interleukin-8 and Brain-Injuries

Neuroinflammation occuring after traumatic brain injury (TBI) is a complex phenomenon comprising distinct cellular and molecular events involving the injured as well as the healthy cerebral tissue. Although immunoactivation only represents a one of the many cascades initiated in the pathophysiology of TBI, the exact function of each mediator, activated cell types or pathophysiological mechanism, needs to be further elucidated. It is widely accepted that inflammatory events display dual and opposing roles promoting, on the one hand, the repair of the injured tissue and, on the other hand, causing additional brain damage mediated by the numerous neurotoxic substances released. Most of the data supporting these hypotheses derive from experimental work based on both animal models and cultured neuronal cells. More recently, evidence has been provided that a complete elimination of selected inflammatory mediators is rather detrimental as shown by the attenuation of neurological recovery. However, there are conflicting results reported on this issue which strongly depend on the experimental setting used. The history of immunoactivation in neurotrauma is the subject of this review article, giving particular emphasis to the comparison of clinical versus experimental studies performed over the last 10 years. These results also are evaluated with respect to other neuropathologies, which are years ahead as compared to the research in TBI. The possible reciprocal influence of peripheral and intrathecal activation of the immune system will also be discussed. To conclude, the future directions of research in the field of neurotrauma is considered.

Topics: Animals; Brain; Brain Injuries; Cell Death; Complement C3; Cytokines; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Transforming Growth Factor beta

Topics: Biomarkers; Brain Injuries; Humans; Interleukin-8; Meningitis, Bacterial; Prognosis

To investigate the effect and its possible mechanisms of Danhong Injection (DHI) on cerebral injury during coronary artery bypass graft (CABG) operation with hypothermic cardiopulmonary bypass (CPB).. Fifty patients went to CABG with CPB were randomly assigned equally to two groups, the control group and the tested group. DHI 1.5 mL/kg was pumped to where the tested group at the times of aortic pre-charging and unclamping respectively, but to the control group, equal volume of normal saline was given instead. Blood samples were taken from jugular bulb at different time points, i. e. before operation (T1, baseline), re-warming to 36 degrees C (T2 ), 30 min (T3 ) and 6 h (T4) after terminating CPB, for determination levels of superoxide dismutase (SOD) activity using xanthine oxidase method, malondialdehyde (MDA) concentration using thiobarbituric method, tumor necrosis factor alpha (TNF-alpha), as well as interleukin-6, -8 using radioimmunoassay and -10 (IL-6, IL-8 and IL-10) using ELISA.. Level of SOD activity significantly decreased during (T2) and after CPB (T3 and T4) in the control group, as compared to the T1 (P < 0.01), but it was unchanged in the tested group; level of MDA increased during and after CPB in both groups (P < 0.01), but more significantly in the control group (P < 0.05), so comparison after CPB between the two groups showed a higher SOD and lower MDA level in the tested group. Plasma levels of TNF-alpha, IL-6, IL-8 and IL-10 significantly increased in both groups after CPB (T3 and T4, P < 0.01) as compared to the T1, but the comparison between groups showed lower plasma TNF-alpha, IL-6 and IL-8 levels at T3 and T4, and higher IL-10 level at T4 in the test group (P < 0.01). All patients had stable life signs with no occurrence of adverse reaction.. DHI has obvious protective effect on cerebral injury in patients undergoing CABG with CPB, the mechanisms may be associated with the actions of anti-oxidation, anti-inflammation and regulation on immune factors.

Topics: Aged; Brain Injuries; Coronary Artery Bypass; Drugs, Chinese Herbal; Extracorporeal Circulation; Female; Humans; Injections; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged

To determine the association of gestational age (GA) and day of life (DOL) with the circulating serum concentration of six brain injury-associated biomarkers in non-brain injured neonates born between 23 and 41 weeks' GA.. In a multicenter prospective observational cohort study, serum CNS-insult, inflammatory and trophic proteins concentrations were measured daily in the first 7 DOL.. Overall, 3232 serum samples were analyzed from 745 enrollees, median GA 32.3 weeks. BDNF increased 3.7% and IL-8 increased 8.9% each week of gestation. VEGF, IL-6, and IL-10 showed no relationship with GA. VEGF increased 10.8% and IL-8 18.9%, each DOL. IL-6 decreased by 15.8% each DOL. IL-10 decreased by 81.4% each DOL for DOL 0-3. BDNF did not change with DOL. Only 49.67% of samples had detectable GFAP and 33.15% had detectable NRGN. The odds of having detectable GFAP and NRGN increased by 53% and 11%, respectively, each week after 36 weeks' GA. The odds of having detectable GFAP and NRGN decreased by 15% and 8%, respectively, each DOL.. BDNF and IL-8 serum concentrations vary with GA. VEGF and interleukin concentrations are dynamic in the first week of life, suggesting circulating levels should be adjusted for GA and DOL for clinically relevant assessment of brain injury.. Normative data of six brain injury-related biomarkers is being proposed. When interpreting serum concentrations of brain injury biomarkers, it is key to adjust for gestational age at birth and day of life during the first week to correctly assess for clinical brain injury in neonates. Variation in levels of some biomarkers may be related to gestational and postnatal age and not necessarily pathology.

Topics: Biomarkers; Brain Injuries; Brain-Derived Neurotrophic Factor; Gestational Age; Humans; Infant, Newborn; Interleukin-10; Interleukin-6; Interleukin-8; Prospective Studies; Vascular Endothelial Growth Factor A

To study the protective effect of breviscapine against brain injury induced by intrauterine inflammation in preterm rats and its mechanism.. A preterm rat model of brain injury caused by intrauterine inflammation was prepared by intraperitoneal injections of lipopolysaccharide in pregnant rats. The pregnant rats and preterm rats were respectively randomly divided into 5 groups: control, model, low-dose breviscapine (45 mg/kg), high-dose breviscapine (90 mg/kg), and high-dose breviscapine (90 mg/kg)+ML385 [a nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor, 30 mg/kg] (. Pathological injury was found in the uterus, and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, and severe microglia pyroptosis occurred in the cerebral cortex of the offspring rats in the model group. Compared with the control group, the model group had significant reductions in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and heme oxygenase-1 (HO-1) in the brain tissue of the offspring rats (. Breviscapine can inhibit inflammatory response in brain tissue of preterm rats caused by intrauterine inflammation by activating the Nrf2 pathway, and it can also inhibit microglial pyroptosis and alleviate brain injury.

