scholarly journals Intracerebral Pro-inflammatory Cytokine Increase in Surgically Evacuated Intracerebral Hemorrhage - an Observational Microdialysis Study

2021 ◽  
Author(s):  
Lovisa Tobieson ◽  
Anna Gard ◽  
Karsten Ruscher ◽  
Niklas Marklund
Keyword(s):  
Intracerebral Hemorrhage ◽  
Brain Tissue ◽  
Inflammatory Cytokines ◽  
Inflammatory Mediators ◽  
Inflammatory Cytokine ◽  
Tissue Injury ◽  
Treatment Options ◽  
Cerebral Microdialysis ◽  
Cytokines And Chemokines ◽  
Anti Inflammatory

Abstract Background: Treatment options for spontaneous intracerebral hemorrhage (ICH) are limited. A possible inflammatory response in the brain tissue surrounding an ICH may exacerbate the initial injury and could be a target for treatment. Methods: In this observational study, ten patients needing surgical evacuation of supratentorial ICH received two cerebral microdialysis (MD) catheters; one in the perihemorrhagic zone (PHZ), and one in non-eloquent cortex (SNX) remote from the ICH. The microdialysate was analysed for energy metabolites (including lactate/pyruvate ratio (LPR) and glucose) and for inflammatory mediators using a multiplex immunoassay of 27 cytokines and chemokines at 6-10 hours, 20-26 hours and 44-50 hours after surgery. Results: Deranged energy metabolic markers suggestive of a metabolic crisis were found in PHZ compared to SNX, persistent throughout the 50 hours. Pro-inflammatory cytokines IL-8, TNF-α, IL-2, IL-1β, IL-6 and IFN-γ, anti-inflammatory cytokine IL-13, IL-4, and VEGF-A were significantly higher in PHZ compared to SNX, most prominent at 20-26 hours following ICH evacuation.Conclusions: Higher levels of pro- and anti-inflammatory cytokines in the perihemorrhagic brain tissue suggests a role for inflammatory mediators involved in secondary injury cascades potentially exacerbating tissue injury, which may constitute a target for future medical interventions.

scholarly journals Intracerebral Proinflammatory Cytokine Increase in Surgically Evacuated Intracerebral Hemorrhage: A Microdialysis Study

2021 ◽  
Author(s):  
Lovisa Tobieson ◽  
Anna Gard ◽  
Karsten Ruscher ◽  
Niklas Marklund
Keyword(s):  
Intracerebral Hemorrhage ◽  
Brain Tissue ◽  
Inflammatory Mediators ◽  
Treatment Options ◽  
Interferon Γ ◽  
Cerebral Microdialysis ◽  
Secondary Brain Injury ◽  
Study Objective ◽  
Surgical Evacuation ◽  
Anti Inflammatory

Abstract Background Treatment options for spontaneous intracerebral hemorrhage (ICH) are limited. A possible inflammatory response in the brain tissue surrounding an ICH may exacerbate the initial injury and could be a target for treatment of subsequent secondary brain injury. The study objective was to compare levels of inflammatory mediators in the interstitial fluid of the perihemorrhagic zone (PHZ) and in seemingly normal cortex (SNX) in the acute phase after surgical evacuation of ICH, with the hypothesis being that a difference could be demonstrated between the PHZ and the SNX. Methods In this observational study, ten patients needing surgical evacuation of supratentorial ICH received two cerebral microdialysis catheters: one in the PHZ and one in the SNX that is remote from the ICH. The microdialysate was analyzed for energy metabolites (including lactate pyruvate ratio and glucose) and for inflammatory mediators by using a multiplex immunoassay of 27 cytokines and chemokines at 6–10 h, 20–26 h, and 44–50 h after surgery. Results A metabolic crisis, indicated by altered energy metabolic markers, that persisted throughout the observation period was observed in the PHZ when compared with the SNX. Proinflammatory cytokines interleukin (IL) 8, tumor necrosis factor α, IL-2, IL-1β, IL-6 and interferon γ, anti-inflammatory cytokine IL-13, IL-4, and vascular endothelial growth factor A were significantly higher in PHZ compared with SNX and were most prominent at 20–26 h following ICH evacuation. Conclusions Higher levels of both proinflammatory and anti-inflammatory cytokines in the perihemorrhagic brain tissue implies a complex role for inflammatory mediators in the secondary injury cascades following ICH surgery, suggesting a need for targeted pharmacological interventions.

