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 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 Natural feed contaminant zearalenone decreases the expressions of important pro- and anti-inflammatory mediators and mitogen-activated protein kinase/NF-κB signalling molecules in pigs

2013 ◽  
Vol 111 (3) ◽  
pp. 452-464 ◽  
Author(s):  
Gina Cecilia Pistol ◽  
Mihail Alexandru Gras ◽  
Daniela Eliza Marin ◽  
Florentina Israel-Roming ◽  
Mariana Stancu ◽  
...  
Keyword(s):  
Immune Response ◽  
Protein Kinase ◽  
Matrix Metalloproteinases ◽  
Inflammatory Mediators ◽  
Interferon Γ ◽  
Mitogen Activated Protein Kinase ◽  
Economic Point ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory

Zearalenone (ZEA) is an oestrogenic mycotoxin produced byFusariumspecies, considered to be a risk factor from both public health and agricultural perspectives. In the presentin vivostudy, a feeding trial was conducted to evaluate thein vivoeffect of a ZEA-contaminated diet on immune response in young pigs. The effect of ZEA on pro-inflammatory (TNF-α, IL-8, IL-6, IL-1β and interferon-γ) and anti-inflammatory (IL-10 and IL-4) cytokines and other molecules involved in inflammatory processes (matrix metalloproteinases (MMP)/tissue inhibitors of matrix metalloproteinases (TIMP), nuclear receptors: PPARγ and NF-κB1, mitogen-activated protein kinases (MAPK): mitogen-activated protein kinase kinase kinase 7 (TAK1)/mitogen-activated protein kinase 14 (p38α)/mitogen-activated protein kinase 8 (JNK1)/ mitogen-activated protein kinase 9 (JNK2)) in the liver of piglets was investigated. The present results showed that a concentration of 316 parts per billion ZEA leads to a significant decrease in the levels of pro- and anti-inflammatory cytokines at both gene expression and protein levels, correlated with a decrease in the levels of other inflammatory mediators, MMP and TIMP. The results also showed that dietary ZEA induces a dramatic reduction in the expressions ofNF-κB1andTAK1/p38αMAPK genes in the liver of the experimentally intoxicated piglets, and has no effect on the expression ofPPARγmRNA. The present results suggest that the toxic action of ZEA begins in the upstream of the MAPK signalling pathway by the inhibition of TAK1, a MAPK/NF-κB activator. In conclusion, the present study shows that ZEA alters several important parameters of the hepatic cellular immune response. From an economic point of view, these data suggest that, in pigs, ZEA is not only a powerful oestrogenic mycotoxin but also a potential hepatotoxin when administered through the oral route. Therefore, the present results represent additional data from cellular and molecular levels that could be taken into account in the determination of the regulation limit of the tolerance to ZEA.

scholarly journals A proteomic investigation of protein adsorption to cerebral microdialysis membranes in surgically treated intracerebral hemorrhage patients

2020 ◽  
Author(s):  
Lovisa Tobieson ◽  
Zita Czifra ◽  
Karin Wåhlén ◽  
Niklas Marklund ◽  
Bijar Ghafouri
Keyword(s):  
Intracerebral Hemorrhage ◽  
Human Brain ◽  
Protein Adsorption ◽  
Brain Tissue ◽  
Cerebral Microdialysis ◽  
Invasive Technique ◽  
Human Brain Tissue ◽  
Protein Patterns ◽  
Molecular Weight Range ◽  
Two Dimensional Gel Electrophoresis

Abstract Background: Cerebral microdialysis (CMD) is a minimally invasive technique for sampling the interstitial fluid in human brain tissue. CMD allows monitoring the metabolic state of tissue, as well as sampling macromolecules such as proteins and peptides. Recovery of proteins or peptides can be hampered by their adsorption to the CMD membrane as has been previously shown in-vitro, however, protein adsorption to CMD membranes has not been characterized following implantation in human brain tissue. Methods: In this paper, we describe the pattern of proteins adsorbed to CMD membranes compared to that of the microdialysate and of cerebrospinal fluid (CSF). We retrieved CMD membranes from three surgically treated intracerebral hemorrhage (ICH) patients, and analyzed protein adsorption to the membranes using two-dimensional gel electrophoresis (2-DE) in combination with nano-liquid mass spectrometry. We compared the proteome profile of three compartments; the CMD membrane, the microdialysate and ventricular CSF collected at time of CMD removal. Results: We found unique protein patterns for each of the three compartments, particularly in the molecular weight range of 10–35 kDa. Conclusion: This study highlights the importance of analyzing the membranes in addition to the microdialysate when using CMD to sample proteins for biomarker investigation.

