Factors In Cerebrospinal Fluid Research Articles

Long-term elevation of complement factors in cerebrospinal fluid of patients with Borna disease virus 1 (BoDV-1) encephalitis.

Borna disease virus 1 (BoDV-1) causes rare but severe zoonotic infections in humans, presenting as severe encephalitis. The case-fatality risk is very high and no effective countermeasures have been established so far. An immunopathology is presumed, while data on immune responses in humans are limited. Evidence of a role of the complement system in various neurological disorders and central nervous viral infections is increasing and specific inhibitors are available as therapeutic options. In this study, we investigated factors of the complement system in the cerebrospinal fluid (CSF) of patients with BoDV-1 infections (n = 17) in comparison to non-inflammatory control CSF samples (n = 11), using a bead-based multiplex assay. In addition, immunohistochemistry was performed using post-mortem brain tissue samples. We found an intrathecal elevation of complement factors of all complement pathways and an active cascade during human BoDV-1 infections. The increase of certain complement factors such as C1q was persistent and C3 complement deposits were detected in post-mortem brain sections. Intrathecal complement levels were negatively correlated with survival. Further investigations are warranted to clarify, whether targeting the complement cascade by specific inhibitors might be beneficial for patients suffering from severe BoDV-1 encephalitis.

Role of nerve growth factor on cognitive impairment in patients with Alzheimer's disease carrying apolipoprotein E ε4.

To investigate the roles of neurotrophic factors on cognition in patients with Alzheimer's disease (AD) carrying Apolipoprotein E (APOE) ε4. Totals of 173 patients with AD were divided into APOE ε4 carrier and non-carrier groups, and their demographics, cognition, and neurotrophic factors in cerebrospinal fluid (CSF) were compared. Multiple linear regression analyses were performed to assess correlations among APOE ε4, neurotrophic factors and cognition. Mediation analyses were conducted to assess the sequential associations among APOE ε4, nerve growth factor (NGF), and cognition. Global cognition and multiple domains were impaired in the APOE ε4 carrier group (all p < 0.05). NGF level in the APOE ε4 carrier group was lower than that in the non-carrier group (p = 0.016). NGF level showed significant correlations with both global and multiple domains cognitions. Specifically, NGF mediated the association between APOE ε4 and Animal Fluency Test score (β, -0.45; 95% CI [-0.96, -0.07]; p < 0.001) and Trail Making Test-A (time) (β, 0.15; 95% CI [0.01, 0.33]; p < 0.001). APOE ε4 is associated with cognitive impairment, and those carrying APOE ε4 have decreased NGF level in CSF. Declined NGF level is correlated with compromised cognition. NGF mediates APOE ε4-associated cognitive impairment.

The roles of apolipoprotein E ε4 on neuropathology and neuroinflammation in patients with Alzheimer's disease.

To explore the roles of apolipoprotein E (APOE) ε4 on the neuropathology and neuroinflammation in Alzheimer's disease (AD) patients. AD patients were divided into the APOE ε4 carrier and the APOE ε4 non-carrier groups according to APOE genotype. Demographic information, cognitive function, the levels of neuropathological proteins and neuroinflammatory factors in cerebrospinal fluid (CSF) were compared between the two groups, and their correlations were subsequently analyzed. β amyloid protein (Aβ)1-42 level from the APOE ε4 carrier group was significantly lower than that from the non-carrier group (p = 0.023), which was associated with worse cognitive function. The nitric oxide (NO) level was significantly elevated in the APOE ε4 carrier group compared to the non-carrier group (p = 0.016), which was significantly and positively correlated with the Trail Making Test (TMT)-A-time (r = 0.21, p = 0.026) and TMT-B-time (r = 0.38, p < 0.01). APOE ε4 is associated with poorer cognition, particularly the early symptoms of memory, language, and attention. APOE ε4 is associated with lower Aβ1-42 level, and the more numbers of APOE ε4 are carried, the lower level of Aβ1-42 is measured. APOE ε4 is associated with elevated NO level, which is linked to the impaired attention and executive function.