scholarly journals Pro- and Anti-Inflammatory Cytokines Release in Mice Injected withCrotalus durissus terrificusVenom

2008 ◽  
Vol 2008 ◽  
pp. 1-10 ◽  
Author(s):  
A. Hernández Cruz ◽  
S. Garcia-Jimenez ◽  
R. Zucatelli Mendonça ◽  
V. L. Petricevich
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Mediators ◽  
Inflammatory Cytokine ◽  
Time Course ◽  
Dependent Manner ◽  
Blood Biochemical ◽  
Cytokine Balance ◽  
Anti Inflammatory ◽  
Crotalus Durissus ◽  
Anti Inflammatory Cytokine

The effects ofCrotalus durissus terrificusvenom (Cdt) were analyzed with respect to the susceptibility and the inflammatory mediators in an experimental model of severe envenomation. BALB/c female mice injected intraperitoneally presented sensibility to Cdt, with changes in specific signs, blood biochemical and inflammatory mediators. The venom induced reduction of glucose and urea levels and an increment of creatinine levels in serum from mice. Significant differences were observed in the time-course of mediator levels in sera from mice injected with Cdt. The maximum levels of IL-6, NO, IL-5, TNF, IL-4 and IL-10 were observed 15 min, 30 min, 1, 2 and 4 hours post-injection, respectively. No difference was observed for levels of IFN-γ. Taken together, these data indicate that the envenomation by Cdt is regulated both pro- and anti-inflammatory cytokine responses at time-dependent manner. In serum from mice injected with Cdt at the two first hours revealed of pro-inflammatory dominance. However, with an increment of time an increase of anti-inflammatory cytokines was observed and the balance toward to anti-inflammatory dominance. In conclusion, the observation that Cdt affects the production of pro- and anti-inflammatory cytokines provides further evidence for the role played by Cdt in modulating pro/anti-inflammatory cytokine balance.

scholarly journals Extracellular fluid, cerebrospinal fluid and plasma biomarkers of axonal and neuronal injury following intracerebral hemorrhage

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lovisa Tobieson ◽  
Henrik Zetterberg ◽  
Kaj Blennow ◽  
Niklas Marklund
Keyword(s):  
Cerebrospinal Fluid ◽  
Intracerebral Hemorrhage ◽  
Brain Tissue ◽  
Single Molecule ◽  
Tissue Injury ◽  
Extracellular Fluid ◽  
Neurofilament Light ◽  
Aβ Peptides ◽  
Post Surgery ◽  
Fluid Compartments

AbstractSpontaneous intracerebral hemorrhage (ICH) is the most devastating form of stroke. To refine treatments, improved understanding of the secondary injury processes is needed. We compared energy metabolic, amyloid and neuroaxonal injury biomarkers in extracellular fluid (ECF) from the perihemorrhagic zone (PHZ) and non-injured (NCX) brain tissue, cerebrospinal fluid (CSF) and plasma. Patients (n = 11; age 61 ± 10 years) undergoing ICH surgery received two microdialysis (MD) catheters, one in PHZ, and one in NCX. ECF was analysed at three time intervals within the first 60 h post- surgery, as were CSF and plasma samples. Amyloid-beta (Aβ) 40 and 42, microtubule associated protein tau (tau), and neurofilament-light (NF-L) were analysed using Single molecule array (Simoa) technology. Median biomarker concentrations were lowest in plasma, higher in ECF and highest in CSF. Biomarker levels varied over time, with different dynamics in the three fluid compartments. In the PHZ, ECF levels of Aβ40 were lower, and tau higher when compared to the NCX. Altered levels of Aβ peptides, NF-L and tau may reflect brain tissue injury following ICH surgery. However, the dynamics of biomarker levels in the different fluid compartments should be considered in the study of pathophysiology or biomarkers in ICH patients.