Topics: Animals; Body Weight; Brain Injuries; Caspase 1; Female; Flavonoids; Inflammation; Interleukin-6; Interleukin-8; NF-E2-Related Factor 2; NLR Family, Pyrin Domain-Containing 3 Protein; Pregnancy; Rats

Lipid peroxidation represents a marker of secondary brain injury both in traumatic and in non-traumatic conditions-as in major neurosurgical procedures-eventually leading to brain edema amplification and further brain damage. Malondialdehyde (MDA), a lipid peroxidation marker, and ascorbate, a marker of antioxidant status, can represent early indicators of this process within the cerebrospinal fluid (CSF). We hypothesized that changes in cerebral lipid peroxidation can be measured ex vivo following neurosurgery in children.. Thirty-six children (M:F = 19/17, median age 32.9 months; IQR 17.6-74.6) undergoing neurosurgery for brain tumor removal were admitted to the pediatric intensive care unit (PICU) in the postoperative period with an indwelling intraventricular catheter for intracranial pressure monitoring and CSF drainage. Plasma and CSF samples were obtained for serial measurement of MDA, ascorbate, and cytokines.. An early brain-limited increase in lipid peroxidation was measured, with a significant increase from baseline of MDA in CSF (p = 0.007) but not in plasma. In parallel, ascorbate in CSF decreased (p = 0.05). Systemic inflammatory response following brain surgery was evidenced by plasma IL-6/IL-8 increase (p 0.0022 and 0.0106, respectively). No correlation was found between oxidative response and tumor site or histology (according to World Health Organization grading). Similarly, lipid peroxidation was unrelated to the length of surgery (mean 321 ± 73 min), or intraoperative blood loss (mean 20.9 ± 16.8% of preoperative volemia, 44% given hemotransfusions). Median PICU stay was 3.5 days (IQL range 2-5.5 d.), and postoperative ventilation need was 24 h (IQL range 20-61.5 h). The elevation in postoperative MDA in CSF compared with preoperative values correlated significantly with postoperative ventilation need (P = 0.05, r. Our results indicate that lipid peroxidation increases consistently following brain surgery, and it is accompanied by a decrease in antioxidant defences; intraventricular catheterization offers a unique chance of oxidative process monitoring. Further studies are needed to evaluate whether monitoring post-neurosurgical oxidative stress in CSF is of prognostic utility.

Topics: Antioxidants; Ascorbic Acid; Brain Injuries; Brain Neoplasms; Child; Child, Preschool; Cytokines; Drainage; Female; Humans; Infant; Intensive Care Units, Pediatric; Interleukin-6; Interleukin-8; Intracranial Pressure; Lipid Peroxidation; Male; Malondialdehyde; Monitoring, Physiologic; Neurosurgical Procedures; Oxidative Stress; Postoperative Complications; Respiration, Artificial

In a clinical trial of cerebral palsy, the level of plasma interleukin-8 (IL-8) was increased, correlated with motor improvement, after human umbilical cord blood mononuclear cell (hUCBC) infusion. This study aimed to elucidate the role of IL-8 in the therapeutic effects of hUCBCs in a mouse model of hypoxic-ischaemic brain injury (HI). In P7 HI mouse brains, hUCBC administration at day 7 after HI upregulated the gene expression of Cxcl2, the mouse IL-8 homologue and increased the expression of its receptor, CXCR2. hUCBC administration restored the sequential downstream signalling axis of p-p38/p-MAPKAPK2, NFκB, and angiogenic factors, which were downregulated by HI. An in vitro assay revealed the downregulation of the angiogenic pathway by CXCR2 knockdown and p38 inhibition. In vivo p38 inhibition prior to hUCBC administration in HI mouse brains produced identical results. Behavioural outcomes revealed a therapeutic effect (ps < 0.01) of hUCBC or IL-8 administration, which was correlated with decreases in infarct size and angiogenic findings in the striatum. In conclusion, the response of the host to hUCBC administration in mice upregulated Cxcl2, which led to the activation of the IL-8-mediated p-p38 signalling pathway. The upregulation of the downstream pathway and angiogenic growth factors via NFκB can be inferred to be the potential therapeutic mechanism of hUCBCs.

Topics: Animals; Animals, Newborn; Brain Injuries; Cells, Cultured; Cord Blood Stem Cell Transplantation; Disease Models, Animal; Human Umbilical Vein Endothelial Cells; Humans; Hypoxia-Ischemia, Brain; Intercellular Signaling Peptides and Proteins; Interleukin-8; Leukocytes, Mononuclear; Mice; Neovascularization, Physiologic

Clinical investigations lack predictive value when diagnosing pneumonia, especially when patients are ventilated and develop ventilator associated pneumonia (VAP). New tools to aid diagnosis are important to improve outcomes. This pilot study examines the potential for a panel of inflammatory mediators to aid in the diagnosis. Forty-four ventilated patients, 17 with pneumonia and 27 with brain injuries, eight of whom developed VAP, were recruited. 51 inflammatory mediators, including cytokines and oxylipins, were measured in patients' serum using flow cytometry and mass spectrometry. The mediators could separate patients admitted to ICU with pneumonia compared to brain injury with an area under the receiver operating characteristic curve (AUROC) 0.75 (0.61-0.90). Changes in inflammatory mediators were similar in both groups over the course of ICU stay with 5,6-dihydroxyeicosatrienoic and 8,9-dihydroxyeicosatrienoic acids increasing over time and interleukin-6 decreasing. However, brain injured patients who developed VAP maintained inflammatory profiles similar to those at admission. A multivariate model containing 5,6-dihydroxyeicosatrienoic acid, 8,9-dihydroxyeicosatrienoic acid, intercellular adhesion molecule-1, interleukin-6, and interleukin-8, could differentiate patients with VAP from brain injured patients without infection (AUROC 0.94 (0.80-1.00)). The use of a selected group of markers showed promise to aid the diagnosis of VAP especially when combined with clinical data.

Topics: Biomarkers; Brain Injuries; Critical Care; Female; Flow Cytometry; Humans; Inflammation; Intensive Care Units; Interleukin-6; Interleukin-8; Male; Mass Spectrometry; Middle Aged; Pneumonia, Ventilator-Associated; ROC Curve

To explore the relationship between histological chorioamnionitis (HCA) and fetal inflammatory response syndrome (FIRS) and brain injury in preterm infants.. One hundred and three singleton infants with premature rupture of membranes (PROM) (gestation ages of less than 34 weeks) were enrolled. All the placentas were submitted for pathological evaluation. Umbilical cord blood interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor alpha (TNF-α) and granulocyte-colony stimulating factor (G-CSF) levels were measured with liquid chip. All preterm infants accepted brain imaging examinations. Based on the placental pathological examination and umbilical cord blood level of IL-6, the 103 infants were classified into HCA⁻ FIRS⁻, HCA⁺ FIRS⁻, and HCA⁺ FIRS⁺ groups.. The incidences of HCA, FIRS, and brain injury were 53.4%, 20.4% and 38.8% respectively. The prevalence of brain injury in HCA⁻ FIRS⁻, HCA⁺ FIRS⁻, and HCA⁺ FIRS⁺ cases was 21%, 41%, and 76% respectively (P<0.01). The grade 2 and grade 3 of placental inflammation and the inflammation at stage 2 and stage 3 increased the risk of brain injury. The cord blood levels of IL-8, TNF-α, and G-CSF in the HCA⁺ FIRS⁺ group were significantly higher than in the other two groups, and the levels of the above parameters in the HCA⁺ FIRS⁻ were higher than in the HCA⁻ FIRS⁻ group (P<0.05).. Placental inflammation and FIRS are associated with brain injury in preterm infants. Preterm infants exposed to severe placental inflammation have an increased risk of brain injury. Cord blood IL-8, TNF-α and G-CSF may be involved in the process of brain injury in preterm infants with placental inflammation and FIRS.

