Sample records for cerebrospinal fluid stasis

  1. Cerebrospinal fluid stasis and its clinical significance.

    PubMed

    Whedon, James M; Glassey, Donald

    2009-01-01

    We hypothesize that stasis of the cerebrospinal fluid (CSF) occurs commonly and is detrimental to health. Physiologic factors affecting the normal circulation of CSF include cardiovascular, respiratory, and vasomotor influences. The CSF maintains the electrolytic environment of the central nervous system (CNS), influences systemic acid-base balance, serves as a medium for the supply of nutrients to neuronal and glial cells, functions as a lymphatic system for the CNS by removing the waste products of cellular metabolism, and transports hormones, neurotransmitters, releasing factors, and other neuropeptides throughout the CNS. Physiologic impedance or cessation of CSF flow may occur commonly in the absence of degenerative changes or pathology and may compromise the normal physiologic functions of the CSF. CSF appears to be particularly prone to stasis within the spinal canal. CSF stasis may be associated with adverse mechanical cord tension, vertebral subluxation syndrome, reduced cranial rhythmic impulse, and restricted respiratory function. Increased sympathetic tone, facilitated spinal segments, dural tension, and decreased CSF flow have been described as closely related aspects of an overall pattern of structural and energetic dysfunction in the axial skeleton and CNS. Therapies directed at affecting CSF flow include osteopathic care (especially cranial manipulation), craniosacral therapy, chiropractic adjustment of the spine and cranium, Network Care (formerly Network Chiropractic), massage therapy (including lymphatic drainage techniques), yoga, therapeutic breath-work, and cerebrospinal fluid technique. Further investigation into the nature and causation of CSF stasis, its potential effects upon human health, and effective therapies for its correction is warranted. PMID:19472865

  2. CEREBROSPINAL FLUID STASIS AND ITS CLINICAL SIGNIFICANCE

    PubMed Central

    Whedon, James M.; Glassey, Donald

    2010-01-01

    We hypothesize that stasis of the cerebrospinal fluid (CSF) occurs commonly and is detrimental to health. Physiologic factors affecting the normal circulation of CSF include cardiovascular, respiratory, and vasomotor influences. The CSF maintains the electrolytic environment of the central nervous system (CNS), influences systemic acid-base balance, serves as a medium for the supply of nutrients to neuronal and glial cells, functions as a lymphatic system for the CNS by removing the waste products of cellular metabolism, and transports hormones, neurotransmitters, releasing factors, and other neuropeptides throughout the CNS. Physiologic impedance or cessation of CSF flow may occur commonly in the absence of degenerative changes or pathology and may compromise the normal physiologic functions of the CSF. CSF appears to be particularly prone to stasis within the spinal canal. CSF stasis may be associated with adverse mechanical cord tension, vertebral subluxation syndrome, reduced cranial rhythmic impulse, and restricted respiratory function. Increased sympathetic tone, facilitated spinal segments, dural tension, and decreased CSF flow have been described as closely related aspects of an overall pattern of structural and energetic dysfunction in the axial skeleton and CNS. Therapies directed at affecting CSF flow include osteopathic care (especially cranial manipulation), craniosacral therapy, chiropractic adjustment of the spine and cranium, Network Care (formerly Network Chiropractic), massage therapy (including lymphatic drainage techniques), yoga, therapeutic breathwork, and cerebrospinal fluid technique. Further investigation into the nature and causation of CSF stasis, its potential effects upon human health, and effective therapies for its correction is warranted. PMID:19472865

  3. Cerebrospinal Fluid Shunts

    Microsoft Academic Search

    Edward Rustamzadeh; Cornelius H. Lam

    Hydrocephalus is a congenital or acquired condition in which cerebrospinal fluid (CSF) accumulates in the ventricles and the\\u000a subarachnoid space around the brain (Fig. 1). It can lead to an increase in intracranial pressure. It has existed since primitive\\u000a man roamed the earth. Man’s understanding of anatomy and physiology has often consisted mainly of myth and superstition. The\\u000a earliest recording