scholarly journals Microglial phenotypes in the human epileptic temporal lobe

Brain ◽  
2018 ◽  
Vol 141 (12) ◽  
pp. 3343-3360 ◽  
Author(s):  
Mélanie Morin-Brureau ◽  
Giampaolo Milior ◽  
Juliette Royer ◽  
Farah Chali ◽  
Caroline Le Duigou ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Temporal Lobe ◽  
Inflammatory Cytokine ◽  
Anatomical Studies ◽  
Microglial Phenotype ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine

Using transcriptomics, anatomical studies, imaging and ELISA, Morin-Brureau et al. examine microglia in patients with temporal lobe epilepsies. In highly sclerotic regions such as CA1, the anti-inflammatory cytokine IL-10 regulates microglial phenotype. Seizures induce a transient microglial phenotype associated with secretion of inflammatory cytokines including human CXCL8.

scholarly journals Differential Cytokine-Induced Responses of Polarized Microglia

2021 ◽  
Vol 11 (11) ◽  
pp. 1482
Author(s):  
Priyanka Chauhan ◽  
Wen S. Sheng ◽  
Shuxian Hu ◽  
Sujata Prasad ◽  
James R. Lokensgard
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Mediators ◽  
Cell Polarization ◽  
Microglial Cells ◽  
Color Flow ◽  
Arginase 1 ◽  
Activated State ◽  
Ifn Γ ◽  
Anti Inflammatory ◽  
Differential Responses

The role of select pro- and anti-inflammatory mediators in driving microglial cell polarization into classically (M1), or alternatively, (M2) activated states, as well as the subsequent differential responses of these induced phenotypes, was examined. Expression of PD-L1, MHC-II, MHC-I, arginase 1 (Arg-1), and inducible nitric oxide synthase (iNOS) was assessed using multi-color flow cytometry. We observed that both pro- and anti-inflammatory mediators induced PD-L1 expression on non-polarized microglia. Moreover, IFN-γ stimulated significant MHC class I and II expression on these cells. Interestingly, we observed that only IL-4 treatment induced Arg-1 expression, indicating M2 polarization. These M2 cells were refractory to subsequent depolarization and maintained their alternatively activated state. Furthermore, PD-L1 expression was significantly induced on these M2-polarized microglia after treatment with pro-inflammatory mediators, but not anti-inflammatory cytokines. In addition, we observed that only LPS induced iNOS expression in microglial cells, indicating M1 polarization. Furthermore, IFN-γ significantly increased the percentage of M1-polarized microglia expressing iNOS. Surprisingly, when these M1-polarized microglia were treated with either IL-6 or other anti-inflammatory cytokines, they returned to their non-polarized state, as demonstrated by significantly reduced expression of iNOS. Taken together, these results demonstrate differential responses of microglial cells to mediators present in dissimilar microenvironments.

scholarly journals Leukocyte dynamics after intracerebral hemorrhage in a living patient reveal rapid adaptations to tissue milieu

2020 ◽  
Author(s):  
Brittany A. Goods ◽  
Michael H. Askenase ◽  
Erica Markarian ◽  
Hannah E. Beatty ◽  
Riley Drake ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Single Cell ◽  
Brain Tissue ◽  
Cellular Response ◽  
Tissue Injury ◽  
Brain Inflammation ◽  
Therapeutic Interventions ◽  
Acute Injury ◽  
The Brain ◽  
Over Time

