9 levels.Intracerebral injection of ibotenate, a glutamate analog, to newborn mice produces histologic lesions mimicking the brain lesions f...

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Deleterious Effects of IL-9–Activated Mast Cells and Neuroprotection by Antihistamine Drugs in the Developing Mouse Brain

et al. 2001

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“…Mastocytic activation Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/brainres occurs upon response to a wide range of physical and chemical stimuli, including trauma, hypoxia, allergens, toxic substances, complement factors, endogenous and exogenous peptides, cytokines and other inflammatory mediators (Galli et al, 2005). MCs also are present in the central nervous system (CNS) and they have been identified in different mammalian brain regions, including meninges, choroid plexus, olfactory bulb, mesencephalon, parenchima of thalamus and hypothalamus, hippocampus and enthorinal cortex (Dropp, 1979;Silver and Curley, 2013;Theoharides, 1990). MCs have been associated with various neuroinflammatory conditions of the CNS, such as stroke, multiple sclerosis, traumatic brain injury and eventually Alzheimer's Disease (AD) and Parkinson's Disease (PD) (Nelissen et al, 2013).…”

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confidence: 99%

PEA and luteolin synergistically reduce mast cell-mediated toxicity and elicit neuroprotection in cell-based models of brain ischemia

et al. 2016

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a b s t r a c tThe combination of palmitoylethanolamide (PEA), an endogenous fatty acid amide belonging to the family of the N-acylethanolamines, and the flavonoid luteolin has been found to exert neuroprotective activities in a variety of mouse models of neurological disorders, including brain ischemia. Indirect findings suggest that the two molecules can reduce the activation of mastocytes in brain ischemia, thus modulating crucial cells that trigger the inflammatory cascade. Though, no evidence exists about a direct effect of PEA and luteolin on mast cells in experimental models of brain ischemia, either used separately or in combination. In order to fill this gap, we developed a novel cell-based model of severe brain ischemia consisting of primary mouse cortical neurons and cloned mast cells derived from mouse fetal liver (MC/9 cells) subjected to oxygen and glucose deprivation (OGD).OGD exposure promoted both mast cell degranulation and the release of lactate dehydrogenase (LDH) in a time-dependent fashion. MC/9 cells exacerbated neuronal damage in neuron-mast cells co-cultures exposed to OGD. Likewise, the conditioned medium derived from OGD-exposed MC/9 cells induced significant neurotoxicity in control primary neurons. PEA and luteolin pre-treatment synergistically prevented the OGD-induced degranulation of mast cells and reduced the neurotoxic potential of MC/9 cells conditioned medium. Finally, the association of the two drugs promoted a direct synergistic neuroprotection even in pure cortical neurons exposed to OGD.In summary, our results indicate that mast cells release neurotoxic factors upon OGD-induced activation. The association PEA-luteolin actively reduces mast cell-mediated neurotoxicity as well as pure neurons susceptibility to OGD.

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The numbers of mast cells in the plaque border zones of females is twice as high as in males [3].

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Are Mast Cells the Key to Multiple Sclerosis?

Krüger¹

2015

J Mult Scler (Foster City)

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Mast cells are not present in the normal and unaffected human brain [1], but were observed in the brains of MS patient 1890 [2]. From recent observations, it seems that all symptoms we recognize in MS may be explained by the presence of these cells.The numbers of mast cells in the plaque border zones of females is twice as high as in males [3]. This fact may explain why MS is more abundant in females than men [4].Stimulated mast cells secrete histamine, and histamine evokes oedema formation which is frequently registered in MS.Stimulated mast cells even secrete proteases. Mast cell proteases dissolves myelin [5], and demyelination is of course the most serious and MS-defining effect of the mast cells. A strong association between mast cells and MS is further strengthened by the fact that elevated mast cell tryptase is observed in the cerebrospinal fluid of MS patients [6], as well as the observation that mast cell transcripts are increased within and outside multiple sclerosis lesions [7].Mast cells recover after depletion of their granular contents (e.g., histamine and protease) [8] which may explain the relapsing remitting periods that often characterize the disease; Massive stimulation of the mast cells: (relapsing), and then the silent period (remitting) when the cells recover and build up capacity for another relapse.The theory that mast cells influence the development of MS is fascinating close and simple to follow, and all the more should, at least from a theoretical point of view, be easy to challenge since we have mast cell blockers, and also antihistamines that may block the histamine opening up of BB-barrier, and thus hopefully stop secretagoques, what ever they are, to stimulate the perivascular mast cells.

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Mast cells in the human brain

Cited by 58 publications

References 10 publications

Deleterious Effects of IL-9–Activated Mast Cells and Neuroprotection by Antihistamine Drugs in the Developing Mouse Brain

Deleterious Effects of IL-9–Activated Mast Cells and Neuroprotection by Antihistamine Drugs in the Developing Mouse Brain

PEA and luteolin synergistically reduce mast cell-mediated toxicity and elicit neuroprotection in cell-based models of brain ischemia

Are Mast Cells the Key to Multiple Sclerosis?

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