BACKGROUND AND PURPOSE: A few groups have suggested that activated cytokines and nitrosative stress are closely involved in the pathogenesis of different demyelinating disorders induced by the neuroinflammatory destruction of neurons. The purpose of this study was to elucidate the associations of cytokines and S-nitrosothiols (RSNO) with the severity of neurodegeneration during relapse in demyelinating disorders of the central nervous system. METHODS: We measured levels of interleukin-6 (IL-6), erythropoietin, RSNO, and phosphorylated neurofilament heavy chain (pNfh) in cerebrospinal fluid (CSF) samples obtained from patients with different demyelinating disorders: multiple sclerosis (MS, n=52), acute disseminated encephalomyelitis (ADEM, n=9), and neuromyelitis optica spectrum disorders (NMOSD) with aquaporin-4 immunoglobulin G (AQP4-IgG, n=12). We compared these levels with those measured in a control group (n=24). RESULTS: We found that IL-6 in CSF was elevated in NMOSD with AQP4-IgG and ADEM patients as well as in MS patients after the destruction of soluble IL-6. Erythropoietin levels were lower in MS, while RSNO levels were higher in NMOSD with AQP4-IgG and MS patients than in the control group. CSF pNfh levels were elevated in MS and ADEM patients. CONCLUSIONS: These results confirm that IL-6 is activated in different demyelinating disorders, with this elevation being more prominent in the CSF of NMOSD with AQP4-IgG and ADEM patients. Moreover, S-nitrosylation is activated in demyelinating disorders with spinal-cord injury and neurodegeneration in these patients. However, we found no correlation between these biochemical markers, and so we could not confirm whether IL-6-mediated nitric oxide production is involved in spinal-cord lesions.
Biomarkers ; Central Nervous System* ; Cerebrospinal Fluid ; Cytokines ; Demyelinating Diseases* ; Encephalomyelitis, Acute Disseminated ; Erythropoietin ; Humans ; Immunoglobulin G ; Interleukin-6* ; Intermediate Filaments ; Multiple Sclerosis ; Neuromyelitis Optica ; Neurons ; Nitric Oxide ; Recurrence ; S-Nitrosothiols*

OBJECTIVE: Magnetic resonance imaging (MRI) of chronic subdural hematoma (CSDH) detects various patterns, which can be attributed to many factors. The purpose of this study was to measure the level of interleukin-6 (IL-6), interleukin-8 (IL-8), and highly specific protein [beta-trace protein (betaTP)] for cerebrospinal fluid (CSF) in CSDHs, and correlate the levels of these markers with the MRI findings. METHODS: Thirty one patients, treated surgically for CSDH, were divided on the basis of MRI findings into hyperintense and non-hyperintense groups. The concentrations of IL-6, IL-8, and betaTP in the subdural fluid and serum were measured. The betaTP was considered to indicate an admixture of CSF to the subdural fluid if betaTP in the subdural fluid (betaTP(SF))/betaTP in the serum (betaTP(SER))>2. RESULTS: The mean concentrations of IL-6 and IL-8 of the hyperintense group (n=17) of T1-WI MRI were 3975.1+/-1040.8 pg/mL and 6873.2+/-6365.4 pg/mL, whereas them of the non-hyperintense group (n=14) were 2173.5+/-1042.1 pg/mL and 2851.2+/-6267.5 pg/mL (p<0.001 and p=0.004). The mean concentrations of betaTP(SF) and the ratio of betaTP(SF)/betaTP(SER) of the hyperintense group (n=13) of T2-WI MRI were 7.3+/-2.9 mg/L and 12.6+/-5.4, whereas them of the non-hyperintense group (n=18) were 4.3+/-2.3 mg/L and 7.5+/-3.9 (p=0.011 and p=0.011). CONCLUSION: The hyperintense group on T1-WI MRI of CSDHs exhibited higher concentrations of IL-6 and IL-8 than non-hyperintense group. And, the hyperintese group on T2-WI MRI exhibited higher concentrations of betaTP(SF) and the ratio of betaTP(SF)/betaTP(SER) than non-hyperintense group. These findings appear to be associated with rebleeding and CSF admixture in the CSDHs.
Cerebrospinal Fluid ; Cytokines* ; Hematoma, Subdural, Chronic* ; Humans ; Interleukin-6 ; Interleukin-8 ; Interleukins ; Magnetic Resonance Imaging* ; Prospective Studies*