Brain edema after intracerebral hemorrhage: mechanisms, treatment options, management strategies, and operative indications

2007 ◽  
Vol 22 (5) ◽  
pp. 1-7 ◽  
Author(s):  
Ruth Thiex ◽  
Stella E. Tsirka
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Brain Edema ◽  
Treatment Options ◽  
Management Strategies ◽  
Convincing Evidence ◽  
Secondary Brain Injury ◽  
Edema Formation ◽  
Clot Removal ◽  
Operative Indications

✓Primary intracerebral hemorrhage (ICH) is associated with a high mortality rate and severe morbidity. The treatment of choice is still controversial, given that data from several clinical trials have not provided convincing evidence to support the efficacy of surgical clot removal. Favoring early clot removal is evidence that the limited release of specific neurotoxins associated with the breakdown products of hemoglobin underlies secondary brain injury. Attention has therefore shifted to perilesional brain injury, especially brain edema, as a potential target for therapeutic intervention in patients with ICH. In this review the authors address current understanding of the causes of edema formation following ICH and the treatment options, which are mostly supportive in nature.

scholarly journals A proteomic investigation of protein adsorption to cerebral microdialysis membranes in surgically treated intracerebral hemorrhage patients

2020 ◽  
Author(s):  
Lovisa Tobieson ◽  
Zita Czifra ◽  
Karin Wåhlén ◽  
Niklas Marklund ◽  
Bijar Ghafouri
Keyword(s):  
Intracerebral Hemorrhage ◽  
Human Brain ◽  
Protein Adsorption ◽  
Brain Tissue ◽  
Cerebral Microdialysis ◽  
Invasive Technique ◽  
Human Brain Tissue ◽  
Protein Patterns ◽  
Molecular Weight Range ◽  
Two Dimensional Gel Electrophoresis

Abstract Background Cerebral microdialysis (CMD) is a minimally invasive technique for sampling the interstitial fluid in human brain tissue. CMD allows monitoring the metabolic state of tissue, as well as sampling macromolecules such as proteins and peptides. Recovery of proteins or peptides can be hampered by their adsorption to the CMD membrane as has been previously shown in-vitro, however, protein adsorption to CMD membranes has not been characterized following implantation in human brain tissue. Methods In this paper, we describe the pattern of proteins adsorbed to CMD membranes compared to that of the microdialysate and of cerebrospinal fluid (CSF). We retrieved CMD membranes from three surgically treated intracerebral hemorrhage (ICH) patients, and analyzed protein adsorption to the membranes using two-dimensional gel electrophoresis (2-DE) in combination with nano-liquid mass spectrometry. We compared the proteome profile of three compartments; the CMD membrane, the microdialysate and ventricular CSF collected at time of CMD removal. Results We found unique protein patterns for each of the three compartments, particularly in the molecular weight range of 10-35 kDa. Conclusion This study highlights the importance of analyzing the membranes in addition to the microdialysate when using CMD to sample proteins for biomarker investigation.

Individualized blood pressure targets in the postoperative care of patients with intracerebral hemorrhage

2021 ◽  
pp. 1-10
Author(s):  
Anna Lindner ◽  
Verena Rass ◽  
Bogdan-Andrei Ianosi ◽  
Alois Josef Schiefecker ◽  
Mario Kofler ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Intracerebral Hemorrhage ◽  
Brain Tissue ◽  
Scale Score ◽  
Cerebral Metabolism ◽  
Cerebral Microdialysis ◽  
Early Management ◽  
Poor Grade ◽  
Intracerebral Pressure ◽  
Icu Discharge