Relationship between miRNA-21, miRNA-155, and miRNA-182 expression and inflammatory factors in cerebrospinal fluid from patients with multiple sclerosis

BackgroundThe impact of microRNAs (miRNAs) on the differentiation and function of inflammatory cells is well-established. MiRNAs play a crucial role in modulating the expression of pro-inflammatory genes in neuronal cells as well. With this knowledge in mind, our study aimed to explore the relationship between the expression of miRNAs and inflammatory markers in the cerebrospinal fluid (CSF) of patients diagnosed with multiple sclerosis (MS). By investigating this relationship, we aimed to gain insights into the potential involvement of miRNAs in the regulation of inflammation in the context of MS. Materials and methodsThe expression levels of miRNA-21, miRNA-155, and miRNA-182 in cerebrospinal fluid (CSF) samples from multiple sclerosis (MS) patients and controls were determined by RT-PCR. CSF levels of the inflammatory cytokines IL-1β, IL-6, and TNF-α were measured by enzyme-linked immunosorbent assay (ELISA). In addition, high-sensitivity C-reactive protein (hs-CRP) levels were measured by quantitative turbidimetry. ResultsThe expression levels of microRNAs and inflammatory factors were found to be significantly higher in the CSF of MS patients compared to controls (P < 0.05). Receiver operating characteristics (ROC) analysis revealed that miRNA-21, miRNA-182, and miRNA-155 had a high area under the curve (AUC) in discriminating MS patients, with AUC values of 0.97 (P < 0.0001) for miRNA-21, 0.97 (P < 0.0001) for miRNA-182, and 0.96 (P < 0.0001) for miRNA-155. Notably, CSF miRNA-155 showed the highest accuracy in correctly diagnosing MS. Furthermore, a statistically significant relationship was observed between inflammatory cytokines and miRNA-21, miRNA-155 and miRNA-182. ConclusionOur results demonstrated that cerebrospinal fluid (CSF) levels of IL-1β, IL-6, TNF-α, hs-CRP and specific miRNAs serve as biomarkers for assessing central nervous system (CNS) inflammation and neurodegenerative processes in patients with multiple sclerosis (MS).

The comparative analysis of selected interleukins and proinflammatory factors in CSF among de novo diagnosed patients with RRMS

ObjectivesCytokines play a key role in neuroinflammation, which is present in every subset of multiple sclerosis (MS). The aim of the study was to assess levels of selected interleukins and proinflammatory factors in cerebrospinal fluid (CSF) among patients diagnosed with relapsing-remitting multiple sclerosis (RRMS). MethodsOne hundred eighteen patients diagnosed de novo with RRMS were enrolled in the study. We analysed the relationships between selected cytokines’ levels depending on the age at diagnosis, time from the first symptoms to diagnosis and presence of MRI lesions. ResultsAmong the study group the levels of IL-5 and IL-13 increased with the age at the diagnosis of MS. The concentration of IL-10 was lower in group of patients over the age of 35. The levels of IFN-γ, TNF-α, IL-5, IL-10 and IL-15 increased with the longer time from the first symptoms to diagnosis. Positive correlations were found between the levels of IL-2and IL-12, IL-17, IL-4, IL-1RA as well as IL-1 and IL-4, IL-17. The concentration of IL-5 correlated positively with IL-4, IL-9 and IL-13. The level of IL-10 increased with IL-6 and IL-9 concentrations. A negative correlation was found for IL-10 and IL-4. In turn, between IL-13 and both IL-5 and IL-9, the relationship was positive. The level of IL-2 was significantly higher among patients without gadolinium-enhanced (Gd(+)) MRI lesions. ConclusionsThe results of the study provide new insight into the role of selected molecules in the development of inflammation in MS. It might be crucial in planning the most adequate immunomodulatory therapy.