Topics: Brain Injuries; Chorioamnionitis; Female; Granulocyte Colony-Stimulating Factor; Humans; Infant, Newborn; Infant, Premature; Inflammation; Interleukin-8; Male; Placenta; Pregnancy; Tumor Necrosis Factor-alpha

Many studies suggest that hyperbaric oxygen therapy (HBOT) can provide some clinically curative effects on blast-induced traumatic brain injury (bTBI). The specific mechanism by which this occurs still remains unknown, and no standardized time or course of hyperbaric oxygen treatment is currently used. In this study, bTBI was produced by paper detonators equivalent to 600 mg of TNT exploding at 6.5 cm vertical to the rabbit's head. HBO (100% O2 at 2.0 absolute atmospheres) was used once, 12 h after injury. Magnetic resonance spectroscopy was performed to investigate the impact of HBOT on the metabolism of local injured nerves in brain tissue. We also examined blood-brain barrier (BBB) integrity, brain water content, apoptotic factors, and some inflammatory mediators. Our results demonstrate that hyperbaric oxygen could confer neuroprotection and improve prognosis after explosive injury by promoting the metabolism of local neurons, inhibiting brain edema, protecting BBB integrity, decreasing cell apoptosis, and inhibiting the inflammatory response. Furthermore, timely intervention within 1 week after injury might be more conducive to improving the prognosis of patients with bTBI.

Topics: Animals; Blood-Brain Barrier; Brain; Brain Edema; Brain Injuries; Caspase 3; Encephalitis; Hyperbaric Oxygenation; Interleukin-8; Male; Rabbits; Tumor Necrosis Factor-alpha

Despite the involvement of cytokine production in neurotrauma, there is still controversy regarding cytokines levels and clinical outcome following severe traumatic brain injury (TBI).. The present study was designed to investigate whether cytokine levels (of IL-1β, IL-6, IL-8, IL-10, IL-12p70 and TNF-α) are associated with primary outcome (death or survival) after severe TBI.. This prospective study enrolled 24 male patients, victims of severe TBI. Venous blood samples were taken in the Intensive Care Unit (ICU) (study entry), 24 and 48 hours later. Plasma cytokine levels were assayed by flow cytometry.. Severe TBI was associated with a 42% mortality rate. TBI patients had a significant increase in the levels of all cytokines measured, except for IL-1β, compared to controls. Statistically significant increases in the IL-10, -8 and -6 levels were observed in the non-survivors TBI patients compared to the survivors sub-group measured in the first sample (study entry) and in the subsequent sample (24 hours later). There were no significant differences in IL-1β, TNF-α and IL-12p70 levels between survivors and non-survivors in any time sampled.. The findings indicate that increased IL-10, -8 and -6 levels may constitute an early predictor of unfavourable outcome in severe TBI patients.

Topics: Adolescent; Adult; Biomarkers; Brain Injuries; Brazil; Child; Female; Glasgow Coma Scale; Humans; Inflammation; Interleukin-10; Interleukin-12; Interleukin-6; Interleukin-8; Male; Middle Aged; Prognosis; Prospective Studies; Survival Analysis; Tumor Necrosis Factor-alpha

The present study aimed to investigate the effect of RNA interference (RNAi) on the inhibition of interleukin (IL)‑6 expression in rat cerebral gliocytes in vitro and rat cerebral traumatic tissues in vivo, as well as the effect of RNAi on cerebral edema. pSUPER vectors containing IL‑6 small hairpin RNA (pSUPER‑IL‑6 1‑5) were designed, constructed and transfected into C6 rat glioma cells using cationic liposomes. ELISA was used to select the plasmid with the strongest interference effect. A freefall method was used to generate a rat brain injury model and rats were randomly divided into treatment, empty plasmid and control groups (n=14/group). IL‑6 levels, water content and sodium content were determined in the brain tissues at 24 and 72 h post‑injury. pSUPER‑IL‑6 was effectively transfected into C6 cells and was found to inhibit the expression of IL‑6 rather than IL‑8. The pSUPER‑IL‑6 1 vector was most effective in inducing RNAi. In vivo, IL‑6 levels were observed to be lowest in the interference group and there were statistically significant differences in water and sodium content among the experimental groups (P<0.05). RNAi was found to inhibit IL‑6 expression in vivo and in vitro in rat cerebral gliocytes, and the reduction of the IL‑6 levels was found to reduce post‑traumatic cerebral edema.

Topics: Animals; Brain; Brain Injuries; Cell Line, Tumor; Glioma; Interleukin-6; Interleukin-8; Male; Plasmids; Rats; Rats, Sprague-Dawley; RNA Interference; RNA, Small Interfering; Sodium

The onset of mechanical ventilation is a critical time for the initiation of cerebral white matter (WM) injury in preterm neonates, particularly if they are inadvertently exposed to high tidal volumes (VT) in the delivery room. Protective ventilation strategies at birth reduce ventilation-induced lung and brain inflammation and injury, however its efficacy in a compromised newborn is not known. Chorioamnionitis is a common antecedent of preterm birth, and increases the risk and severity of WM injury. We investigated the effects of high VT ventilation, after chorioamnionitis, on preterm lung and WM inflammation and injury, and whether a protective ventilation strategy could mitigate the response.. Pregnant ewes (n = 18) received intra-amniotic lipopolysaccharide (LPS) 2 days before delivery, instrumentation and ventilation at 127±1 days gestation. Lambs were either immediately euthanased and used as unventilated controls (LPSUVC; n = 6), or were ventilated using an injurious high VT strategy (LPSINJ; n = 5) or a protective ventilation strategy (LPSPROT; n = 7) for a total of 90 min. Mean arterial pressure, heart rate and cerebral haemodynamics and oxygenation were measured continuously. Lungs and brains underwent molecular and histological assessment of inflammation and injury.. LPSINJ lambs had poorer oxygenation than LPSPROT lambs. Ventilation requirements and cardiopulmonary and systemic haemodynamics were not different between ventilation strategies. Compared to unventilated lambs, LPSINJ and LPSPROT lambs had increases in pro-inflammatory cytokine expression within the lungs and brain, and increased astrogliosis (p<0.02) and cell death (p<0.05) in the WM, which were equivalent in magnitude between groups.. Ventilation after acute chorioamnionitis, irrespective of strategy used, increases haemodynamic instability and lung and cerebral inflammation and injury. Mechanical ventilation is a potential contributor to WM injury in infants exposed to chorioamnionitis.

Topics: Animals; Animals, Newborn; Brain; Brain Injuries; Chorioamnionitis; Female; Gene Expression; Glial Fibrillary Acidic Protein; Hemodynamics; Immunohistochemistry; Inflammation Mediators; Interleukin-1beta; Interleukin-6; Interleukin-8; Lung Injury; Pregnancy; Premature Birth; Respiration, Artificial; Reverse Transcriptase Polymerase Chain Reaction; Sheep; Sheep Diseases