OBJECTIVE Recent guidelines recommend targeting a systolic blood pressure (SBP) < 140 mm Hg in the early management of patients with spontaneous intracerebral hemorrhage (ICH). The optimal SBP targets for ICH patients after hematoma evacuation (HE) remain unclear. Here, the authors aimed to define the optimal SBP range based on multimodal neuromonitoring data. METHODS Forty poor-grade ICH patients who had undergone HE and then monitoring of intracerebral pressure, brain tissue oxygen tension (PbtO2), and cerebral metabolism (via cerebral microdialysis [CMD]) were prospectively included. Episodes of brain tissue hypoxia (BTH) (1-hour averaged PbtO2 < 20 mm Hg) and metabolic distress (CMD–lactate/pyruvate ratio [LPR] ≥ 40) were identified and linked to corresponding parameters of hemodynamic monitoring (SBP and cerebral perfusion pressure [CPP]). Multivariable regression analysis was performed using generalized estimating equations to identify associations between SBP levels, PbtO2, and brain metabolism. RESULTS The mean patient age was 60 (range 51–66) years and the median [IQR] initial ICH volume was 47 [29–60] ml. In multivariable models adjusted for Glasgow Coma Scale score, probe location, ICH volume, and age, lower SBP was independently associated with a higher risk of BTH (≤ 120 mm Hg: adjusted OR 2.9, p = 0.007; 120–130 mm Hg: adj OR 2.4, p = 0.002; 130–140 mm Hg: adj OR 1.6, p = 0.017) compared to a reference range of 140–150 mm Hg at the level of the foramen interventriculare Monroi, which corresponded to a CPP of 70–80 mm Hg and SBP levels between 150 and 160 mm Hg at the heart level. After exclusion of episodes with mitochondrial dysfunction, SBP targets < 140 mm Hg were associated with higher odds of cerebral metabolic distress (≤ 130 mm Hg: OR 2.5, p = 0.041; 130–140 mm Hg: OR 2.3, p = 0.033). Patients with a modified Rankin Scale score ≥ 5 at neurological ICU discharge more often exhibited BTH than patients with better outcomes (51% vs 10%, p = 0.003). CONCLUSIONS These data suggest that lower SPB and CPP levels are associated with a higher risk for BTH. Further studies are needed to evaluate whether a higher SPB target may prevent BTH and improve outcomes.

Chemokine detection in the cerebral tissue of patients with posttraumatic brain contusions

2008 ◽  
Vol 108 (5) ◽  
pp. 958-962 ◽  
Author(s):  
Roberto Stefini ◽  
Emanuela Catenacci ◽  
Simone Piva ◽  
Silvano Sozzani ◽  
Alessandra Valerio ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Head Trauma ◽  
Elective Surgery ◽  
Ribonuclease Protection Assay ◽  
Secondary Brain Injury ◽  
Mrna Levels ◽  
Severe Head Trauma ◽  
Cerebral Contusion ◽  
Surgical Evacuation ◽  
Secondary Injuries

Object The clinical outcome of patients with severe head injuries is still critically dependent on their secondary injuries. Although hypoxia and hypotension appear to mediate a substantial proportion of secondary injuries, many studies associate secondary brain injury with neuroinflammatory responses. Chemokines have been detected in the cerebrospinal fluid but not in the brain tissue of patients with head trauma. This study was performed to determine if chemokines were expressed in pericontusional brain tissue in patients with moderate or severe head trauma who underwent surgical evacuation of their brain contusions. Methods Twelve patients with posttraumatic cerebral contusion requiring a surgical evacuation were studied. A 20- to 40-mg sample of white matter was removed from the surgical cavity in the pericontusional area. Two patients undergoing elective surgery for clip ligation of an unruptured aneurysm were used as controls. The median interval from trauma to biopsy procedure was 44 hours (range 3–360 hours). Total RNA was isolated from these samples and a ribonuclease protection assay was performed to measure the mRNA levels of several chemokines: CCL2, CCL3, CCL4, CCL5, CXCL8, CXCL10, and XCL1. Results The CCL2, a monocyte chemoattractant produced by activated astrocytes, was the most strongly expressed chemokine, followed by CXCL8, CCL3, and CCL4. The chemokines CXCL10 and CCL5 were expressed at very low levels, and XCL1 was not detected. Conclusions Chemokine activation occurs early after moderate or severe head trauma and is maintained for several days after trauma. This event may contribute to neuroinflammatory exacerbation of posttraumatic brain damage in the pericontusional brain tissue.

scholarly journals Proteomic investigation of protein adsorption to cerebral microdialysis membranes in surgically treated intracerebral hemorrhage patients - a pilot study

2020 ◽  
Author(s):  
Lovisa Tobieson ◽  
Zita Czifra ◽  
Karin Wåhlén ◽  
Niklas Marklund ◽  
Bijar Ghafouri
Keyword(s):  
Intracerebral Hemorrhage ◽  
Human Brain ◽  
Protein Adsorption ◽  
Brain Tissue ◽  
Cerebral Microdialysis ◽  
Invasive Technique ◽  
Human Brain Tissue ◽  
Protein Patterns ◽  
Molecular Weight Range ◽  
Two Dimensional Gel Electrophoresis

