scholarly journals The Cytokine Response to Human Traumatic Brain Injury: Temporal Profiles and Evidence for Cerebral Parenchymal Production

2010 ◽  
Vol 31 (2) ◽  
pp. 658-670 ◽  
Author(s):  
Adel Helmy ◽  
Keri LH Carpenter ◽  
David K Menon ◽  
John D Pickard ◽  
Peter JA Hutchinson
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Plasma Concentrations ◽  
Extracellular Fluid ◽  
Cd40 Ligand ◽  
Cerebral Microdialysis ◽  
Soluble Cd40 Ligand ◽  
Diverse Range

The role of neuroinflammation is increasingly being recognised in a diverse range of cerebral pathologies, including traumatic brain injury (TBI). We used cerebral microdialysis and paired arterial and jugular bulb plasma sampling to characterise the production of 42 cytokines after severe TBI in 12 patients over 5 days. We compared two microdialysis perfusates in six patients: central nervous system perfusion fluid and 3.5% human albumin solution (HAS); 3.5% HAS has a superior fluid recovery (95.8 versus 83.3%), a superior relative recovery in 18 of 42 cytokines (versus 8 of 42), and a qualitatively superior recovery profile. All 42 cytokines were recovered from the human brain. Sixteen cytokines showed a stereotyped temporal peak, at least twice the median value for that cytokine over the monitoring period; day 1: tumour necrosis factor, interleukin (IL)7, IL8, macrophage inflammatory protein (MIP)1α, soluble CD40 ligand, GRO, IL1β, platelet derived growth factor (PDGF)-AA, MIP1β, RANTES; day 2: IL1 receptor antagonist (ra). IL6, granulocyte-colony stimulating factor (G-CSF), chemokine CXC motif ligand 10 (IP10); days 4 to 5: IL12p70, IL10. Brain extracellular fluid concentrations were significantly higher than plasma concentrations for 19 cytokines: basic fibroblast growth factor (FGF2), G-CSF, IL1α, IL1 β, IL1ra, IL3, IL6, IL8, IL10, IL12p40, IL12p70, IP10, monocyte chemotactic protein (MCP)1, MCP3, MIP1α, MIP1β, PDGF-AA, transforming growth factor (TGF)α and vascular endothelial growth factor. No clear arterio-jugular venous gradients were apparent. These data provide evidence for the cerebral production of these cytokines and show a stereotyped temporal pattern after TBI.

scholarly journals THE DIAGNOSTIC VALUE OF PLATELET-DERIVED FACTOR PDGF-BB AND ST2 IN HEART REJECTION

2017 ◽  
Vol 18 (4) ◽  
pp. 71-76
Author(s):  
O. P. Shevchenko ◽  
A. A. Ulybysheva ◽  
A. V. Aksyonova ◽  
N. P. Mozhejko ◽  
E. A. Stakhanova ◽  
...  
Keyword(s):  
Growth Factor ◽  
Predictive Value ◽  
Plasma Concentrations ◽  
Cd40 Ligand ◽  
Diagnostic Value ◽  
Platelet Derived Growth Factor ◽  
Humoral Rejection ◽  
Soluble Cd40 Ligand ◽  
Cardiac Biomarker ◽  
And Gender