PURPOSE: Cytokines play important roles on the expression of various neuronal inflammatory disease and insults. The purpose of this study was to evaluate the levels of interleukine (IL)-6, IL-8, IL-10 in cerebrospinal fluid (CSF) in children with aseptic meningitis and compare them with those of the patients having other acute neurological symptoms. METHODS: We retrospectively reviewed the medical records of the children who admitted in the pediatric department of Hanyang University Guri Hospital for acute neurological symptoms and had CSF examinations from September 2012 to July 2013. We classified them into six groups as acute encephalopathy, epilepsy, febrile convulsion, headache, infantile fever, and meningitis. We analyzed the clinical and laboratory data from them. RESULTS: A total of 87 CSFs of the patients were available. The levels of CSF IL-6, IL-8, and IL-10 were significantly increased in the group with aseptic meningitis group as compared to the other groups (P<0.05). CSF IL-6 (r=0.576, P=0.000), IL-8 (r=0.329, P=0.003), and IL-10 (r=0.523, P=0.000) were all significantly correlated with CSF White bood cell (WBC) count. Among the patients with aseptic meningitis, CSF enterovirus positive patients (CSF entero+) showed significantly increased IL-6, IL-8, IL-10 levels than CSF enterovirus negative patients (CSF entero-) (P<0.05). In addition, the CSF entero+ and the increase of IL-10 were significantly correlated (x2=6.827, P=0.033). CONCLUSION: In patients with aseptic meningitis, the CSF IL-6, IL-8 and IL-10 were more expressed than in other neurological disease group. Among them, the enteroviral meningitis may be more related with IL-6, IL-8 and IL-10 expression than in other causes of aseptic meningitis.
Cerebrospinal Fluid* ; Child* ; Cytokines ; Enterovirus ; Epilepsy ; Fever ; Headache ; Humans ; Interleukin-10 ; Interleukin-6 ; Interleukin-8 ; Interleukins ; Medical Records ; Meningitis ; Meningitis, Aseptic* ; Neurons ; Retrospective Studies ; Seizures, Febrile

OBJECTIVETo evaluate the clinical efficacy of two brain protective methods for aortic operation according to S100beta protein (S100beta) and interleukin-6 (IL-6) in cerebrospinal fluid (CSF).

METHODSFrom November 2004 to April 2005, 14 patients who underwent aortic operations with circulatory arrest were alternatively allocated to one of two methods of brain protection: only deep hypothermic circulatory arrest (core temperature, 18 degrees C) for descending thoracic aorta operations (group DHCA, n = 5) or selective antegrade cerebral perfusion (core temperature, 20 degrees C; flow rate, 10 ml kg(-1) min(-1)) for aortic arch operations with DHCA (group ASCP, n = 9). Indications for surgical intervention were Stanford type A dissection in 11 patients, Stanford type B dissection in 2 patients, false aneurysm on thoracoabdominal aorta in 1 patient. S100beta and IL-6 in CSF were assayed in all patients from each group before cardiopulmonary bypass, as well as 0, 6, 12, 24, 48, 72 h after the operation.

RESULTSThere were no significant differences in lowest core temperature (P > 0.05), hematocrit in lowest core temperature (P > 0.05) and the velocity of rewarming. Mean circulatory arrest time in ASCP group was significant longer than in DHCA group (P < 0.05). There were much more patients with jugular arteries impaired or accompanied with related cerebrovascular diseases in group ASCP compared to group DHCA. The baseline of S100beta in CSF before cardiopulmonary bypass was no difference. S100beta value in CSF ascended to peak level in 12 h after the operation, showing significantly higher in group DHCA than in group ASCP [DHCA vs. ASCP, (0.90 +/- 0.11) microg/ml vs. (0.61 +/- 0.26) pg/ml]. In most hours after operation there was significant intergroup difference. IL-6 value in CSF ascended to peak level in 12 h postoperative for group DHCA and 0 h postoperative for group ASCP. There was no significance difference observed in IL-6 of CSF between two groups except 6 h and 12 h postoperative.