ABSTRACTIntracerebral hemorrhage (ICH) is a devastating form of stroke with a high mortality rate and few treatment options. Discovery of therapeutic interventions has been slow given the challenges associated with studying acute injury, particularly over time, in the human brain. Inflammation induced by exposure of brain tissue to blood appears to be a major part of brain tissue injury. Here we longitudinally profiled blood and cerebral hematoma effluent from a patient enrolled in the Minimally Invasive Surgery with Thrombolysis in Intracerebral Haemorrhage Evacuation (MISTIEIII) trial, offering a rare window into the local and systemic immune responses to acute brain injury. Using single-cell RNA-sequencing, we characterized the local cellular response during ICH in the brain of a living patient at single-cell resolution for the first time. Our analysis revealed rapid shifts in the activation states of myeloid and T cells in the brain over time, suggesting that leukocyte responses are dynamically reshaped by the hematoma microenvironment. Interestingly, the patient had an asymptomatic re-bleed (second local exposure to blood) that our transcriptional data indicated occurred more than 30 hours prior to detection by CT scan. This case highlights the rapid immune dynamics in the brain after ICH and suggests that sensitive methods like scRNA-seq can inform our understanding of complex intracerebral events.

Anti-Inflammatory Effect of Lycii radicis in LPS-Stimulated RAW 264.7 Macrophages

2014 ◽  
Vol 42 (04) ◽  
pp. 891-904 ◽  
Author(s):  
Mi Young Song ◽  
Hyo Won Jung ◽  
Seok Yong Kang ◽  
Kyung-Ho Kim ◽  
Yong-Ki Park
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Mediators ◽  
Water Extract ◽  
Inhibitory Effect ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Root Bark ◽  
Lycium Barbarum ◽  
Anti Inflammatory ◽  
Inflammatory Effect

The root bark of Lycium barbarum (Lycii radicis cortex, LRC) is used as a cooling agent for fever and night sweats in East Asian traditional medicine. The inhibitory effect of LRC water extract on inflammation is unknown. In this study, the anti-inflammatory effect of LRC was investigated in lipopolysaccharide (LPS)-stimulated mouse macrophage, RAW 264.7 cells. LRC extract significantly decreased the LPS-induced production of inflammatory mediators, nitric oxide (NO), prostaglandin (PG) E2 and pro-inflammatory cytokines, interleukin (IL)-1β and IL-6 in the cells. In addition, LRC extract inhibited the LPS-induced expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 mRNA and protein, and inflammatory cytokines mRNA in the cells. The action mechanism of LRC underlies the blocking of LPS-mediated p38 and Jun N-terminal kinase (JNK), mitogen-activated protein kinases (MAPKs), and the nuclear factor (NF)-κB signaling pathway. These results indicate that LRC extract inhibits the inflammatory response in activated macrophages by down-regulating the transcription levels of inflammatory mediators and blocking the MAPKs and NF-κB pathway.

scholarly journals P0527AROLE OF PROMOTING INFLAMMATION OF KLF6 IN ACUTE KIDNEY INURY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Dan Li ◽  
Chenyu Li ◽  
Yan Xu
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Tnf Α ◽  
Public Dataset ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine ◽  
Pro Inflammatory Cytokines

Abstract Background and Aims Acute kidney injury (AKI), commonly appeared in cardiac arrest, surgery and kidney transplantation which involved in ischemia-reperfusion (IR) injury of kidney. However, the mechanisms underlying inflammatory response in IR AKI is still unclear. Method Public dataset showed kruppel-like factor 6 (KLF6) was significantly highly expressed (P<0.05) in AKI, implies KLF6 might be associated with AKI. To evaluate the mechanism of KLF6 on IR AKI, 30 rats were randomly divided into sham and IR group, and were sacrificed at 0 h, 3 h, 6 h, 12 h or 24 h after IR. Results The results showed KLF6 expression was peaking at 6 h after IR, and the expression of pro-inflammatory cytokines MCP-1 and TNF-α were increased both in serum and kidney tissues after IR, while anti-inflammatory cytokine IL-10 was decreased after IR. Furthermore, in vitro results showed KLF6 knock-down reduced the pro-inflammatory cytokines expression and increased the anti-inflammatory cytokines expression. Conclusion These results suggest that (1) KLF6 might be a novel biomarker for early diagnosis of AKI and (2) targeting KLF6 expression may offer novel strategies to protect kidneys from IR AKI Figure KLF6, AKI, Control Inflammation

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