Mast Cells Promote Blood Brain Barrier Breakdown and Neutrophil Infiltration in a Mouse Model of Focal Cerebral Ischemia

McKittrick, Craig Martin; Lawrence, Catherine E.; Carswell, Hilary V O

doi:10.1038/jcbfm.2014.239

Cited by 71 publications

(72 citation statements)

References 40 publications

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“…[11] During the first few hours, neutrophils penetrate into the hypoxemic tissue which is invaded by macrophages and monocytes on consecutive days. [12] These cells are known to produce cytokines, free radicals, metalloproteinases, nitric oxide and much more. Such substances directly harm the nerve tissue, induce apoptosis and damage the blood-brain barrier.…”

Section: Discussionmentioning

confidence: 99%

The importance of selected markers of inflammation and blood-brain barrier damage for short-term post-stroke prognosis

Lasek–Bal

Jędrzejowska–Szypułka

Student

et al. 2018

Preprint

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Acute cerebral ischemia triggers local and systemic immune response. The aims of this project was to assess the blood serum concentration of the markers of inflammation and markers of the blood brain barrier damage on the first day of ischemic stroke, and the mutual correlations between these marker levels. Methods Our prospective study included 138 patients with first-in-life stroke, who were analyzed according to: plasma concentration of the following markers on the first day of stroke: Il-2 and IL-6, S100B, TNF alfa, GRN, NSE, uPA, VEGF, BDNF, CRP, leucocyte and thrombocyte counts; their neurological status on the first day of stroke (NIHSS) and their functional status at 30 days following stroke (mRS). Result The study included 138 patients with mean age: 73.11 ± 11.48 [36-103]. Patients with a higher score on the NIHSS than those obtaining lower scores showed significantly higher concentrations of TNF-alpha, WBC, CRP, NSE, IL-6 and S100B. Patients with a higher score on the mRS than those obtaining lower scores showed significantly higher concentrations of WBC, CRP, GRN, IL-6, S100B. Factors with an independent influence on the neurological status on the first day of stroke were: sex, WBC, PLT, CRP, S100B and IL-6 levels. Atrial fibrillation, leukocyte count, CRP, NSA, uPA, interleukin 6 and S100B showed an independent impact on the functional status on the 30th day of stroke. Patients with symptomatic atherosclerosis of carotid/cerebral and/or coronary arteries, as compared to others, were older (p= 0.003) and had higher levels of CRP, Il-6, and S100B. In each case, the differences were statistically significant. Conclusions The concentration of Il-6 and S100B on the first day of stroke are significant for both the neurological status and the functional status in the acute period of the disease. Increased CRP and leukocyte count are associated with a worse prognosis regarding the course of acute stroke. The expression of pro-inflammatory agents and markers of blood-brain barrier damage in the acute phase of stroke is more prominent in patients with symptomatic atherosclerosis than in patients with no clinical features of atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

The importance of selected markers of inflammation and blood-brain barrier damage for short-term post-stroke prognosis

Lasek–Bal

Jędrzejowska–Szypułka

Student

et al. 2018

Preprint

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“…We further report that MPP + up-regulates the expression of CD40L in Wt BMMCs co-cultured with glia/neurons in an in vitro co-culture system. Mast cells play an important role in the mechanism of BBB dysfunction, neuroinflammation and frequently co-localized next to glial cells in neuroinflammatory conditions in the brain (Seeldrayers et al, 1992; Kim et al, 2010; McKittrick et al, 2015). Previous studies have shown that intravenously administered BMMCs as well as peripheral mast cells infiltrate the brain in pathological conditions and thus exacerbate neuroinflammatory response (Silverman et al, 2000; Tanzola et al, 2003; Bennett et al, 2009; Skaper et al, 2012; Skaper et al, 2013a).…”

Section: Discussionmentioning

confidence: 99%

Cross-Talk between Glia, Neurons and Mast Cells in Neuroinflammation Associated with Parkinson’s Disease

Kempuraj

Selvakumar

Zaheer

et al. 2017

J Neuroimmune Pharmacol

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Parkinson’s disease (PD) is a progressive movement disorder characterized by neuroinflammation and dopaminergic neurodegeneration in the brain. 1-methyl-4-phenylpyridinium (MPP+), a metabolite of the parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces the release of inflammatory mediators from glial cells and neurons. Glia maturation factor (GMF), a brain proinflammatory protein, MPP+, and mast cell-derived inflammatory mediators induce neurodegeneration which eventually leads to PD. However, the precise mechanisms underlying interaction between glial cells, neurons and mast cells in PD still remain elusive. In the present study, mouse bone marrow-derived mast cells (BMMCs) and mouse fetal brain-derived mixed glia/neurons, astrocytes and neurons were incubated with MPP+, GMF and mast cell-derived inflammatory mediators mouse mast cell protease-6 (MMCP-6), MMCP-7 or tryptase/brain-specific serine protease-4 (tryptase/BSSP-4). Inflammatory mediators released from these cells in the culture medium were quantitated by enzyme-linked immunosorbent assay. Neurodegeneration was quantified by measuring total neurite outgrowth following microtubule-associated protein-2 immunocytochemistry. MPP+− induced significant neurodegeneration with reduced total neurite outgrowth. MPP+− induced the release of tryptase/BSSP-4 from the mouse mast cells, and tryptase/BSSP-4 induced chemokine (C-C motif) ligand 2 (CCL2) release from astrocytes and glia/neurons. Overall our results suggest that MPP+, GMF, MMCP-6 or MMCP-7 stimulate glia/neurons, astrocytes or neurons to release CCL2 and matrix metalloproteinase-3. Additionally, CD40L expression is increased in BMMCs after incubation with MPP+ in a co-culture system consisting of BMMCs and glia/neurons. We propose that mast cell interaction with glial cells and neurons during neuroinflammation can be explored as a new therapeutic target for PD.