CONCLUSIONSBrain ischemic injury occurred during aortic operations assisted by brain protective methods is not serious. Unilateral ASCP which can delivery adequate oxygen to brain during circulation arrest has some advantage of alleviating ischemic injury compared with only DHCA.

Adult ; Aortic Aneurysm ; cerebrospinal fluid ; surgery ; Brain ; blood supply ; Circulatory Arrest, Deep Hypothermia Induced ; methods ; Female ; Humans ; Interleukin-6 ; cerebrospinal fluid ; Male ; Middle Aged ; Nerve Growth Factors ; cerebrospinal fluid ; Perfusion ; Postoperative Period ; S100 Calcium Binding Protein beta Subunit ; S100 Proteins ; cerebrospinal fluid

PURPOSE: Preterm very low birth weight infant have high rate of adverse neurodevelopmental sequale. Recently, there have been lots of reports that human umbilical cord blood transplantation ameliorates functional deficits in animal models as hypoxic ischemic injury. This pilot study was undertaken to determine the clinical efficacy and safety of autologous umbilical cord blood cell transplantation for preventing neurodevelopmental sequale in perterm VLBW. METHODS: Subjects were 26 preterm infants whose birth weight are less than 1,500 g and delivered under the intrauterine period 34 weeks. Autologous umbilical mononuclear cells (about 5.87x10(7)/kg) were injected to neonate via the umbilical vein on the postnatal 24-48 hour. The therapeutic efficacy was assessed by numbers of nucleated RBC, urinary uric acid/creatinine ratio, concentration of neuron specific enolase (NSE), interleukin 6 (IL6), interleukin-1beta (IL-1beta), and glial cell derived neurotrophic factor (GDNF) in serum and cerebrospinal fluid on day 1 and 7. RESULTS: There were no significant differences in the numbers of the nucleated RBC, urinary uric acid/creatinine ratio, concentration of creatine kinase between the transplanted infants and controls. But the nucleated RBC is more likely to be rapidly discharged in the transplanted group. In the transplanted group, the concentrations of IL6, IL-1beta, and GDNF were no significant difference between day 1 and 7, although GDNF seemed to be elevated. Serum NSE concentration was significantly elevated after transplantation, but not in CSF. CONCLUSION: It is suggested that autologous umbilical cord blood transplantation in preterm very low birth weight infant is safe to apply clinical practice. Long term follow up study should be needed to evaluate the potential therapeutic effect of umbilical cord blood transplantation for neuroprotection.
Birth Weight ; Cell Transplantation ; Cerebrospinal Fluid ; Creatine Kinase ; Fetal Blood* ; Glial Cell Line-Derived Neurotrophic Factor ; Humans ; Infant* ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight* ; Interleukin-1beta ; Interleukin-6 ; Models, Animal ; Neuroglia ; Phosphopyruvate Hydratase ; Pilot Projects* ; Transplants ; Umbilical Cord* ; Umbilical Veins

As we face an increase of the adult population suffering from dementia, a typical senile disorder, it is imperative to develop appropriate tools for early detection and differential diagnosis of dementia. Recently, proteomics techniques have been proposed to be used for diagnosis of neurodegenerative disorders by identifying numerous biological markers that are known to increase or decrease in the cerebrospinal fluid or serum of dementic patients. Protein chip analysis, one of the most important techniques of proteomics, is suggested to be useful for examining various modifications of proteins as the high throughput screening method using small volumes of precious samples in a short period. We describe here a list of biological markers, such as A beta, APP, tau, ubiquitin, S100B, soluble IL-6 receptor, beta 2 micoglobulin and prostaglandin E2, proposing that these molecules can be used as biochemical markers of dementia. Therefore, we suggest that the proteomic approaches to analyze the amount and modifications of these proteins might be powerful tools for early detection and differential diagnosis of various neurodegenerative disorders as well as assessment of disease progress.
Adult ; Biomarkers ; Cerebrospinal Fluid ; Dementia ; Diagnosis* ; Diagnosis, Differential ; Dinoprostone ; Humans ; Mass Screening ; Neurodegenerative Diseases* ; Protein Array Analysis* ; Proteomics* ; Receptors, Interleukin-6 ; Ubiquitin