To examine the association among interleukin-6, interleukin-8, tumor necrosis factor-α, interleukin-10, and interleukin-1β and white matter injury in very-low-birth-weight infants with clinical sepsis and to help predict infants at risk for development of white matter injury.. A prospective cohort study was carried out.. Neonatal intensive care unit.. Very low birth weight infants with clinical early-onset sepsis. Exclusion criteria were death before 14 days, major malformations, and congenital infections.. Ultrasound brain scans were carried out on the third day and weekly until the sixth week of life or discharge and confirmed by a magnetic resonance image performed in the first year. Plasma was assayed for interleukin-6, interleukin-8, tumor necrosis factor-α, interleukin-10, and interleukin-1β in the same sample collected for sepsis work-up. Mann-Whitney, chi-square, t tests, multiple regression, and receiver operating characteristic analysis were applied.. From July 2005 to October 2007 we studied 84 very-low-birth-weight infants, 27 (32%) with white matter injury, and 57 (68%) control subjects (with no white matter injury). Proven early-onset sepsis and necrotizing enterocolitis were high risk for white matter injury after adjustment for gestational age and birth weight (relative risk, 3.04; 1.93-4.80 and relative risk, 2.2; 1.31-3.74, respectively). Interleukin-6, interleukin-8, and tumor necrosis factor-α levels were higher in infants with white matter injury than in control subjects (p < .0001). Interleukin-1β and interleukin-10 were similar. The areas under the curve for interleukin-6, interleukin-8, and tumor necrosis factor-α were 0.96 (0.92-0.99), 0.97 (0.94-1.0), and 0.93 (0.86-0.99), respectively. Interleukin-8 ≥100 pg/mL was the best predictor of white matter injury; the sensitivity and specificity were 96% and 83%, respectively, and negative predictive value was 98%.. Very-low-birth-weight infants with proven early-onset sepsis, necrotizing enterocolitis, and high plasma levels of interleukin-6, interleukin-8, and tumor necrosis factor-α are at high risk for white matter injury.

Topics: Brain Injuries; Cytokines; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Leukoencephalopathies; Male; Prospective Studies; Risk Factors; Sepsis; Tumor Necrosis Factor-alpha; Ultrasonography

The management of severe traumatic brain injury (TBI) focuses on prevention and treatment of intracranial hypertension (ICH) and cerebral hypoperfusion (CH). Predicting which patients will develop these secondary insults is currently not possible. This study investigates the systemic manifestation of neuroinflammation and its role in helping to predict clinical deterioration following severe TBI. Patients with head Abbreviated Injury Severity greater than 3, age older than 14 years, "isolated" TBI, and placement of intracranial pressure monitor were prospectively enrolled. Serum was collected within 24 h and twice daily for 7 days. Measures of moderate and severe ICH (intracranial pressure >20 and >30 mmHg) and moderate and severe CH (cerebral perfusion pressure <60 and <50 mmHg) were compared with interleukin 8 (IL-8) and tumor necrosis factor α (TNF-α) levels drawn before periods of monitoring. An adjusted mixed-model analysis accounting for longitudinal correlations was applied. Sixty-eight patients were enrolled; 670 12-h periods of monitoring and 845 serum samples were available for analysis. Associations were found between serum levels of IL-8 and moderate and severe CH. Levels of TNF-α and severe ICH and CH were also correlated. Specificities of 81% to 95% were found for prediction of ICH and CH for TNF-α and CH for IL-8. Interleukin 8 and TNF-α demonstrate promise as candidate serum markers of impending ICH and CH. This suggests that we may be able to "predict" imminent events following TBI before clinical manifestations. Given the morbidity of ICH and CH, minimizing the effects of these secondary insults may have a significant impact on outcome and help guide decisions about timing of interventions.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Brain Injuries; Cerebrovascular Circulation; Female; Humans; Interleukin-8; Intracranial Hypertension; Male; Middle Aged; Sensitivity and Specificity; Tumor Necrosis Factor-alpha; Young Adult

To determine the evolution of cytokine patterns using microdialysis in patients with traumatic brain injury with diffuse lesions and to study the relationship between cytokines and intracranial pressure, brain tissue oxygenation and lesion type on the computed cranial tomography scan (patients with and without brain swelling).. Prospective and observational study.. Third-level university hospital.. Patients between 15 and 65 yrs with severe traumatic brain injury and a diffuse lesion requiring intracranial pressure and brain tissue oxygenation monitoring were eligible.. Microdialysis catheters with a high-cutoff membrane of 100 kDa were inserted.. Sixteen patients were included in the analysis. There was a substantial interindividual variability between cytokine values. The highest concentrations for the interleukin-1β, interleukin-6, and interleukin-8 were measured during the first 24 hrs followed by a gradual decline. The average concentration for interleukin-10 did not vary over time. This pattern is the most frequent in patients with traumatic brain injury with diffuse lesions. The intracranial pressure-cytokines correlation coefficients for the 16 patients varied substantially: interleukin-1β-intracranial pressure (-0.76 to 0.63); interleukin-6-intracranial pressure (-0.83 to 0.78); interleukin-8-intracranial pressure (-0.86 to 0.84); and interleukin-10-intracranial pressure (-0.36 to 0.65). The brain tissue oxygenation-cytokine correlation coefficients, like with intracranial pressure, also varied between patients: interleukin-1β-brain tissue oxygenation (-0.49 to 0.68), interleukin-6-brain tissue oxygenation (-0.99 to 0.84); interleukin-8-brain tissue oxygenation (-0.65 to 0.74); and interleukin-10-brain tissue oxygenation (-0.34 to 0.52). Similarly, we found no difference in the cytokine values inpatient microdialysis with and without swelling in the computed tomographic scan.. No clear relationship was found between the temporal pattern of cytokines and the behavior of the intracranial pressure, brain tissue oxygenation, and the presence or absence of swelling in the computed tomography scan. This study demonstrates the feasibility of microdialysis in recovering cytokines for a prolonged time, although there may be some nonresolved methodologic problems with this technique when we try to study the inflammation during traumatic brain injury that could affect the results and make interpretation of microdialysis data prone to difficulties.

Topics: Adolescent; Adult; Aged; Brain; Brain Chemistry; Brain Injuries; Cytokines; Female; Humans; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Intracranial Pressure; Male; Microdialysis; Middle Aged; Oxidation-Reduction; Prospective Studies; Tumor Necrosis Factor-alpha; Young Adult

To explore the dynamic changes of serum interleukin-6 (IL-6) and IL-8 in acute traumatic brain injury (TBI) and their correlations to the severity of brain injury and the condition of the patients.. Thirty-four patients with acute TBI were divided into two groups according to the Glasgow Coma Scale (GCS) score, clinical manifestations and the imaging data, namely patients with GCS score < or = 8 and those with GCS score between 9 and 12. Radioimmunoassay was employed to determine the serum levels of IL-6 and IL-8 at 6 different time points within 15 days after the injury in the two groups.. The serum IL-6 reached the peak level on the second day after the injury in patients with GCS score < or = 8 and on the 7th day in patients with GCS score of 9-12, showing significant differences in IL-6 variations between the two groups (P=0.046). The peak serum level of IL-8 occurred on the 7th day in patients with GCS score < or = 8 and on the 3rd day in patients with GCS score of 9-12, also showing significant differences (P=0.045). The peak level of IL-6 on the second day after the injury was significantly higher than the peak level of IL-8 that occurred on the 7th day, demonstrating significant differences in the variations of IL-6 and IL-8 after the injury (P=0.000).. The changes of serum IL-6 and IL-8 levels show positive correlations to the severity of the condition of the patients sustaining TBI. IL-6 variation is more obvious than that of IL-8 without intimate correlations between them. Clinically, serum IL-6 level can be more informative than serum IL-8 level in evaluating the changes of the condition of the TBI patients in early stage following the injury.