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“…Male animals, used to exclude potential estrous cycle effects (13), were group housed under standard conditions at 21°C on a 12:12-h light-dark cycle with environmental enrichment and ad libitum access to water and food. All efforts were made to minimize animal suffering, and the number of animals used, n ϭ 6 rats/group for the MCAO study and n ϭ 5-7 rats/group for the platelet study, was based on a priori power calculations at 80% power and a significance level of 5% (52) and on previous publications (30,43,54). In all experiments, terminal anesthesia was induced and maintained by inhalation of isoflurane.…”

Section: Animalsmentioning

confidence: 99%

Detrimental effects of 2-arachidonoylglycerol on whole blood platelet aggregation and on cerebral blood flow after a focal ischemic insult in rats

Shearer

Coker

Carswell

2018

American Journal of Physiology-Heart and Circulatory Physiology

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This version is available at https://strathprints.strath.ac.uk/62815/ Strathprints is designed to allow users to access the research output of the University of Strathclyde. Unless otherwise explicitly stated on the manuscript, Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Please check the manuscript for details of any other licences that may have been applied. You may not engage in further distribution of the material for any profitmaking activities or any commercial gain. You may freely distribute both the url (https://strathprints.strath.ac.uk/) and the content of this paper for research or private study, educational, or not-for-profit purposes without prior permission or charge.Any correspondence concerning this service should be sent to the Strathprints administrator: strathprints@strath.ac.ukThe Strathprints institutional repository (https://strathprints.strath.ac.uk) is a digital archive of University of Strathclyde research outputs. It has been developed to disseminate open access research outputs, expose data about those outputs, and enable the management and persistent access to Strathclyde's intellectual output. RESEARCH ARTICLE Integrative Cardiovascular Physiology and PathophysiologyDetrimental effects of 2-arachidonoylglycerol on whole blood platelet aggregation and on cerebral blood flow after a focal ischemic insult in rats Shearer JA, Coker SJ, Carswell HVO. Detrimental effects of 2-arachidonoylglycerol on whole blood platelet aggregation and on cerebral blood flow after a focal ischemic insult in rats. Am J Physiol Heart Circ Physiol 314: H967-H977, 2018. First published January 5, 2018; doi:10.1152/ajpheart.00299.2017.-2-Arachidonoylglycerol (2-AG) is a major modulator of blood flow and platelet aggregation and a potential neuroprotectant. The present study investigated, for the first time, the effects of 2-AG on cerebral blood flow (CBF) in the first critical hours during middle cerebral artery occlusion (MCAO) and on platelet aggregation in rats. Adult male Sprague-Dawley rats (n ϭ 30) underwent permanent MCAO under isoflurane anesthesia and were randomly assigned to receive either 2-AG (6 mg/kg iv), monoacylglycerol lipase inhibitor JZL-184 (10 mg/kg iv), or vehicle (n ϭ 6 rats/group) treatment. CBF and cardiovascular responses were measured, by a blinded investigator, for up to 4 h. In separate experiments, platelet aggregation by 2-AG (19 -300 M) was assessed by whole blood aggregometry (n ϭ 40). 2-AG and JZL-184 significantly increased the severity of the CBF deficit versus vehicle (20.2 Ϯ 8.8% and 22.7 Ϯ 6.4% vs. 56.4 Ϯ 12.1% of pre-MCAO baseline, respectively, P Ͻ 0.05) but had no effect on blood pressure or heart rate. While JZL-184 significantly increased the number of thrombi after MCAO, this did not reach significance by 2-AG. 2-AG induced platelet aggregation in rat whole blood in a similar manner to arachidonic acid and was significantly reduced by the cyclooxygenase inhibitors indomethacin and flurb...

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Mast Cells Promote Blood Brain Barrier Breakdown and Neutrophil Infiltration in a Mouse Model of Focal Cerebral Ischemia

Cited by 71 publications

References 40 publications

The importance of selected markers of inflammation and blood-brain barrier damage for short-term post-stroke prognosis

The importance of selected markers of inflammation and blood-brain barrier damage for short-term post-stroke prognosis

Cross-Talk between Glia, Neurons and Mast Cells in Neuroinflammation Associated with Parkinson’s Disease

Detrimental effects of 2-arachidonoylglycerol on whole blood platelet aggregation and on cerebral blood flow after a focal ischemic insult in rats

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