PURPOSE: This study was performed to evaluate the changes in the IL-1beta and the IL-6 concentrations in cerebrospinal fluid (CSF) after initial successful cardiopulmonary resuscitation (CPR), to examine the difference in the IL-1beta and the IL-6 concentrations in CSF between the cerebral performance category (CPC) 1-2 group and CPC 3-5 group after successful CPR, and to identify early makers predicting the outcome after successful CPR. METHODS: We studied prospectively 10 patients with spontaneous circulation after CPR. Samples of CSF were taken at 20 min, 4 hr, 24 hr, and 48 hr after restoration of spontaneous circulation. The control group was consisted of the nonspecific 6 patients in brain computed tomography and CSF finding among the visited patients in emergency department with complaints of headache. The CSF IL-1beta and IL-6 were measured by using enzyme-linked immunosorbent assays. RESULTS: 1) The concentrations of CSF IL-6 for CPC 3-5 were higher in the successful CPR group than in the control group. 2) In the severely neurologically disabled group (CPC 3-5), the concentrations of CSF IL-6 were significantly higher at 20 min 4 hr, 24 hr and 48 hr after successful CPR than they were in the mildly neurologically disabled group(CPC 1-2). 3) The concentrations of CSF IL-6 in the severely neurologically disabled group (CPC 3-5) reached peak levels at 24 hours after successful CPR. 4) The concentrations of CSF IL-1beta did not differ between the two groups. CONCLUSION: Our study indicates that CSF IL-6 is increased more in the severely neurologically disabled group (CPC 3-5) than it is in the mildly neurologically disabled group (CPC 1-2) after successful CPR. We found a significant relationship between the concentration of CSF IL-6 and initial outcome for the CPR patient. Thus, we suggest that CSF IL-6 might play a role in brain ischemic-reperfusion injury and might be used as a prognostic marker after successful CPR.
Brain ; Cardiopulmonary Resuscitation ; Cerebrospinal Fluid ; Emergency Service, Hospital ; Enzyme-Linked Immunosorbent Assay ; Headache ; Heart Arrest* ; Humans ; Hypoxia-Ischemia, Brain* ; Interleukin-1beta ; Interleukin-6 ; Prospective Studies

OBJECTIVE: The cytokine interleukin-6(IL-6) plays a major role in initiating the acute phase response, especially in the production of acute phase reactants. The objective of this study is to determine whether serum IL-6 and cerebrospinal fluid(CSF) IL-6 levels were elevated at time of admission after head injury, serum IL-6 and CSF IL-6 levels related temporally to clinical improvement, severity of head injury with Glasgow Coma Scale(GCS) score and increased intracranial pressure(IICP). METHODS: All 21 patients(19 males and 2 females) with brain injury, managed in our institute between Aug 1996 and Jun 1998 were included in this study. Serum samples from all the 21 patients and CSF samples from 12 patients with low GCS score were analyzed for IL-6. IL-6 determination with enzyme-linked ELISA kits obtained from Quantikine(r). RESULTS: The values of IL-6 in serum and CSF in 21 patients with GCS score between 4 and 14(mean=9) were observed for 3-5 days after head injury. Peak elevation of serum IL-6 was observed on first day(8.2+/-4.9pg/ml) and then decreased to 4.0+/-3.6pg/ml on fifth day. Serum IL-6 levels decreased significantly faster in patients with GCS score of 8 through 11, compared with those of GCS score below 8. The patients showed markedly elevated and variable CSF IL-6 levels on admission(46.6+/-4.2pg/ml;normal, below 20.6+/-5.8pg/ml). CONCLUSION: This study demonstrates that the IL-6 level is related to the severity of traumatic brain injury.
Acute-Phase Proteins ; Adult* ; Brain Injuries ; Cerebrospinal Fluid* ; Coma ; Craniocerebral Trauma* ; Enzyme-Linked Immunosorbent Assay ; Head* ; Humans ; Interleukin-6* ; Intracranial Pressure ; Male