Abstract Background: Cerebral microdialysis (CMD) is a minimally invasive technique for sampling the interstitial fluid in human brain tissue. CMD allows monitoring the metabolic state of tissue, as well as sampling macromolecules such as proteins and peptides. Recovery of proteins or peptides can be hampered by their adsorption to the CMD membrane as has been previously shown in-vitro, however, protein adsorption to CMD membranes has not been characterized following implantation in human brain tissue. Methods: In this paper, we describe the pattern of proteins adsorbed to CMD membranes compared to that of the microdialysate and of cerebrospinal fluid (CSF). We retrieved CMD membranes from three surgically treated intracerebral hemorrhage (ICH) patients, and analyzed protein adsorption to the membranes using two-dimensional gel electrophoresis (2-DE) in combination with nano-liquid mass spectrometry. We compared the proteome profile of three compartments; the CMD membrane, the microdialysate and ventricular CSF collected at time of CMD removal. Results: We found unique protein patterns in the molecular weight range of 10-35 kDa for each of the three compartments. Conclusion: This study highlights the importance of analyzing the membranes in addition to the microdialysate when using CMD to sample proteins for biomarker investigation.

Piper sarmentosum Roxb. Root Extracts Confer Neuroprotection by Attenuating Beta Amyloid-Induced Pro-Inflammatory Cytokines Released from Microglial Cells

2019 ◽  
Vol 16 (3) ◽  
pp. 251-260 ◽  
Author(s):  
Elaine Wan Ling Chan ◽  
Emilia Tze Ying Yeo ◽  
Kelly Wang Ling Wong ◽  
Mun Ling See ◽  
Ka Yan Wong ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Mrna Expression ◽  
Inflammatory Mediators ◽  
Beta Amyloid ◽  
Microglial Cells ◽  
Root Extracts ◽  
Tnf Α ◽  
P38α Mapk ◽  
Anti Inflammatory ◽  
Bv2 Microglial Cells

<P>Background: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder that eventually leads to severe cognitive impairment. Although the exact etiologies of AD still remain elusive, increasing evidence suggests that neuroinflammation cascades mediated by microglial cells are associated with AD. Piper sarmentosum Roxb. (PS) is a medicinal plant reported to possess various biological properties, including anti-inflammatory, anti-psychotic and anti-oxidant activity. However, little is known about the anti-inflammatory activity of PS roots despite their traditional use to treat inflammatory- mediated ailments. Objective: This study aimed to evaluate the anti-inflammatory and neuroprotective properties of extracts obtained from the roots of PS against beta-amyloid (Aβ)-induced microglial toxicity associated with the production of pro-inflammatory mediators. Method: BV2 microglial cells were treated with hexane (RHXN), dichloromethane (RDCM), ethyl acetate (REA) and methanol (RMEOH) extracts of the roots of PS prior to activation by Aβ. The production and mRNA expression of pro-inflammatory mediators were evaluated by Griess reagent, ELISA kits and RT-qPCR respectively. The phosphorylation status of p38α MAPK was determined via western blot assay. BV2 conditioned medium was used to treat SH-SY5Y neuroblastoma cells and the neuroprotective effect was assessed using MTT assay. Results: PS root extracts, in particular RMEOH significantly attenuated the production and mRNA expression of IL-1β, IL-6 and TNF-α in Aβ-induced BV2 microglial cells. In addition, RHXN, REA and RMEOH extracts significantly reduced nitric oxide (NO) level and the inhibition of NO production was correlated with the total phenolic content of the extracts. Further mechanistic studies suggested that PS root extracts attenuated the production of cytokines by regulating the phosphorylation of p38α MAPK in microglia. Importantly, PS root extracts have protective effects against Aβ-induced indirect neurotoxicity either by inhibiting the production of NO, IL-1β, IL-6, and TNF-α in BV2 cells or by protecting SHSY5Y cells against these inflammatory mediators. Conclusions: These findings provided evidence that PS root extracts confer neuroprotection against Aβ- induced microglial toxicity associated with the production of pro-inflammatory mediators and may be a potential therapeutic agent for inflammation-related neurological conditions including Alzheimer’s disease (AD).</P>

Sign in / Sign up

Export Citation Format

Share Document