Cytokine response in cerebrospinal fluid of meningitis patients and outcome associated with pneumococcal serotype

Streptococcus pneumoniae causes life-threatening meningitis. Its capsular polysaccharide determines the serotype and influences disease severity but the mechanism is largely unknown. Due to evidence of elevated cytokines levels in the meningeal inflammatory response, we measured 41 cytokines/chemokines and growth factors in cerebrospinal fluid (CSF) samples from 57 South African meningitis patients (collected in the period 2018–2019), with confirmed S. pneumoniae serotypes, using a multiplexed bead-based immunoassay. Based on multivariable Bayesian regression, using serotype 10A as a reference and after adjusting for HIV and age, we found IL-6 concentrations significantly lower in patients infected with serotypes 6D (undetectable) and 23A (1601 pg/ml), IL-8 concentrations significantly higher in those infected with 22A (40,459 pg/ml), 7F (32,400 pg/ml) and 15B/C (6845 pg/ml), and TNFα concentration significantly higher in those infected with serotype 18A (33,097 pg/ml). Although a relatively small number of clinical samples were available for this study and 28% of samples could not be assigned to a definitive serotype, our data suggests 15B/C worthy of monitoring during surveillance as it is associated with in-hospital case fatality and not included in the 13-valent polysaccharide conjugate vaccine, PCV13. Our data provides average CSF concentrations of a range of cytokines and growth factors for 18 different serotypes (14, 19F, 3, 6A, 7F, 19A, 8, 9N, 10A, 12F, 15B/C, 22F, 16F, 23A, 31, 18A, 6D, 22A) to serve as a basis for future studies investigating host–pathogen interaction during pneumococcal meningitis. We note that differences in induction of IL-8 between serotypes may be particularly worthy of future study.

Preparation of Let-7b Nanocomposite and Its Effect on the Level of Inflammatory Factors in Cerebrospinal Fluid of Purulent Meningitis

This study was to explore the effect and mechanism of Let-7b nanocomposite on the expression of inflammatory factors in the cerebrospinal fluid (CSF) of purulent meningitis. 45 patients with purulent meningitis (PM) were selected as observation group (group A), and 38 patients with normal CSF without central nervous system diseases were selected as the control group (group B). The CSF of the two groups were collected to detect the inflammatory factors interleukin-8 (IL-8), macrophage inflammatory protein-1α (MIP-1α), matrix metalloproteinase 9 (MMP9), interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α), and Let-7b level with the double antibody sandwich enzyme-linked immunosorbent assay (ELISA). The Let-7b nanocomposite was prepared, and its morphology, particle size, and Zeta potential were analyzed. In addition, the degradation kinetics, cytotoxicity, and phagocytic efficiency (PE) of Let-7b nanocapsules were detected. 36 healthy adult New Zealand (NZL) rabbits were randomly grouped into a control group (group C) (0.9% normal saline (NS)), a model group (Escherichia coli (E. coli) modeling, group D), and a test group (E. coli modeling + Let-7b nanocapsules, group E), with 12 rabbits in each group. The changes of inflammatory factors in CSF of the three groups were detected and compared. It was found that the expression levels of IL-8 and IL-1 β in the group A were much higher than those in the group B (P &lt; 0.01), and the MMP9 and TNF-α levels in the group B were much lower in contrast to the group A (P &lt; 0.001). The expression of Let-7b in the group A was lower obviously in contrast to the group B (P &lt; 0.001). Let-7b nanocapsules were irregularly spherical, with an average particle size (APS) of 23.1 nm, a polydispersity index (PDI) of 0.232, and the Zeta potential of around +15 mV. Let-7b nanocapsules showed obvious polymer shell absorption peaks at 1,015 cm-1, 1,228 cm-1, and 1,547 cm-1. The IL-8 and IL-1β levels of the group D were greatly different from those in the other two groups (P &lt; 0.01). The levels of TNF-α and MMP9 in the group D were greatly different in contrast to the group C (P &lt; 0.001) and the group E (P &lt; 0.01). It indicated that Let-7b nanocomposite could lower the expression levels of IL-8, IL-1β, MMP9, and TNF-α in the CSF of patients with purulent meningitis dramatically, which provides a reliable basis for immunotherapy of purulent meningitis with Let-7b.

ADMSC Exo-MicroRNA-22 improve neurological function and neuroinflammation in mice with Alzheimer's disease.