OBJECTIVE: The cytokine interleukin-6(IL-6) plays a major role in initiating the acute phase response, especially in the production of acute phase reactants. The objective of this study is to determine whether serum IL-6 and cerebrospinal fluid(CSF) IL-6 levels were elevated at time of admission after head injury, serum IL-6 and CSF IL-6 levels related temporally to clinical improvement, severity of head injury with Glasgow Coma Scale(GCS) score and increased intracranial pressure(IICP). METHODS: All 21 patients(19 males and 2 females) with brain injury, managed in our institute between Aug 1996 and Jun 1998 were included in this study. Serum samples from all the 21 patients and CSF samples from 12 patients with low GCS score were analyzed for IL-6. IL-6 determination with enzyme-linked ELISA kits obtained from Quantikine(r). RESULTS: The values of IL-6 in serum and CSF in 21 patients with GCS score between 4 and 14(mean=9) were observed for 3-5 days after head injury. Peak elevation of serum IL-6 was observed on first day(8.2+/-4.9pg/ml) and then decreased to 4.0+/-3.6pg/ml on fifth day. Serum IL-6 levels decreased significantly faster in patients with GCS score of 8 through 11, compared with those of GCS score below 8. The patients showed markedly elevated and variable CSF IL-6 levels on admission(46.6+/-4.2pg/ml;normal, below 20.6+/-5.8pg/ml). CONCLUSION: This study demonstrates that the IL-6 level is related to the severity of traumatic brain injury.
Acute-Phase Proteins ; Adult* ; Brain Injuries ; Cerebrospinal Fluid* ; Coma ; Craniocerebral Trauma* ; Enzyme-Linked Immunosorbent Assay ; Head* ; Humans ; Interleukin-6* ; Intracranial Pressure ; Male

Subarachnoid hemorrhage (SAH) induces an inflammatory reaction and may lead to ischemic brain damage. The pathogenesis of brain dysfunction and delayed ischemic symptoms remain difficult to understand despite extensive surveys of such reactions. Cytokine production in the central nervous system following SAH and its relation with clinical outcome have hardly been studied. This study was aimed to determine whether the levels of IL-1 beta, IL-6 and TNF-alpha in the initial cerebrospinal fluid would increase following aneurysmal SAH, and be related with development of delayed ischemic deficit and clinical outcome. Nineteen patients suffering from aneurysmal SAH and 12 control volunteers were the subjects in this study. Cerebrospinal fluid samples were obtained on admission and the levels of each cytokine were determined with enzyme-linked immunosorbent assay. Patients with aneurysmal subarachnoid hemorrhage showed elevated levels of IL-1 beta, and TNF-alpha on admission. The patients with poor neurological status showed high levels of IL-1 beta, and IL-6. The patients who developed delayed ischemic deficit had high level of IL-6. We suggest that elevated level of IL-6 in cerebrospinal fluid of patients with aneurysmal SAH on admission can predict the high risk of delayed ischemic deficit.
Adult ; Aged ; Brain Ischemia/*cerebrospinal fluid/*diagnosis/immunology ; Cytokines/*cerebrospinal fluid ; Female ; Glasgow Outcome Scale ; Human ; Interleukin-1/cerebrospinal fluid ; Interleukin-6/cerebrospinal fluid ; Male ; Middle Age ; Predictive Value of Tests ; Subarachnoid Hemorrhage/*cerebrospinal fluid/*diagnosis/immunology ; Tumor Necrosis Factor/cerebrospinal fluid