Topics: Acute Disease; Adolescent; Adult; Brain Injuries; Child; Female; Glasgow Coma Scale; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Trauma Severity Indices; Young Adult

Cerebral contusions contain numerous leukocytes, and a temporal relationship exists among cerebral chemokine expression, leukocyte recruitment, and contusion enlargement. This would suggest a role for chemokines in contusion development. However, it has not been established if serum concentrations of chemokines such as interleukin-8 (IL-8) or monocyte chemoattractant protein-1 (MCP-1) change with contusion enlargement.. Eighteen adult patients with severe contusional traumatic brain injury, on computerized tomography, were identified. Patients with diffuse injuries or extradural and subdural hematomas associated with mass effect were not included in the study. Daily serum samples were taken for the measurement of IL-8 and MCP-1 concentrations for up to 11 days postinjury.. In the patients who died while in intensive care, IL-8 and MCP-1 were significantly greater than in those patients discharged (18 [0-202] vs. 0 [0-156] pg/mL and 498 [339-1,063] vs. 368 [86-11,289] pg/mL for IL-8 and MCP-1, respectively). No difference was seen in serum chemokine levels in patients who deteriorated with contusion enlargement compared with those that did not. The IL-8 and MCP-1 concentrations did not change significantly over time either in the group as a whole or in the subgroup of patients who deteriorated.. These inflammatory mediators may be predictive of a poor outcome in patients with traumatic brain injury in which contusions are the predominant abnormality. However, they do not distinguish those patients who will deteriorate because of contusion enlargement.

Topics: Adult; Aged; Brain Injuries; Chemokine CCL2; Disease Progression; Female; Humans; Interleukin-8; Male; Middle Aged; Young Adult

The aim of this work was to verify neuroprotective and anti-inflammatory properties of FBD, a herbal formula composed of Poria cocos, Atractylodes macrocephala and Angelica sinensis, in ICR mice subjected to repetitive 10 min of common carotid arteries occlusion followed 24 h reperfusion. Intragastrical pretreatment with supercritical carbon dioxide extract (FBD-CO(2), 37.5 mg/kg) twice daily for 3.5 d, significantly reduced Evans Blue influx, neuron specific enolase (NSE) efflux, brain infarction (all p<0.05), also inhibited polymorphonuclear leukocytes (PMNs) infiltration (p<0.001), suppressed secretion of tumor necrosis factor (TNF)-alpha in blood (p<0.05), interleukin (IL)-1beta and IL-8 in brain (both p<0.01), and down-regulated cerebral expression of phosphor-IkappaB-alpha and phosphor-nuclear factor kappa-B (NF-kappaB), whether coupled with aqueous extract (FBD-H(2)O, 150 mg/kg) or not. Moreover, FBD-CO(2) (0.1-10 microg/ml) inhibited 0.1 microM phorbol myristate acetate-evoked oxidative burst in rat PMNs, 20 ng/ml TNF-alpha-triggered PMNs adhesion to ECV304 endothelial cells, and PMNs neurotoxicity to PC12 neuron-like cells as well as NSE release (IC(50) 1.30, 0.98, 0.24 and 0.82 microg/ml, respectively). Our study demonstrated that FBD-CO(2) prevented brain ischemia/reperfusion injury, at least in part, by limiting PMNs infiltration and neurotoxicity mediated by TNF-alpha, IL-1beta and IL-8, via inhibition on NF-kappaB activation.

Topics: Angelica sinensis; Animals; Atractylodes; Brain Injuries; Brain Ischemia; Disease Models, Animal; Drugs, Chinese Herbal; Inflammation; Interleukin-1beta; Interleukin-8; Male; Mice; Mice, Inbred ICR; Neuroprotective Agents; Neutrophil Infiltration; NF-kappa B; Polyporales; Reperfusion Injury; Tumor Necrosis Factor-alpha

Because of complex pathophysiology and severe consequences, traumatic brain injuries (TBI) are an important medical problem. Pathophysiology of TBI includes local and systemic stress response, in which interleukin-8 (IL-8) is considered as a key mediator of neuroinflammation. However, prognostic relevance of IL-8 measurement in adult patients with severe TBI is not certain. Therefore, IL-8 was determined in blood samples from central venous and jugular bulb catheter and in cerebrospinal fluid of twenty patients with isolated TBI at admission to Intensive Care Unit. None of the patients had history of stroke, dementia, autoimmune diseases, acute infection or medication with anti-inflammatory drugs. Ten patients died due to traumatic brain injury, while the other ten recovered well. While there was no significant difference of IL-8 levels in cerebrospinal fluid between survivors and nonsurvivors, central venous plasma level of IL-8 was significantly lower in survivors (71.00 +/- 14.17 pg/ml), than in nonsurvivors (111.26 +/- 16.9 pg/ml). Receiver Operating Characteristic (ROC) analysis revealed significant prognostic value for IL-8 in the blood as well as for the age of patients, Glasgow Coma Scale (GCS) and Acute Physiologic and Chronic Health Evaluation (APACHE II). These findings suggest that the central venous plasma values of IL-8 at admission might be an early predictive marker in patients with severe TBI, comparative to standard clinical prognostic markers such as APACHE II and GCS.

Topics: Adult; APACHE; Biomarkers; Brain Injuries; Female; Glasgow Coma Scale; Humans; Interleukin-8; Male; Middle Aged; Prognosis; ROC Curve

Foetal inflammation is associated with an increased risk of brain damage in preterm infants whereas IGF-I is essential for cerebral development and exhibits anti-apoptotic properties.. To assess levels of IGF-I and IGF binding proteins at very preterm birth and to evaluate their relationship with foetal pro-inflammation and cerebral damage.. Levels of IGF-I, IGF binding protein 3 (IGFBP-3), high- (hp) and low-phosphorylated (lp) IGFBP-1 in cord blood and neonatal blood at 72 h after delivery were analysed in relation to levels of cytokines and cerebral damage as detected by ultrasound in 74 inborn infants [mean gestational age (GA) 27.1 weeks]. Evaluation was performed separately according to birth weight for GA.. In cord blood of infants appropriate for gestational age (AGA) higher levels of IL-6 and IL-8 were associated with lower IGF-I (r =-0.38, p = 0.008 and r =-0.36, p = 0.014). Higher levels of IL-6, IL-8 and TNF-alpha were associated with both higher levels of lpIGFBP-1 (r = 0.54, p < 0.001, r = 0.50, p < 0.001 and r = 0.13, p = 0.012, respectively) and hpIGFBP-1 (r = 0.55, p < 0.001, r = 0.45, p = 0.002 and r = 0.32, p = 0.026, respectively). Infants with intraventricular haemorrhage grade III (n = 5) had higher levels of lp/hpIGFBP-1 in cord blood (p = 0.001 and 0.002, respectively).. Pro-inflammation at birth is associated with changes in the IGF-system. This may be of importance for development of brain damage in preterm infants.