The previous study by our group has found that miRNA‐22 can inhibit pyroptosis by targeting GSDMD and improve the memory and motor ability of mice with Alzheimer's disease (AD) mice by inhibiting inflammatory response. In recent years, stem cells and their exosomes have been reported to have good therapeutic effects on AD; therefore, we hypothesize that miRNA‐22 is likely to play a synergistic therapeutic effect. In this study, adipose‐derived mesenchymal stem cells (ADMSCs) were transfected into miRNA‐22 mimic to obtain miRNA‐22 loaded exosomes (Exo‐miRNA‐22), which was further used for the treatment and nerve repair of AD. In brief, 4‐month‐old APP/PS1 mice were assigned into the control group, Exo and Exo‐miRNA‐22 groups. After exosome transplantation, we observed changes in the motor and memory ability of mice. In addition, ELISA was used to detect the expression of inflammatory factors in cerebrospinal fluid and peripheral blood, Nissl staining was used to assess the survival of mouse nerve cells, immunofluorescence staining was used to determine the activation of microglia, and Western blot was utilized to detect the expression of pyroptosis‐related proteins. As a result, the nerve function and motor ability were significantly higher in mice in the Exo‐miRNA‐22 group than those in the control group and Exo group. Meanwhile, the survival level of nerve cells in mice was higher in the Exo‐miRNA‐22 group, and the expression of inflammatory factors was lower than that of the Exo group, indicating Exo‐miRNA‐22 could significantly suppress neuroinflammation. In vitro culture of PC12 cells, Aβ25‐35‐induced cell damage, detection of PC12 apoptotic level, the release of inflammatory factors and the expression of pyroptosis‐related proteins showed that Exo‐miRNA‐22 could inhibit PC12 apoptosis and significantly decrease the release of inflammatory factors. In this study, we found that miRNA‐22‐loaded ADMSC‐derived exosomes could decrease the release of inflammatory factors by inhibiting pyroptosis, thereby playing a synergetic therapeutic role with exosomes on AD, which is of great significance in AD research.

Parkinson's Disease With Depression: The Correlations Between Neuroinflammatory Factors and Neurotransmitters in Cerebrospinal Fluid.

Background: To explore the changes of neuroinflammatory factors in cerebrospinal fluid (CSF) and their correlation with monoamine neurotransmitters in Parkinson’s disease (PD) with depression (PD-D) patients.Methods: Neuroinflammatory factors and neurotransmitters in CSF were measured and compared between PD with no depression (PD-ND) and PD-D groups. The relationship between PD-D and neuroinflammatory factors was studied by binary logistic regression equation, and the related factors of PD-D were adjusted. The correlations of the levels of neuroinflammatory factors and neurotransmitters in PD-D group were analyzed.Results: The levels of tumor necrosis factor (TNF)-α in CSF from PD-D group were significantly higher and there were no significant differences in the levels of interleukin-1β, prostaglandin (PG) E2, hydrogen peroxide (H2O2), and nitric oxide (NO). The 24-item Hamilton Depression Scale (HAMD-24) score was positively correlated with the level of TNF-α in CSF. Binary logistic regression showed that the OR of CSF TNF-α level was 1.035 (95% CI 1.002–1.069). The level of dopamine (DA) in CSF of PD-D group was significantly lower than that in PD-ND group. TNF-α level was negatively correlated with DA level in CSF from PD patients (r = −0.320, P = 0.003).Conclusions: Neuroinflammatory factors, especially TNF-α, may play an important role in PD-D. It may cause damage to DA neurons and lead to the depletion of DA, which is related to the occurrence and development of PD-D.

Tracking Calcium Dynamics and Immune Surveillance at the Choroid Plexus Blood-Cerebrospinal Fluid Interface

The choroid plexus (ChP) epithelium is a source of secreted signaling factors in cerebrospinal fluid (CSF) and a key barrier between blood and brain. Here, we develop imaging tools to interrogate these functions in adult lateral ventricle ChP in whole-mount explants and in awake mice. By imaging epithelial cells in intact ChP explants, we observed calcium activity and secretory events that increased in frequency following delivery of serotonergic agonists. Using chronic two-photon imaging in awake mice, we observed spontaneous subcellular calcium events as well as strong agonist-evoked calcium activation and cytoplasmic secretion into CSF. Three-dimensional imaging of motility and mobility of multiple types of ChP immune cells at baseline and following immune challenge or focal injury revealed a range of surveillance and defensive behaviors. Together, these tools should help illuminate the diverse functions of this understudied body-brain interface.