Aim: to determine the association between plasma concentrations of biomarkers (sCD40L, PDGF-BB, PlGF-1, ST2) with histochemical and immunohistochemical signs of heart rejection.Materials and methods.The study included 98 heart recipients aged from 12 to 69 (mean age 43 ± 14) years, of which 78 men. In 68 patients dilated cardiomyopathy was diagnosed, 30 recipients were diagnosed with coronary heart disease. The concentrations of placental growth factor (PlGF-1), platelet-derived growth factor (PDGF-BB), soluble CD40 ligand (sCD40L) were measured using xMAP technology. The concentrations of ST2 cardiac biomarker were measured by ELISA.Results.No correlation was found between the levels of biomarkers (sCD40L, PDGF-BB, PlGF-1, ST2) and gender, age and diagnosis. The rejection was diagnosed via biopsy in 49 biopsies taken from 37 recipients. 1A rejection was found in 25 patients (34 biopsies), 1B rejection was identifi ed in 2 patients (3 biopsies), 3A rejection was diagnosed in 4 patients. Immunohistochemical signs of humoral rejection were identifi ed in 3 patients. The combination of acute cellular and humoral rejection was found in 4 patients (5 biopsies). The PDGFBB level was measured at the same day as the biopsy was taken, and it was shown to be signifi cantly higher in patients with rejection (p = 0.02). Rejection frequency was signifi cantly higher in patients with high PDGF-BB level (≥2473.7 pg/ml, RR = 1.64 ± 0.23; 95% CI [1.03–2.61]). Rejection frequency increased to 2.11 ± 0.34 [95% CI [1.08–4.11]] in recipients with ST2 and PDGF-BB concentration higher than the median value. The highest predictive value for heart rejection can be reached by a panel of three biomarkers: sCD40L, PlGF-1 and ST2 (RR = 2.51 ± 0.38; 95% CI [1.18–5.3]).Conclusion. PDGF-BB has moderate predictive value for heart rejection. The highest predictive value for heart rejection was reached by a panel of three biomarkers: sCD40L, PlGF-1 and ST2.

scholarly journals Recombinant Human Interleukin-1 Receptor Antagonist in Severe Traumatic Brain Injury: A Phase II Randomized Control Trial

2014 ◽  
Vol 34 (5) ◽  
pp. 845-851 ◽  
Author(s):  
Adel Helmy ◽  
Mathew R Guilfoyle ◽  
Keri LH Carpenter ◽  
John D Pickard ◽  
David K Menon ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Receptor Antagonist ◽  
Phase Ii ◽  
Interleukin 1 ◽  
Safety Data ◽  
Extracellular Fluid ◽  
Cerebral Microdialysis ◽  
Interleukin 1 Receptor Antagonist ◽  
Randomized Control

Traumatic brain injury (TBI) is the commonest cause of death and disability in those aged under 40 years. Interleukin-1 receptor antagonist (IL1ra) is an endogenous competitive antagonist at the interleukin-1 type-1 receptor (IL-1R). Antagonism at the IL-1R confers neuroprotection in several rodent models of neuronal injury (i.e., trauma, stroke and excitotoxicity). We describe a single center, phase II, open label, randomized-control study of recombinant human IL1ra (rhIL1ra, anakinra) in severe TBI, at a dose of 100 mg subcutaneously once a day for 5 days in 20 patients randomized 1:1. We provide safety data (primary outcome) in this pathology, utilize cerebral microdialysis to directly determine brain extracellular concentrations of IL1ra and 41 cytokines and chemokines, and use principal component analysis (PCA) to explore the resultant cerebral cytokine profile. Interleukin-1 receptor antagonist was safe, penetrated into plasma and the brain extracellular fluid. The PCA showed a separation in cytokine profiles after IL1ra administration. A candidate cytokine from this analysis, macrophage-derived chemoattractant, was significantly lower in the rh I Lira-treated group. Our results provide promising data for rhIL1ra as a therapeutic candidate by showing safety, brain penetration and a modification of the neuroinflammatory response to TBI by a putative neuroprotective agent in humans for the first time.

IMPACT probability of poor outcome and plasma cytokine concentrations are associated with multiple organ dysfunction syndrome following traumatic brain injury

2019 ◽  
Vol 131 (6) ◽  
pp. 1931-1937 ◽  
Author(s):  
Sungho Lee ◽  
Hyunsoo Hwang ◽  
Jose-Miguel Yamal ◽  
J. Clay Goodman ◽  
Imoigele P. Aisiku ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Organ Dysfunction ◽  
Multiple Organ Dysfunction Syndrome ◽  
Sofa Score ◽  
Plasma Concentrations ◽  
Multiple Organ ◽  
Multiple Organ Dysfunction ◽  
Poor Outcome ◽  
Initial Plasma