Topics: Biomarkers; Brain; Brain Injuries; Fetal Blood; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Infant, Small for Gestational Age; Inflammation; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Interleukin-6; Interleukin-8; Linear Models; Prospective Studies

Traumatic brain injury (TBI) acts as an inducer of the inflammatory reaction expressed by the release of pro-inflammatory cytokines (interleukin-1beta [IL-1beta], interleukin-6 [IL-6] and interleukin-8 [IL-8]), and causes metabolic alterations in the early, post-traumatic state, either in the brain or/and the systemic circulation. The metabolic changes involve carbohydrates, proteins and lipids. We focused on the serum lipid profile, the impact of trauma on lipoproteins, and their subsequent effects, on inflammation. We investigated the role of cytokines and serum lipids, in patient outcome, reviewing 30-day mortality and the Glasgow Coma Scale (GCS). A total of 75 patients with severe or moderate TBI (GCS

Topics: Adolescent; Adult; Aged; Brain Injuries; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Glasgow Coma Scale; Humans; Hypolipoproteinemias; Inflammation; Interleukin-6; Interleukin-8; Male; Middle Aged

Previous studies have shown that labile zinc and inflammatory mediators participate in many pathophysiological processes. The present study investigated the effects of traumatic brain injury (TBI) on the levels of labile zinc and certain proinflammatory factors in rat lung. Male Wistar rats were randomly assigned to 7 groups as follows: normal group, group with sham operation, and TBI groups that were sacrificed respectively at 1, 6, 24, and 72 hr, and on day 7 post-injury. Pulmonary labile zinc, tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-8, and wet/dry weight ratio were measured at the specified time intervals. TBI caused a gradual increase of pulmonary labile zinc as demonstrated by fluorescence staining with Zinpyr-4 (ZP4). The levels of TNF-alpha and IL-8 and the lung wet/dry weight ratios were higher in the TBI groups compared to the normal and sham-operated groups (p <0.05). There were highly positive correlations between the intensity of ZP4 fluorescence and the pulmonary levels of TNF-alpha and IL-8. The results suggest that TBI induces rapid increases of labile zinc and inflammatory mediators in lung, which may participate in the pathogenesis of acute lung injury.

Topics: Animals; Brain Injuries; Cytokines; Disease Progression; Fluorescent Dyes; Homeostasis; Interleukin-8; Lung; Male; Organ Size; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha; Up-Regulation; Zinc

Ischemia and systemic infection are implicated in the etiology of periventricular white matter injury, a major cause of adverse motor and cognitive outcome in preterm infants. Cytokines are signaling proteins that can be produced as part of the inflammatory response to both ischemia and infection. The aim of this study was to relate cerebrospinal fluid (CSF) concentrations of IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma) to magnetic resonance-defined white matter injury in preterm infants. Relationships between CSF and plasma cytokine concentrations were also examined. Preterm infants (

Topics: Brain; Brain Injuries; Cytokines; Humans; Infant; Infant, Newborn; Infant, Premature; Interferon-gamma; Interleukin-10; Interleukin-6; Interleukin-8; Magnetic Resonance Imaging; Signal Transduction; Transforming Growth Factor alpha

To investigate the role of apoptosis of pulmonary cells in aspiration induced lung injury in patients with severe brain injury with or without aspiration-induced lung injury.. The Glasgow scale (GCS) of 11 dead patients with severe closed brain injury was 3-8. There 11 cases were divided into aspiration-induced lung injury (AILI) and non-aspiration-induced lung injury (NAILI) groups. The plasma levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) were measured, and the ratio of apoptosis in lung tissue cells was also determined.. The plasma levels of TNF-alpha and IL-8 in NAILI and AILI groups were (2.17+/-0.41)nug/L vs. (3.14+/-0.28)nug/L and (0.42+/-0.05)nug/L vs. (0.91+/-0.08) nug/L (P<0.05) respectively. Lung tissue cell apoptosis ratio was significantly higher in AILI group than NAILI group (P<0.01).. TNF-alpha and IL-8 may induce apoptosis in lung tissues through different signaling pathway. During the early phase of aspiration-induced lung injury complicating severe closed brain injury, apoptosis in cells of lung tissue may play a role in the pathogenes.

Topics: Adult; Apoptosis; Autopsy; Brain Injuries; Female; Humans; In Situ Nick-End Labeling; Interleukin-8; Lung; Male; Pneumonia, Aspiration; Respiratory Distress Syndrome; Tumor Necrosis Factor-alpha

S100B protein (S100B) has been described as a marker of brain injury. Various cytokines also increase in the cerebrospinal fluid (CSF) of patients with severe traumatic brain injury (TBI). Thus, we investigated early changes in the concentrations of CSF S100B and various cytokines after TBI and evaluated the relations of both S100B and cytokines to intracranial pressure (ICP) and prognosis. Twenty-three patients with severe TBI and a Glasgow Coma Scale score of 8 or less on admission were included in this study. CSF and serum samples were obtained on admission and at 6, 12, 24, 48, 72, and 96 h after injury. CSF concentrations of S100B and CSF and serum concentrations of five cytokines (IL-1beta, TNF-alpha, IL-6, IL-8, and IL-10) were measured and compared. The CSF S100B concentration was increased for 6 h after injury and decreased thereafter. The CSF concentrations of IL-6 and IL-8 peaked within 6 h after injury; other cytokines (IL-1beta, TNF-alpha, and IL-10) were elevated for 24 h after injury and gradually decreased thereafter. Peak CSF S100B concentrations correlated significantly with ICP determined at the time CSF samples were taken (r = 0.729, P < 0.0001). For the cytokines investigated, only the peak CSF IL-1beta concentration correlated significantly and positively with the peak CSF S100B concentration (r = 0.397, P < 0.005). Peak CSF concentrations of S100B (1649 +/- 415 microg/L, mean +/- SEM) and IL-1beta (16.5 +/- 3.3 pg/mL) in the 6 patients with high ICP were significantly higher than those (233 +/- 67 microg/L, 7.6 +/- 1.7 pg/mL, respectively) in the 17 patients with low ICP (P < 0.05). The CSF S100B concentration (1231 +/- 378 microg/L) in eight patients with an unfavorable outcome was significantly higher than that (267 +/- 108 microg/L) in 15 patients with a favorable outcome (P < 0.05). The CSF IL-1beta concentration (14.8 +/- 3.4 pg/mL) in eight patients with an unfavorable outcome tended to be higher than that (7.3 +/- 1.5 pg/mL) in 15 patients with a favorable outcome (P = 0.057). CSF concentrations of S100B and cytokines peak within 24 h after severe TBI and decrease gradually thereafter. CSF S100B and IL-1beta may be useful as predictors of outcome in cases of severe TBI.

Topics: Adult; Brain Injuries; Cytokines; Female; Glasgow Coma Scale; Humans; Interleukin-1; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Nerve Growth Factors; Pressure; Prognosis; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Tumor Necrosis Factor-alpha

The subjects were 22 patients with severe head injury. The average age was 45 +/- 18.3 years. There were 13 survivors and 9 fatalities. Samples of peripheral blood and cerebrospinal fluid (CSF) were taken four times, at the time of admission and at 24, 72, and 168 hours later. IL-6: For the survivor group, peripheral blood levels were 181, 105, 37, and 26 pg/ml, respectively (median values). CSF levels were 5376, 3565, 328, and 764 pg/ml, respectively. For the fatality group, peripheral blood levels were 102, 176, 873, and 3059 pg/ml, respectively, whereas CSF levels were 15241, 97384, 548225, and 366500 pg/ml, respectively. IL-8: For the survivor group, peripheral blood levels were 36, 15, 15, and 15 pg/ml, respectively, whereas CSF levels were 23736, 4074, 355, and 1509 pg/ml, respectively. For the fatality group, peripheral blood levels were 21, 28, 43, and 77 pg/mL, respectively, whereas CSF levels were 29003, 8906, 5852, and 8220 pg/ml, respectively. IL-6 and IL-8 levels were significantly higher after 72 hours in the fatality group. The fact that CSF IL-8 was 1000 times that in the peripheral blood at the time of admission, and decreased thereafter, indicates that IL-8 is a key mediator of neuroinflammation.