Astrocytic IGFBP2 and CHI3L1 in cerebrospinal fluid drive cortical metastasis of HER2+breast cancer.

The brain is often reported as the first site of recurrence among breast cancer patients overexpressing human epidermal growth factor receptor 2 (HER2). Although most HER2+tumors metastasize to the subcortical region of the brain, a subset develops in the cortical region. We hypothesize that factors in cerebrospinal fluid (CSF) play a critical role in the adaptation, proliferation, and establishment of cortical metastases. We established novel cell lines using patient biopsies to model breast cancer cortical and subcortical metastases. We assessed the localization and growth of these cells in vivo and proliferation and apoptosis in vitro under various conditions. Proteomic analysis of human CSF identified astrocyte-derived factors that support the proliferation of cortical metastases, and we used neutralizing antibodies to test the effects of inhibiting these factors both in vivo and in vitro. The cortical breast cancer brain metastatic cells exhibited greater proliferation than subcortical breast cancer brain metastatic cells in CSF containing several growth factors that nourish both the CNS and tumor cells. Specifically, the astrocytic paracrine factors IGFBP2 and CHI3LI promoted the proliferation of cortical metastatic cells and the formation of metastatic lesions. Disruption of these factors suppressed astrocyte-tumor cell interactions in vitro and the growth of cortical tumors in vivo. Our findings suggest that inhibition of IGFBP2 and CHI3LI signaling, in addition to existing treatment modalities, may be an effective therapeutic strategy targeting breast cancer cortical metastasis.

Investigation on the mechanism of mafenide in inhibiting pyroptosis and the release of inflammatory factors

ObjectiveThe present study was designed to investigate the roles and mechanism of mafenide (MAF) in targeted inhibition of Gasdermin D (GSDMD) cleavage and in suppressing pyroptosis. MethodsLipopolysaccharide (LPS) and Nigericin were used to induce pyroptosis in mouse bone marrow-derived macrophages (iBMDM) and mouse microglia (BV2). Lactate dehydrogenase (LDH) release rate and Propidium Iodide (PI) uptake rate were used to detect cytotoxicity, Western blot was used to detect the protein expression, and Enzyme-linked immunosorbent assay (ELISA) was utilized to detect the expression of inflammatory factors from culture medium. MAF was labeled with biotin and subsequently subjected to Pull-down assay to detect its binding to GSDMD. GSDMD-Asp275 site was further mutated to validate the binding of MAF to GSDMD. Finally, the effects of MAF on inflammatory factor release and microglial activation were confirmed in the APP/PS12 animal model. ResultsMAF could inhibit pyroptosis in iBMDM and microglia BV2, and decrease the release of inflammatory factors. MAF could inhibit GSDMD cleavage by directly binding to the GSDMD-Asp275 site, while the expression of p30-GSDMD was simultaneously down-regulated and the release of inflammatory factors was decreased. MAF could reduce the levels of inflammatory factors in cerebrospinal fluid and peripheral blood of APP/PS1 mice, and suppress the activation of microglia. ConclusionThe mechanism underlying the regulation of MAF on inflammatory response was correlated with the inhibition of pyroptosis. MAF could inhibit GSDMD cleavage by directly binding to GSDMD.

Tracking Calcium Dynamics and Immune Surveillance at the Choroid Plexus Blood-Cerebrospinal Fluid Interface

The choroid plexus (ChP) epithelium is a source of secreted signaling factors in cerebrospinal fluid (CSF) and a key barrier between blood and brain. Here, we develop imaging tools to interrogate these functions in adult lateral ventricle ChP in wholemount explants and in awake mice. By imaging epithelial cells in intact ChP explants, we observed calcium activity and secretory events that increased in frequency following delivery of serotonergic agonists. Using chronic two-photon imaging in awake mice, we observed spontaneous subcellular calcium events as well as strong agonist-evoked calcium activation and cytoplasmic secretion into CSF. Three-dimensional imaging of motility and mobility of multiple types of ChP immune cells at baseline and following immune challenge or focal injury revealed a range of surveillance and defensive behaviors. Together, these tools should help illuminate the diverse functions of this understudied body-brain interface.