  4. Bilateral spontaneous cerebrospinal fluid otorrhea

    Microsoft Academic Search

    Nobumitsu Honda; Yoshihisa Okouchi; Hidemitsu Sato; Tetsuji Sanuki; Naohito Hato; Naoaki Yanagihara; Shingo Murakami; Kiyofumi Gyo

    2004-01-01

    We present a rare case of bilateral cerebrospinal fluid (CSF) otorrhea via multiple bony defects in the left tegmen and a single defect with the herniated brain tissue on the right side. Initially, the patient complained of left hearing loss and fullness and was diagnosed with serous otitis media. After myringotomy, the pulsating watery discharge suggested CSF otorrhea. Five months

  5. Endoscopic repair of cerebrospinal fluid rhinorrhea

    Microsoft Academic Search

    VIVIAN H. MAO; WILLIAM M. KEANE; JOSEPH P. ATKINS; JOSEPH R. SPIEGEL; THOMAS O. WILLCOX; MARC R. ROSEN; DAVID REWS; DAVID ZWILLENBERG

    2000-01-01

    Endoscopic repair of cerebrospinal fluid rhinorrhea is a promising alternative to traditional repair techniques. This article reports our experience with 21 cases (10 spontaneous, 8 iatrogenic, and 3 traumatic). Various diagnostic radiographic modalities were used, including computer-aided techniques. Most repairs were accomplished with a free fascial graft positioned in the epidural space. Postoperative lumbar drainage was used in 15 cases.

  6. Tegmental Defects and Cerebrospinal Fluid Otorrhea

    Microsoft Academic Search

    Hannu J. Valtonen; Carl A. Geyer; Edward C. Tarlov; Carl B. Heilman; Dennis S. Poe

    2001-01-01

    Congenital tegmental defects that present as unsuspected cerebrospinal fluid (CSF) otorrhea are diagnostic and therapeutic challenges. We reviewed 5 such patients to determine an optimal strategy for evaluation. Five patients presented with watery otorrhea, 4 of them after ventilation tube placement, and only 1 with rhinorrhea. The preoperative analysis of middle ear effusion for ?2-transferrin was positive in 2\\/4, equivocal

  7. Paradoxical Postural Headaches in Cerebrospinal Fluid Leaks

    Microsoft Academic Search

    B Mokri; A J Aksamit; J LD Atkinson

    2004-01-01

    Two patients with cerebrospinal fluid (CSF) leak, one at the level of fourth thoracic spine and another with undetermined level of leak, presented with paradoxical postural headaches in that the headaches were present when in a horizontal position and resolved if the patients were upright. One patient improved spontaneously and the other responded to a targeted epidural blood patch. Paradoxical

  8. Cerebrospinal fluid cytokines in AIDS dementia complex

    Microsoft Academic Search

    Oreste Perrella; Pietro B. Carrieri; Domenico Guarnaccia; Mario Soscia

    1992-01-01

    We evaluated cerebrospinal fluid (CSF) and serum concentrations of interleukin-1-alpha (IL-1 alpha), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) in 30 patients with AIDS dementia complex (ADC), and in 20 HIV-seronegative subjects with other neurological diseases (OND). CSF TNF alpha, IL-1-alpha and IL-6 were more frequently detectable in ADC patients than in OND subjects. These cytokines were also detectable

  9. A Case of Cerebrospinal Fluid Rhinorrhoea: A Surgical Challenge

    PubMed Central

    R, Sumitha; Hari, P M; Kumar, S Ramya; Hariprasad, R

    2013-01-01

    CEREBROSPINAL FLUID rhinorrhoea is defined as the leakage of CEREBROSPINAL FLUID through the nose due to communication between nasal cavity and Sub-arachnoid space. It occurs due to breach in 4 layers – mucosa of the nose and PNS, skull base, Duramater, Subarachnoid membrane. With the advent of nasal endoscope and advancement in technology, Endoscopic Endonasal closure of CEREBROSPINAL FLUID leak has reached tremendous heights due to exact localization and precise placement of graft. In this article, we are publishing a case report of Non-traumatic normal pressure CEREBROSPINAL FLUID leak of more than 1.5cm in size which was successfully closed Endoscopically by multilayered technique PMID:23998089