Topics: Adult; Brain Injuries; Encephalitis; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged

To compare S-100B and interleukin-8 serum values on scene/at admission and 12 hrs later with respect to neurologic long-term outcome 12 months after cardiac arrest and return of spontaneous circulation, as well as after severe traumatic brain injury.. Prospective comparative cohort study.. On scene; intensive care units of a university hospital.. Twenty patients with out-of-hospital cardiac arrest. Twenty patients with severe traumatic brain injury.. Therapy was adjusted to the standards of modern prehospital and intensive care management by physicians who were not involved in the study.. First median S-100B values of the cardiac arrest group (4.42 ng/mL) mounted as high as those of the traumatic brain injury group (4.11 ng/mL). Within 12 hrs, S-100B levels significantly decreased to 0.75 ng/mL in cardiac arrest patients and to 0.68 ng/mL in traumatic brain injury patients but remained significantly elevated compared with the controls (0.04 ng/mL). Interleukin-8 levels of the cardiac arrest patients on scene (30.33 pg/mL) were clearly elevated above normal (12.60 pg/mL) and increased significantly to 101.40 pg/mL after 12 hrs. They showed no significant difference compared with those of the traumatic brain injury patients (78.75 pg/mL and 96.00 pg/mL, respectively). Multivariate Cox regression analysis in cardiac arrest patients identified only the S-100B level measured 12 hrs after study entry as an independent predictor for unfavorable neurologic outcome according to the Glasgow Outcome Scale score. In contrast, S-100B as well as interleukin-8 levels quantified 12 hrs after admission significantly predicted an unfavorable neurologic course in the traumatic brain injury group.. Significantly elevated S-100B and interleukin-8 serum levels 12 hrs after cardiac arrest suggest that primary brain damage and systemic inflammatory response are comparably serious with that of traumatic brain injury. In both collectives, increased S-100B values measured 12 hrs after insult correlated well with an unfavorable neurologic outcome after 12 months.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Brain Injuries; Case-Control Studies; Female; Germany; Glasgow Outcome Scale; Heart Arrest; Humans; Interleukin-8; Logistic Models; Male; Middle Aged; Multivariate Analysis; Nerve Growth Factors; Prospective Studies; ROC Curve; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Sensitivity and Specificity; Treatment Outcome

Topics: Biomarkers; Brain Injuries; Humans; Interleukin-8; Nerve Growth Factors; S100 Calcium Binding Protein beta Subunit; S100 Proteins

Traumatic brain injury (TBI) is characterized by a high mortality which is largely determined by the initial cerebral trauma, secondary brain injury or indirectly during a Multiple Organ Dysfunction Syndrome (MODS). Therefore, we analyzed IL-6, IL-8, and IL-10 in cerebrospinal fluid (CSF) and in plasma with respect to blood-brain barrier (BBB) integrity in 29 patients suffering from isolated TBI. IL-6 and IL-8 were significantly increased compared to baseline levels early after trauma in CSF and plasma. In all patients CSF IL-6 and IL-8 were found to be higher than corresponding plasma levels. IL-10 in plasma was significantly increased above control plasma values, however, without a significant difference to the corresponding CSF values. BBB dysfunction was temporary present in 23 patients. Significant correlations between BBB dysfunction and cytokines were not found. Thus, alterations of the BBB seems not to influence the distribution pattern of interleukines in CSF and plasma after trauma.

Topics: Adolescent; Adult; Aged; Biomarkers; Blood-Brain Barrier; Brain Injuries; Female; Glasgow Coma Scale; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Regression Analysis; Survival Rate; Time Factors; Treatment Outcome

The cerebral blood flow velocity (CBVF) was measured by transcranial Doppler sonography in patients with severe traumatic brain injury (TBI) in order to determine, whether it depends on the posttraumatic inflammatory response.. CBVF in both middle cerebral arteries (MCA) was recorded in 25 comatous TBI patients (male 20; female five; mean age +/- standard deviation (S.D.), 41 +/- 20 years) and correlated to the levels of interleukine-(IL) 6, IL-8 and IL-10 in corresponding CSF/plasma samples, to PaCO2 and to intracranial (ICP), mean arterial (MAP) and cranial perfusion pressure (CPP).. CSF IL-6 and IL-8 were clearly higher than the corresponding plasma levels (mean CSF/plasma quotient for IL-6: 159 +/- 582; for IL-8: 143 +/- 311). CBVF did not show large side-to-side differences at each examination indicating that CBFV in both MCAs was determined mostly by systemic conditions and not by severe regional abnormalities. Since all other evaluated variables including interleukines represent also systemic conditions we used the mean value (MCBFV) of both CBFVs for analysis. By stepwise regression analysis between MCBVF (mean +/- S.D., 80 +/- 26 cm/s) and the variables PaCO2 (33 +/- 4 mmHg), MAP (86 +/- 12 mmHg), ICP (20 +/- 11 mmHg), CPP (70 +/- 14 mmHg) and CSF or plasma IL-6, IL-8 and IL-10, it turned out that MCBFV correlated significantly with PaCO2 (r = 0.478; P < 0.01) and CSF IL-8 (r = -0.361; P < 0.05).. When CPP is adequate for brain perfusion, CBFV in large brain supplying arteries depends predominantly on PaCO2 and shows only a slight association to intrathecal IL-8 levels. For clinical interpretation of CBFV data, the inflammatory response seems to be of minor relevance.

Topics: Adult; Blood Flow Velocity; Blood Pressure; Brain Injuries; Cerebrovascular Circulation; Female; Humans; Inflammation Mediators; Interleukin-10; Interleukin-6; Interleukin-8; Interleukins; Intracranial Pressure; Male; Middle Cerebral Artery; Ultrasonography, Doppler, Transcranial

The increased risk for Alzheimer's Disease (AD) associated with traumatic brain injury (TBI) suggests that environmental insults may influence the development of this age-related dementia. Recently, we have shown that the levels of the beta-amyloid peptide (A beta 1-42) increase in the cerebrospinal fluid (CSF) of patients after severe brain injury and remain elevated for some time after the initial event. The relationships of elevated A beta with markers of blood-brain barrier (BBB) disruption, inflammation, and nerve cell or axonal injury were evaluated in CSF samples taken daily from TBI patients. This analysis reveals that the rise in A beta 1-42 is best correlated with possible markers of neuronal or axonal injury, the cytoskeletal protein tau, neuron-specific enolase (NSE), and apolipoprotein E (ApoE). Similar or better correlations were observed between A beta 1-40 and the three aforementioned markers. These results imply that the degree of brain injury may play a decisive role in determining the levels of A beta 1-42 and A beta 1-40 in the CSF of TBI patients. Inflammation and alterations in BBB may play lesser, but nonetheless significant, roles in determining the A beta level in CSF after brain injury.