Tremor-Dominant in Parkinson Disease: The Relevance to Iron Metabolism and Inflammation.

Background: Tremor is one of the most predominant symptoms of patients with Parkinson disease (PD), but the underlying mechanisms for tremor relating to iron and its metabolism-related proteins and the inflammatory factors in cerebrospinal fluid (CSF) and serum have not been fully elucidated.Methods: A total of 135 PD patients were divided into a tremor-dominant (PD-TD) group (N = 74) and a postural instability and gait difficulty-dominant (PD-PIGD) group (N = 39) based on the ratio of mean tremor score to the mean bradykinesia/rigid score of the Unified Parkinson’s Disease Rating Scale (UPDRS) III. Age and sex-matched healthy controls were recruited (N = 35). Demographic variables were evaluated; iron and its metabolism-related proteins and the inflammatory mediators in both CSF and serum were measured in these groups. The relevance of iron metabolism, inflammation and PD-TD were analyzed.Results: (1) The PD-TD group had significantly decreased L-ferritin, increased iron levels in CSF and increased ferritin levels in the serum compared with the PD-PIGD and control groups (P < 0.05). (2) The PD-TD group had significantly enhanced IL-6 levels in both CSF and serum compared with the PD-PIGD and control groups (P < 0.05). (3) In CSF, the IL-6 level was increased as the iron level was elevated in the PD-TD group (r = 0.308, P = 0.022). In serum, the IL-6 level was increased as the ferritin level was elevated in the PD-TD group (r = 0.410, P = 0.004).Conclusion: The interplay between disturbed iron metabolism and relevant inflammation might modulate clinical phenotypes of PD.

Relevant analyses of pathogenic bacteria and inflammatory factors in neonatal purulent meningitis.

Pathogenic bacteria and inflammatory factors in neonatal purulent meningitis (PM) were investigated to explore the diagnostic value of inflammatory factors in PM, to clarify the etiology, and to provide evidence for rational clinical treatment. Seventy-four neonates who were diagnosed with PM and were bacteriogically positive in Daqing Longnan Hospital from January 2012 to December 2015 were retrospectively analyzed and used as observation group. Another 74 neonates simultaneously hospitalized with non-PM factors were selected as control group. The levels of C-reactive protein (CRP) and β 2 microglobulin (β2MG) in cerebrospinal fluid in pediatric patients were measured, and the separation culture and identification of pathogenic bacteria were carried out at the same time. The results showed that i) neonatal PM often lacked specific clinical manifestations; ii) high risk factors of neonatal PM included gestational age, body weight <2,500 g, neonatal asphyxia, premature rupture of membranes, and umbilical or pulmonary infection; iii) the levels of CRP and β2MG in the cerebrospinal fluid in the neonatal PM group were significantly higher than those in the control group (P<0.05), and the neonatal PM group had obviously decreased levels of CRP and β2MG in the cerebrospinal fluid after treatment compared with those before treatment (P<0.05); iv) the positive rate of Gram-negative bacilli (G-bacilli) showed an increasing trend year by year in the past 4 years. Seventy-four strains of bacteria were isolated from the cerebrospinal fluid in neonatal PM group, including 45 strains of Gram-positive cocci (G+cocci, accounting for 60.81%) and 29 strains of G-bacilli (accounting for 39.19%). Among them, the top three were Escherichia coli, coagulase-negative staphylococci (CNS) and Streptococcus. These findings indicated that for suspected PM pediatric patients with high risk factors, the inflammatory factors in cerebrospinal fluid and the etiology should be investigated via lumbar puncture as early as possible to confirm the diagnosis. Pathogenic bacteria of meningitis mainly are Escherichia coli, CNS and Streptococcus, and the characteristics of pathogenic bacteria should be considered during experiential medication. The incidence rate of PM due to Streptococcus has an upward tendency and great damage, needing to arouse high attention in clinic.

