Chemokines after human ischemic stroke: From neurovascular unit to blood using protein arrays

García‐Berrocoso, Teresa; Giralt, Dolors; Llombart, Víctor; Bustamante, Alejandro; Peñalba, Anna; Flores, Alan; Ribó, Marc; Molina, Carlos A.; Rosell, Anna; Montaner, Joan

doi:10.1016/j.trprot.2014.03.001

Cited by 20 publications

(21 citation statements)

References 72 publications

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“…Previous studies assessing the changes in the protein expression profile after human cerebral ischemia were based on MS analysis of the whole cerebral tissue (14,15) or explored the expression of targeted molecules in specific isolated cell types (18,19,28). The study being presented here explored, for the first time, the proteome of neurons and BBB structures isolated by LMD from human brains after stroke following a hypothesis-free analysis based on label-free MS.…”

Section: Discussionmentioning

confidence: 99%

“…However, when tissue homogenates are analyzed only global changes in the protein expression profile can be identified and the alterations in protein expression at a particular cellular level are not considered. Following a cell isolation approach based on laser microdissection (LMD), our group previously described ischemia-related changes in matrix metalloproteinase (18) and in chemokine (19) expression profiles in neurons and vascular cells dissected from human brain parenchyma.…”

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confidence: 99%

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Single Cell Immuno-Laser Microdissection Coupled to Label-Free Proteomics to Reveal the Proteotypes of Human Brain Cells After Ischemia

García‐Berrocoso

Llombart

Colàs-Campàs

et al. 2018

Molecular & Cellular Proteomics

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Cerebral ischemia entails rapid tissue damage in the affected brain area causing devastating neurological dysfunction. How each component of the neurovascular unit contributes or responds to the ischemic insult in the context of the human brain has not been solved yet. Thus, the analysis of the proteome is a straightforward approach to unraveling these cell proteotypes. In this study, post-mortem brain slices from ischemic stroke patients were obtained corresponding to infarcted (IC) and contralateral (CL) areas. By means of laser microdissection, neurons and blood brain barrier structures (BBB) were isolated and analyzed using label-free quantification. MS data are available via ProteomeXchange with identifier PXD003519. Ninety proteins were identified only in neurons, 260 proteins only in the BBB and 261 proteins in both cell types. Bioinformatics analyses revealed that repair processes, mainly related to synaptic plasticity, are outlined in microdissected neurons, with nonexclusive important functions found in the BBB. A total of 30 proteins showing < 0.05 and fold-change> 2 between IC and CL areas were considered meaningful in this study: 13 in neurons, 14 in the BBB and 3 in both cell types. Twelve of these proteins were selected as candidates and analyzed by immunohistofluorescence in independent brains. The MS findings were completely verified for neuronal SAHH2 and SRSF1 whereas the presence in both cell types of GABT and EAA2 was only validated in neurons. In addition, SAHH2 showed its potential as a prognostic biomarker of neurological improvement when analyzed early in the plasma of ischemic stroke patients. Therefore, the quantitative proteomes of neurons and the BBB (or proteotypes) after human brain ischemia presented here contribute to increasing the knowledge regarding the molecular mechanisms of ischemic stroke pathology and highlight new proteins that might represent putative biomarkers of brain ischemia or therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Single Cell Immuno-Laser Microdissection Coupled to Label-Free Proteomics to Reveal the Proteotypes of Human Brain Cells After Ischemia

García‐Berrocoso

Llombart

Colàs-Campàs

et al. 2018

Molecular & Cellular Proteomics

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“…[100][101][102] In recent years, more attention has been paid to these markers, confirming their significant contribution to the occurrence of cerebral ischemic lesions. [103][104][105] Chemokines and their receptors act as both trophic and protective modules in the nervous system, thus increasing the survival of neurons. What is important, they not only regulate neuronal metabolism, but also affect their synaptic transmission.…”

Section: Selected Chemokines In Strokesmentioning

confidence: 99%

“…Their contribution has been found in, eg, cardiovascular diseases, strokes and many inflammatory and autoimmune diseases, as well as in brain damage. 103,[109][110][111][112][113][114] Increased expressions of chemokine genes in the brain can be caused not only by ischemia, but also by, eg, axonal damage or neurotoxins. 115 Although the contribution of chemokines to the pathogenesis of stroke has been demonstrated in both animal and human models, this issue still remains controversial.…”

Section: Selected Chemokines In Strokesmentioning

confidence: 99%

<p>The Role of Selected Pro-Inflammatory Cytokines in Pathogenesis of Ischemic Stroke</p>

Pawluk¹,

Woźniak²,

Grześk³

et al. 2020

CIA

116

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Stroke is currently one of the most common causes of death and disability in the world, and its pathophysiology is a complex process, involving the oxidative stress and inflammatory reaction. Unfortunately, no biochemical factors useful in the diagnostics and treatment of stroke have been clearly established to date. Therefore, researchers are increasingly interested in the inflammatory response triggered by cerebral ischemia and its role in the development of cerebral infarction. This article gives an overview of the available literature data concerning the role of pro-inflammatory cytokines in acute stroke. Detailed analysis of their role in cerebral circulation disturbances can also suggest certain immune response regulatory mechanisms aimed to reduce damage to the nervous tissue in the course of stroke.

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“…In one study, chemokines CCL17 and CCL22 showed a very faint power to discriminate patients who improve within the fi rst 24-48 h after stroke from the remaining. Indeed, none of these chemokines seems to be a reliable prognostic biomarker in the hyperacute phase of stroke [ 61 ].…”

Section: Infl Ammatory Biomarkersmentioning

confidence: 99%

Ischemic Stroke

Fonseca¹,

Sousa²,

Ferro³

2015

Biomarkers of Cardiometabolic Risk, Inflammation and Disease

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In recent years, there was a surge in interest for biomarkers in ischemic stroke, with several purposes. In this chapter we will focus on biomarkers with potential use in ischemic stroke, namely, in diagnosis, grading of severity, identification of subtypes, and prediction of outcome or recurrence. A special emphasis will be placed on the role of infl ammation in stroke, as it plays a key role in the cascade of events leading to progression of ischemic brain injury. However, the role of biomarkers in the clinical management of ischemic stroke is still limited. Therapeutic trials attempting to intervene on the infl ammatory process are also briefl y mentioned.

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Chemokines after human ischemic stroke: From neurovascular unit to blood using protein arrays

Cited by 20 publications

References 72 publications

Single Cell Immuno-Laser Microdissection Coupled to Label-Free Proteomics to Reveal the Proteotypes of Human Brain Cells After Ischemia

Single Cell Immuno-Laser Microdissection Coupled to Label-Free Proteomics to Reveal the Proteotypes of Human Brain Cells After Ischemia

<p>The Role of Selected Pro-Inflammatory Cytokines in Pathogenesis of Ischemic Stroke</p>

Ischemic Stroke

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