OBJECTIVETraumatic brain injury (TBI) is a major cause of morbidity and mortality. Multiple organ dysfunction syndrome (MODS) occurs frequently after TBI and independently worsens outcome. The present study aimed to identify potential admission characteristics associated with post-TBI MODS.METHODSThe authors performed a secondary analysis of a recent randomized clinical trial studying the effects of erythropoietin and blood transfusion threshold on neurological recovery after TBI. Admission clinical, demographic, laboratory, and imaging parameters were used in a multivariable Cox regression analysis to identify independent risk factors for MODS following TBI, defined as maximum total Sequential Organ Failure Assessment (SOFA) score > 7 within 10 days of TBI.RESULTSTwo hundred patients were initially recruited and 166 were included in the final analysis. Respiratory dysfunction was the most common nonneurological organ system dysfunction, occurring in 62% of the patients. International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) probability of poor outcome at admission was significantly associated with MODS following TBI (odds ratio [OR] 8.88, 95% confidence interval [CI] 1.94–42.68, p < 0.05). However, more commonly used measures of TBI severity, such as the Glasgow Coma Scale, Injury Severity Scale, and Marshall classification, were not associated with post-TBI MODS. In addition, initial plasma concentrations of interleukin (IL)–6, IL-8, and IL-10 were significantly associated with the development of MODS (OR 1.47, 95% CI 1.20–1.80, p < 0.001 for IL-6; OR 1.26, 95% CI 1.01–1.58, p = 0.042 for IL-8; OR 1.77, 95% CI 1.24–2.53, p = 0.002 for IL-10) as well as individual organ dysfunction (SOFA component score ≥ 1). Finally, MODS following TBI was significantly associated with mortality (OR 5.95, 95% CI 2.18–19.14, p = 0.001), and SOFA score was significantly associated with poor outcome at 6 months (Glasgow Outcome Scale score < 4) when analyzed as a continuous variable (OR 1.21, 95% CI 1.06–1.40, p = 0.006).CONCLUSIONSAdmission IMPACT probability of poor outcome and initial plasma concentrations of IL-6, IL-8, and IL-10 were associated with MODS following TBI.

scholarly journals Metabolic Crisis without Brain Ischemia is Common after Traumatic Brain Injury: A Combined Microdialysis and Positron Emission Tomography Study

2005 ◽  
Vol 25 (6) ◽  
pp. 763-774 ◽  
Author(s):  
Paul Vespa ◽  
Marvin Bergsneider ◽  
Nayoa Hattori ◽  
Hsiao-Ming Wu ◽  
Sung-Cheng Huang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Positron Emission Tomography ◽  
Brain Injury ◽  
Brain Ischemia ◽  
Emission Tomography ◽  
Cerebral Microdialysis ◽  
Energy Crisis ◽  
Metabolic Crisis ◽  
Positron Emission ◽  
Pyruvate Ratio

Brain trauma is accompanied by regional alterations of brain metabolism, reduction in metabolic rates and possible energy crisis. We hypothesize that microdialysis markers of energy crisis are present during the critical period of intensive care despite the absence of brain ischemia. In all, 19 brain injury patients (mean GCS 6) underwent combined positron emission tomography (PET) for metabolism of glucose (CMRglu) and oxygen (CMRO2) and cerebral microdialysis (MD) at a mean time of 36 h after injury. Microdialysis values were compared with the regional mean PET values adjacent to the probe. Longitudinal MD data revealed a 25% incidence rate of metabolic crisis (elevated lactate/pyruvate ratio (LPR)>40) but only a 2.4% incidence rate of ischemia. Positron emission tomography imaging revealed a 1% incidence of ischemia across all voxels as measured by oxygen extraction fraction (OEF) and cerebral venous oxygen content (CvO2). In the region of the MD probe, PET imaging revealed ischemia in a single patient despite increased LPR in other patients. Lactate/pyruvate ratio correlated negatively with CMRO2 ( P<0.001), but not with OEF or CvO2. Traumatic brain injury leads to a state of persistent metabolic crisis as reflected by abnormal cerebral microdialysis LPR that is not related to ischemia.

Hypothermia Attenuates the Normal Increase in Interleukin 1β RNA and Nerve Growth Factor Following Traumatic Brain Injury in the Rat

1995 ◽  
Vol 12 (2) ◽  
pp. 159-167 ◽  
Author(s):  
JAMES R. GOSS ◽  
SCOT D. STYREN ◽  
PETER D. MILLER ◽  
PATRICK M. KOCHANEK ◽  
ALAN M. PALMER ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Nerve Growth Factor ◽  
Brain Injury ◽  
Growth Factor ◽  
Interleukin 1Β ◽  
Nerve Growth ◽  
Normal Increase
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