Topics: Acute-Phase Proteins; Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Biomarkers; Blood-Brain Barrier; Brain Injuries; Cohort Studies; Cytokines; Humans; Interleukin-6; Interleukin-8; Peptide Fragments; Phosphopyruvate Hydratase; Risk Factors; tau Proteins; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

Ischemic cerebral injury follows a well-attested sequence of events, including 3 phases: depolarization, biochemical cascade, and reperfusion injury. Leukocyte infiltration and cytokine-mediated inflammatory reaction are known to play a pivotal role in the reperfusion phase. These events exacerbate the brain injury by impairing the normal microvascular perfusion and through the release of cytotoxic enzymes. The aim of the present study was to determine whether a leukocyte-depleting filter (LeukoGuard LG6, Pall Biomedical, Portsmouth, United Kingdom) could improve the cerebral outcome after hypothermic circulatory arrest.. Twenty pigs (23-30 kg) were randomly assigned to undergo cardiopulmonary bypass with or without a leukocyte-depleting filter before and after a 75-minute period of hypothermic circulatory arrest at 20 degrees C. Electroencephalographic recovery, S-100beta protein levels, and cytokine levels (interleukin 1beta, interleukin 8, and tumor necrosis factor alpha) were recorded up to the first postoperative day. Postoperatively, all animals were evaluated daily until death or until electively being put to death on day 7 by using a quantitative behavioral score. A postmortem histologic analysis of the brain was carried out on all animals.. The rate of mortality was 2 of 10 in the leukocyte-depletion group and 5 of 10 in control animals. The risk for early death in control animals was 2.5 (95% confidence interval, 0.63-10.0) times higher than that of the leukocyte-depleted animals. The median behavioral score at day 7 was higher in the leukocyte-depletion group (8.5 vs 3.5; P =.04). The median of total histopathologic score was 8.5 in the leukocyte-depletion group and 15.5 in the control group (P =.005).. A leukocyte-depleting filter improves brain protection after a prolonged period of hypothermic circulatory arrest.

Topics: Animals; Brain Injuries; Calcium-Binding Proteins; Chronic Disease; Disease Models, Animal; Electroencephalography; Female; Heart Arrest, Induced; Hemofiltration; Hypothermia, Induced; Inflammation; Interleukin-1; Interleukin-8; Leukocyte Count; Leukocytes; Morbidity; Nerve Growth Factors; Random Allocation; Reperfusion Injury; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Severity of Illness Index; Swine; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha

A profound inflammatory response is initiated immediately following traumatic brain injury (TBI) and is characterized by the release of several cytokines with pro- and anti-inflammatory functions. In order to elucidate which cytokines are released in the human brain in response to injury as well as in the peripheral compartment, IL-1, IL-6, IL-8, IL-10, TNF-alpha and TGF-beta were monitored in CSF and serum of severely brain-injured patients. Furthermore, we investigated the possible modulation of systemic reactions by IL-6 and the ability of IL-6 and IL-8 to promote the synthesis of nerve growth factor.

Topics: Animals; Blood-Brain Barrier; Brain Damage, Chronic; Brain Injuries; Cells, Cultured; Cytokines; Gene Expression Regulation; Humans; Inflammation; Interleukin-6; Interleukin-8; Mice; Nerve Growth Factors; Rats

Interleukin (IL) 8 was measured in CSF of 14 patients with severe traumatic brain injury. IL-8 levels were significantly higher in CSF (up to 8,000 pg/ml) than serum (up to 2,400 pg/ml) (p < 0.05), suggesting intrathecal production. Maximal IL-8 values in CSF correlated with a severe dysfunction of the blood-brain barrier. Nerve growth factor (NGF) was detected in CSF of 7 of 14 patients (range of maximal NGF: 62-12,130 pg/ml). IL-8 concentrations were significantly higher in these patients than in those without NGF (p < 0.01). CSF containing high IL-8 (3,800-7,900 pg/ml) induced greater NGF production in cultured astrocytes (202-434 pg/ml) than samples with low IL-8 (600-1,000 pg/ml), which showed a smaller NGF increase (0-165 pg/ml). Anti-IL-8 antibodies strongly reduced (52-100%) the release of NGF in the group of high IL-8, whereas in the group with low IL-8, this effect was lower (0-52%). The inability of anti-IL-8 antibodies to inhibit the synthesis of NGF completely may depend on cytokines like tumor necrosis factor alpha and IL-6 found in these CSF samples, which may act in association with IL-8. Thus, IL-8 may represent a pivotal cytokine in the pathology of brain injury.

Topics: Adolescent; Adult; Aged; Animals; Astrocytes; Blood-Brain Barrier; Brain Injuries; Cells, Cultured; Cerebrospinal Fluid Proteins; Female; Gene Expression Regulation; Humans; Interleukin-8; Male; Mice; Middle Aged; Nerve Growth Factors; Recombinant Proteins

After acute brain injury there may be increased intracranial production of cytokines, with activation of inflammatory cascades. We have sought to determine if a transcranial cytokine gradient was demonstrable in paired sera of 32 patients requiring intensive care after acute brain injury. The difference between concentrations of IL-1 beta, IL-6, IL-8 and TNF alpha in jugular venous and arterial serum was measured on admission, and at 24, 48 and 96 h after the primary injury. There were no differences in IL-1 beta, IL-8 or TNF alpha, but median gradients of 6.7 and 11.5 pg ml-1 for IL-6 were demonstrated in the traumatic brain injury (n = 22) and subarachnoid haemorrhage (n = 10) groups, respectively (normal values in serum < 4.7 pg ml-1; P < 0.001 both groups). This suggests that there is significant production of IL-6 by intracranial cells after acute brain injury. Therapy directed towards combatting the negative effects of IL-6 may potentially benefit patients who have sustained an acute brain injury.

Topics: Acute Disease; Adolescent; Adult; Aged; Brain; Brain Injuries; Critical Care; Cytokines; Female; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Jugular Veins; Male; Middle Aged; Subarachnoid Hemorrhage; Tumor Necrosis Factor-alpha

To examine the kinetics of plasma tumor necrosis factor alpha (TNF alpha), interleukin-6 (IL-6) and interleukin-8 (IL-8) in patients with severe trauma and to discuss their relationship with organ damage and endotoxemia.. Seventeen patients (10 men and 7 women) with severe trauma were selected in this study. Their mean age was 37.9 +/- 11.9 years. All patients were divided into two groups according to injury severity score (ISS): group I with ISS from 16-25 (18.8 +/- 2.9, n = 10) and group II with ISS more than 25 (34.3 +/- 8.3, n = 7). Ten young healthy volunteers (6 men and 4 women) were used as controls. Plasma TNF alpha and IL-8 levels were assayed with enzyme-linked immunosorbent assay. IL-6 activity in the plasma was determined by bioassay with IL-6-dependent cell-line 7TD1. Limulus amebocyte lysate chromogenic test was used for plasma endotoxin assay.. Plasma cytokine levels in patients with trauma had a successively significant increase. Plasma TNF level increased earlier. Increases in plasma IL-6 and IL-8 occurred later. All the increases were significantly correlated with the severity of trauma and organ damage after trauma. In addition, obvious endotoxemia occurred at the early stage of trauma and was significantly correlated with the severity of trauma and the levels of plasma TNF alpha, IL-6 and IL-8.. Release of TNF alpha, IL-6 and IL-8 can be significantly increased in patients with severe trauma. The increase may be related to massive endotoxin translocation and may play an important role in the development of organ damage after trauma.

Topics: Adolescent; Adult; Aged; Brain Injuries; Endotoxemia; Female; Fractures, Bone; Humans; Injury Severity Score; Interleukin-6; Interleukin-8; Liver; Male; Middle Aged; Pelvic Bones; Tumor Necrosis Factor-alpha