  10. Cerebrospinal Fluid Biomarker Candidates for Parkinsonian Disorders

    PubMed Central

    Constantinescu, Radu; Mondello, Stefania

    2013-01-01

    The Parkinsonian disorders are a large group of neurodegenerative diseases including idiopathic Parkinson’s disease (PD) and atypical Parkinsonian disorders (APD), such as multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, and dementia with Lewy bodies. The etiology of these disorders is not known although it is considered to be a combination of genetic and environmental factors. One of the greatest obstacles for developing efficacious disease-modifying treatment strategies is the lack of biomarkers. Reliable biomarkers are needed for early and accurate diagnosis, to measure disease progression, and response to therapy. In this review several of the most promising cerebrospinal biomarker candidates are discussed. Alpha-synuclein seems to be intimately involved in the pathogenesis of synucleinopathies and its levels can be measured in the cerebrospinal fluid and in plasma. In a similar way, tau protein accumulation seems to be involved in the pathogenesis of tauopathies. Urate, a potent antioxidant, seems to be associated to the risk of developing PD and with its progression. Neurofilament light chain levels are increased in APD compared with PD and healthy controls. The new “omics” techniques are potent tools offering new insights in the patho-etiology of these disorders. Some of the difficulties encountered in developing biomarkers are discussed together with future perspectives. PMID:23346074

  11. Characterization of individual mouse cerebrospinal fluid proteomes

    SciTech Connect

    Smith, Jeffrey S.; Angel, Thomas E.; Chavkin, Charles; Orton, Daniel J.; Moore, Ronald J.; Smith, Richard D.

    2014-03-20

    Analysis of cerebrospinal fluid (CSF) offers key insight into the status of the central nervous system. Characterization of murine CSF proteomes can provide a valuable resource for studying central nervous system injury and disease in animal models. However, the small volume of CSF in mice has thus far limited individual mouse proteome characterization. Through non-terminal CSF extractions in C57Bl/6 mice and high-resolution liquid chromatography-mass spectrometry analysis of individual murine samples, we report the most comprehensive proteome characterization of individual murine CSF to date. Utilizing stringent protein inclusion criteria that required the identification of at least two unique peptides (1% false discovery rate at the peptide level) we identified a total of 566 unique proteins, including 128 proteins from three individual CSF samples that have been previously identified in brain tissue. Our methods and analysis provide a mechanism for individual murine CSF proteome analysis.

  12. "Compensated hyperosmolarity" of cerebrospinal fluid and the development of hydrocephalus.

    PubMed

    Klarica, M; Miše, B; Vladi?, A; Radoš, M; Oreškovi?, D

    2013-09-17

    Acute osmolar loading of cerebrospinal fluid within one lateral ventricle of dogs was examined as a cause of water extraction from the bloodstream and an increase in intracranial pressure. We have shown that a certain amount of (3)H?O from the bloodstream enters osmotically loaded cerebrospinal fluid significantly faster, hence causing a significant increase in intracranial pressure. The noted phenomenon in which intracranial pressure still significantly increases, but in which the hyperosmolarity of the cerebrospinal fluid is no longer present, was named "compensated hyperosmolarity". In the case of the sub-chronic application of hyperosmolar solutions into cat ventricles, we observed an increase in cerebrospinal fluid volume and a more pronounced development of hydrocephalus in the area of application, but without significant increase in intracranial pressure and without blockage of cerebrospinal fluid pathways. These results support the newly proposed hypothesis of cerebrospinal fluid hydrodynamics and the ability to develop new strategies for the treatment of cerebrospinal fluid-related diseases. PMID:23806710

  13. Three-dimensional computational prediction of cerebrospinal fluid flow in the human brain

    E-print Network

    Linninger, Andreas A.

    dynamics Cerebrospinal fluid Computational fluid dynamics Three-dimensional modeling FluidThree-dimensional computational prediction of cerebrospinal fluid flow in the human brain Brian n f o Article history: Received 19 April 2010 Accepted 12 December 2010 Keywords: Intracranial