A study on correlations of procalcitonin and interleukin-6 with viral meningitis.

To study the change rules of inflammatory factors in cerebrospinal fluid (CSF) and serum of patients with viral meningitis. 742 patients with suspected viral meningitis admitted to Department of Neurosurgery in our hospital from August 2012 to May 2016 were selected as research objects and retrospectively analyzed. 536 patients were diagnosed with viral meningitis by CSF with the lumbar puncture and brain computed tomography (CT), while the other 206 patients were diagnosed with non-infectious nervous system disease, as the control group. The levels of inflammatory factors interleukin-6 (IL-6) in peripheral blood and procalcitonin (PCT) in cerebrospinal fluid were detected and compared between two groups of patients. Compared with those in control group, the white blood cell (WBC) count, and levels of serum IL-6 and PCT in cerebrospinal fluid of patients with viral meningitis were all increased (p<0.01). PCT and IL-6 were positively correlated with viral meningitis (r=0.8267, 0.9234). The sensitivity of the two items was 77.81% and 81.32%, respectively, and the specificity was 90.53% and 88.64%, respectively. The levels of inflammatory factors IL-6 and PCT in serum and CSF of patients with viral meningitis are slightly increased. The detection of the expression levels of IL-6 and PCT in patients with viral meningitis is of great significance for the preliminary diagnosis and rehabilitation of viral meningitis.

Iron deposition in substantia nigra: abnormal iron metabolism, neuroinflammatory mechanism and clinical relevance

Parkinson disease (PD) is associated with multiple factors, including iron, which is demonstrated to deposit excessively in PD brains. We detected iron deposition by susceptibility weighted image (SWI) and measured the levels of iron metabolism-related proteins and inflammatory factors in cerebrospinal fluid (CSF) and serum of PD patients and control subjects. Clinical symptoms of PD were evaluated by series of rating scales. Relationships among above factors were analyzed. Results showed that corrected phase (CP) value of substantia nigra (SN) was significantly decreased in PD group compared to control group, hence, SN was the main region with excessive iron deposition. In PD group, ferritin was significantly elevated in CSF and reduced in serum compared to control group, and levels of ferritin in CSF and serum were both significantly and positively correlated with CP value of SN, thus, abnormal iron metabolism in central and peripheral systems was associated with iron deposition. CP value of SN in PD group was significantly and negatively correlated with interleukin-1β level in CSF, so interleukin-1β might be a neuroinflammatory factor produced by excessive iron in SN. Iron deposition in SN was significantly correlated with motor symptoms and part of non-motor symptoms of PD.

Inhibition of neuropathic hyperalgesia by intrathecal bone marrow stromal cells is associated with alteration of multiple soluble factors in cerebrospinal fluid.

Injury-induced neuropathic pain remains a serious clinical problem. Recent studies indicate that bone marrow stromal cells (BMSCs) effectively attenuate chronic neuropathic pain in animal models. Here, we examined the therapeutic effect of intrathecal administration of BMSCs isolated from young (1-month-old) rats on pain hypersensitivity induced by tibial nerve injury. Cerebrospinal fluid (CSF) was collected and analyzed to examine the effect of BMSC administration on the expression of 67 soluble factors in CSF. A sustained remission in injury-induced mechanical hyperalgesia was observed in BMSC-treated rats but not in control animals. Engrafted BMSCs were observed in spinal cords and dorsal root ganglia at 5weeks after cell injection. Injury significantly decreased the levels of six soluble factors in CSF: intercellular adhesion molecule 1 (ICAM-1), interleukin-1β (IL-1β), IL-10, hepatocyte growth factor (HGF), Nope protein, and neurogenic locus notch homolog protein 1 (Notch-1). Intrathecal BMSCs significantly attenuated the injury-induced reduction of ICAM-1, IL-1β, HGF, IL-10, and Nope. This study adds to evidence supporting the use of intrathecal BMSCs in pain control and shows that this effect is accompanied by the reversal of injury-induced reduction of multiple CSF soluble factors. Our findings suggest that these soluble factors may be potential targets for treating chronic pain.