  14. Clinical pharmacokinetics of antibacterials in cerebrospinal fluid.

    PubMed

    Di Paolo, Antonello; Gori, Giovanni; Tascini, Carlo; Danesi, Romano; Del Tacca, Mario

    2013-07-01

    In the past 20 years, an increased discrepancy between new available antibacterials and the emergence of multidrug-resistant strains has been observed. This condition concerns physicians involved in the treatment of central nervous system (CNS) infections, for which clinical and microbiological success depends on the rapid achievement of bactericidal concentrations. In order to accomplish this aim, the choice of drugs is based on their disposition toward the cerebrospinal fluid (CSF), which is influenced by the physicochemical characteristics of antibacterials. A reduced distribution into CSF has been documented for beta-lactams, especially cephalosporins and carbapenems, on the basis of their hydrophilic nature. However, they represent a cornerstone of the majority of combined therapeutic schemes for their ability to achieve bactericidal concentrations, especially in the presence of inflamed meninges. The good tolerability of beta-lactams makes possible high daily dose intensities, which may be associated with increased probability of cure. Furthermore, the adoption of continuous infusion seems to be a fruitful option. Fluoroquinolones, namely moxifloxacin, and antituberculosis drugs, together with the agents such as linezolid, reach the highest CSF/plasma concentration ratio, which is greater than 0.8, and for most of these drugs it is near 1. For all drugs that are currently used for the treatment of CNS infections, the evaluation of pharmacokinetic/pharmacodynamic parameters, on the basis of dosing regimens and their time-dependent or concentration-dependent pattern of bacterial killing, remains an important aspect of clinical investigation and medical practice. PMID:23605634

  15. Cerebrospinal Fluid HIV Escape from Antiretroviral Therapy.

    PubMed

    Ferretti, Francesca; Gisslen, Magnus; Cinque, Paola; Price, Richard W

    2015-06-01

    CNS infection is a nearly constant facet of systemic CNS infection and is generally well controlled by suppressive systemic antiretroviral therapy (ART). However, there are instances when HIV can be detected in the cerebrospinal fluid (CSF) despite suppression of plasma viruses below the clinical limits of measurement. We review three types of CSF viral escape: asymptomatic, neuro-symptomatic, and secondary. The first, asymptomatic CSF escape, is seemingly benign and characterized by lack of discernable neurological deterioration or subsequent CNS disease progression. Neuro-symptomatic CSF escape is an uncommon, but important, entity characterized by new or progressive CNS disease that is critical to recognize clinically because of its management implications. Finally, secondary CSF escape, which may be even more uncommon, is defined by an increase of CSF HIV replication in association with a concomitant non-HIV infection, as a consequence of the local inflammatory response. Understanding these CSF escape settings not only is important for clinical diagnosis and management but also may provide insight into the CNS HIV reservoir. PMID:25860317

  16. Peripheral sympathectomy and adrenal medullectomy do not alter cerebrospinal fluid norepinephrine.

    PubMed

    Peskind, E R; Raskind, M A; Wilkinson, C W; Flatness, D E; Halter, J B

    1986-03-01

    Despite a blood-brain barrier for norepinephrine, the concentration of norepinephrine in plasma and cerebrospinal fluid has been observed to be similar. This relationship between plasma and cerebrospinal fluid norepinephrine levels suggest that peripheral sympathetic neurons innervating blood vessels to brain and spinal cord may contribute significantly to cerebrospinal fluid norepinephrine levels, and questions the validity of cerebrospinal fluid norepinephrine as an index of central nervous system noradrenergic activity. We demonstrate that extensive destruction of the peripheral sympathetic nervous system and the adrenal medulla has no effect on rat cerebrospinal fluid norepinephrine. It is therefore unlikely that peripheral sources of norepinephrine contribute significantly to cerebrospinal fluid norepinephrine levels. PMID:3697700

  17. The 1H NMR Profile of Healthy Dog Cerebrospinal Fluid

    PubMed Central

    Musteata, Mihai; Nicolescu, Alina; Solcan, Gheorghe; Deleanu, Calin

    2013-01-01

    The availability of data for reference values in cerebrospinal fluid for healthy humans is limited due to obvious practical and ethical issues. The variability of reported values for metabolites in human cerebrospinal fluid is quite large. Dogs present great similarities with humans, including in cases of central nervous system pathologies. The paper presents the first study on healthy dog cerebrospinal fluid metabolomic profile using 1H NMR spectroscopy. A number of 13 metabolites have been identified and quantified from cerebrospinal fluid collected from a group of 10 mix breed healthy dogs. The biological variability as resulting from the relative standard deviation of the physiological concentrations of the identified metabolites had a mean of 18.20% (range between 9.3% and 44.8%). The reported concentrations for metabolites may be used as normal reference values. The homogeneity of the obtained results and the low biologic variability show that the 1H NMR analysis of the dog’s cerebrospinal fluid is reliable in designing and interpreting clinical and therapeutic trials in dogs with central nervous system pathologies. PMID:24376499

  18. Characterization of Transferrin Glycopeptide Structures in Human Cerebrospinal Fluid

    PubMed Central

    Brown, Kristy J.; Vanderver, Adeline; Hoffman, Eric P.; Schiffmann, Raphael; Hathout, Yetrib

    2011-01-01

    Transferrin in cerebrospinal fluid (CSF) exists as a mixture of silao and asialo glycoforms believed to originate from liver and brain respectively. We have previously shown that alteration in the asialo glycoform pattern could be an indication of certain anomalies in the central nervous system. Additionally, CSF asialo-transferrin has been shown to be a reliable marker to assess cerebrospinal leakage in head trauma. Therefore, the CSF transferrin glycoform pattern could be a useful diagnostic and prognostic tool. In this study we sought to characterize, in-depth, the transferrin glycovariants in cerebrospinal fluid using a combination of two-dimensional gel electrophoresis and high precision mass spectrometry analysis. Cerebrospinal fluid transferrin was detected as multiple spots (seven major spots) with different isoelectric points and slight shift in apparent molecular mass. High resolution (>60,000) and high accuracy (< 3 ppm error) mass spectrometry analysis revealed that each spot had a unique glycopeptide signature. MSn analysis enabled characterization of the glycan structure directly from the in-gel digested spots. The multiple spots detected for cerebrospinal fluid transferrin were mainly due to heterogeneity of di-antennary and tri-antennary glycans harboring a varying number of terminal N-acetylneuraminic acids and the existence of a high mannose and high N-acetylhexosamine glycosylated species. PMID:22408387

  19. Cerebrospinal Fluid Pressure Decreases with Older Age

    PubMed Central

    Fleischman, David; Berdahl, John P.; Zaydlarova, Jana; Stinnett, Sandra; Fautsch, Michael P.; Allingham, R. Rand

    2012-01-01

    Purpose Clinical studies implicate low cerebrospinal fluid pressure (CSFP) or a high translaminar pressure difference in the pathogenesis of primary open angle glaucoma (POAG) and normal tension glaucoma (NTG). This study was performed to examine the effect of age, sex, race and body mass index (BMI) on CSFP. Methods Electronic medical records from all patients who had a lumbar puncture (LP) performed at the Mayo Clinic from 1996–2009 were reviewed. Information including age, sex, race, height and weight, ocular and medical diagnoses, intraocular pressure (IOP) and LP opening pressure was obtained. Patients using medications or with medical diagnoses known to affect CSFP, and those who underwent neurosurgical procedures or where more than one LP was performed were excluded from analysis. Results Electronic medical records of 33,922 patients with a history of having an LP during a 13-year period (1996–2009) were extracted. Of these, 12,118 patients met all entry criteria. Relative to mean CSFP at age group 20–49 (mean 11.5±2.8 mmHg), mean CSFP declined steadily after age 50, with percent reduction of 2.5% for the 50–54 age group (mean 11.2±2.7 mmHg, p<0.002) to 26.9% for the 90–95 group (mean 8.4±2.4 mmHg, p<0.001). Females had lower CSFP than males throughout all age groups. BMI was positively and independently associated with CSFP within all age groups. Conclusion There is a sustained and significant reduction of CSFP with age that begins in the 6th decade. CSFP is consistently lower in females. BMI is positively and independently associated with CSFP in all age groups. The age where CSFP begins to decline coincides with the age where the prevalence of POAG increases. These data support the hypothesis that reduced CSFP may be a risk factor for POAG and may provide an explanation for the mechanism that underlies the age-related increase in the prevalence of POAG and NTG. PMID:23300737