Atorvastatin for treating spontaneous subarachnoid hemorrhage: study protocol for a randomized double-blind placebo-controlled trial

Background: Animal studies have confirmed that statins have neuroprotective effects during and following a subarachnoid hemorrhage; however, the therapeutic effect of statins in humans remains controversial. The interpretation of data currently available on the clinical application of statins to spontaneous subarachnoid hemorrhage is limited by the small sample sizes used in the studies, making it difficult to draw valid conclusions regarding the multiple neuroprotective effects of statins. Thus, we propose to perform a randomized double-blind placebo-controlled parallel-group clinical trial to determine the effects of atorvastatin on spontaneous subarachnoid hemorrhage, apoptosis-related factors, and serum inflammatory factors in cerebrospinal fluid and to observe its neuroprotective effect mediated by relieving vasospasm. Methods/Design: This is a randomized parallel-group placebo-controlled double-blind clinical trial. This trial will recruit 300 patients with spontaneous subarachnoid hemorrhage from the Department of Neurosurgery, 101 st Hospital of PLA (Wuxi Taihu Hospital). These patients will be equally and randomly assigned to atorvastatin (40 mg/day) and placebo control groups. Outcomes will be evaluated at baseline, 3, 5, and 14 days after hemorrhage, and 6 months after discharge. The primary outcomes will be the results of computed tomography (CT) angiography combined with CT perfusion imaging and conventional CT. The secondary outcomes will be cerebrospinal fluid analysis, blood testing (tumor necrosis factor α, vascular endothelial growth factor, interleukin-6, and C-reactive protein levels), and the Hunt-Hess classification, the results of transcranial Doppler ultrasonography, and the scores on the Glasgow Coma Scale, the Glasgow Outcome Scale, and the National Institutes of Health Stroke Scale. Discussion: The results of this trial will provide data on the clinical application and neuroregenerative effect of atorvastatin in the acute stage of spontaneous subarachnoid hemorrhage. Trial registration: This trial was registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-14005395) on 18 May 2014.

Predictors of clinical outcomes in patients with neuropsychiatric systemic lupus erythematosus

IntroductionNeuropsychiatric systemic lupus erythematosus (NPSLE), a serious organ disorder with a variety of symptoms, has diverse therapeutic outcomes because of the variability of NPSLE manifestations. A comprehensive association study of NPSLE among clinical and immunopathogenic aspects and outcomes has not been conducted. MethodsWe analyzed the laboratory data, NPSLE symptoms, and clinical outcomes at 1yr post-treatment and the profiles of 27 cytokines, chemokines and growth factors in cerebrospinal fluid (CSF) samples using the Bio-Plex Human 27-plex panel from 28 NPSLE patients. Univariate and multivariable competing risks regression analyses were used to determine the predictive factors of clinical response. We also tried to predict the outcome of NPSLE by the 27 cytokines/chemokines/growth factors using a weighted-voting (WV) algorithm. ResultsOf the two males and 26 females (92.9%), 16 were non-responders at 1yr post-treatment; in the final model, the independent predictors of non-responders were longer disease durations of SLE (odds ratio [OR]: 1.490, 95% confidence interval [CI]: 1.143–2.461, p=0.0003) and patients with more than one NPSLE symptom types (OR: 15.14, 95% CI: 1.227–452.1, p=0.0334). The pretreatment CSF interleukin (IL)-6, IL-10, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) levels were significantly higher in the non-responders (p=0.0207, p=0.0054, p=0.0242 and p=0.0077, respectively). We identified six “minimum predictive markers:” IL-10, TNF-α, IL-6, IFN-γ, IL-4 and IL-13 by a WV algorithm that showed the highest accuracy (70.83%) and highest Matthews correlation coefficient (54.23%). ConclusionsWe have devised a numerical prediction scoring system that was able to separate the non-responders from responders. The patients with longer disease durations of SLE and those with more than one NPSLE symptom types had poorer outcomes. Our findings may indicate both the importance of making a diagnosis at an earlier phase for better therapeutic response and the usefulness of measuring multiple cytokines to predict NPSLE therapeutic outcomes.