  20. Diffusion of intramuscular ketoprofen into the cerebrospinal fluid

    Microsoft Academic Search

    P. Netter; F. Lapicque; B. Bannwarth; J. N. Tamisier; P. Thomas; R. J. Royer

    1985-01-01

    Serum and cerebrospinal fluid (CSF) concentrations of ketoprofen have been measured in 36 patients hospitalised for sciatica. Diagnostic lumbar puncture was done 15 min to 13 h after a single 100 mg intramuscular dose of ketoprofen. Serum and CSF were sampled at the same time. Free serum concentrations were determined by equilibrium dialysis. Total and free concentrations were assayed by

  1. Entamoeba histolytica meningoencephalitis diagnosed by trophozoites in cerebrospinal fluid.

    PubMed

    Goh, L M L; Marrone, J R

    2013-10-01

    Entamoeba histolytica meningoencephalitis has not been described in the modern literature, which is distinct from that caused by free-living amoebae. We report the first case of E. histolytica meningoencephalitis without liver or brain abscesses. Cerebrospinal fluid revealed 2 + very motile trophozoites. Our patient was successfully treated with intravenous metronidazole. PMID:25356319

  2. Reporting Cerebrospinal Fluid Data: Knowledge Base and Interpretation Software

    Microsoft Academic Search

    Hansotto Reiber; Markus Otto; Christian Trendelenburg; Arno Wormek

    2001-01-01

    The compilation of cerebrospinal fluid (CSF) patient data together with a graphic display of immunoglob- ulin patterns in a single CSF report has two main ad- vantages: analytical and clinical plausibility control of a complex set of data improves quality assessment and allows improved clinical specificity and sensitivity for recognition of disease-relat ed \\

  3. Increased Cerebrospinal Fluid Tau Protein in Multiple Sclerosis

    Microsoft Academic Search

    Elisabeth Kapaki; George P. Paraskevas; Maria Michalopoulou; Konstantinos Kilidireas

    2000-01-01

    Axonal damage is now being recognized as a common finding in multiple sclerosis (MS) lesions and a cause of irreversible neurological damage. Attempts to identify markers of early axonal damage are of great significance. This prompted us to examine the microtubule-associated protein tau in the cerebrospinal fluid (CSF) of patients with MS vs. controls. Tau was measured by double antibody

  4. Cerebrospinal Fluid Cytokine Levels and Cognitive Impairment in Cerebral Malaria

    PubMed Central

    John, Chandy C.; Panoskaltsis-Mortari, Angela; Opoka, Robert O.; Park, Gregory S.; Orchard, Paul J.; Jurek, Anne M.; Idro, Richard; Byarugaba, Justus; Boivin, Michael J.

    2008-01-01

    Cerebrospinal fluid (CSF) and serum levels of 12 cytokines or chemokines important in central nervous system (CNS) infections were measured in 76 Ugandan children with cerebral malaria (CM) and 8 control children. As compared with control children, children with cerebral malaria had higher cerebrospinal fluid levels of interleukin (IL)-6, CXCL-8/IL-8, granulocyte-colony stimulating factor (G-CSF), tumor necrosis factor-? (TNF-?), and IL-1 receptor antagonist. There was no correlation between cerebrospinal and serum cytokine levels for any cytokine except G-CSF. Elevated cerebrospinal fluid but not serum TNF-? levels on admission were associated with an increased risk of neurologic deficits 3 months later (odds ratio 1.55, 95% CI: 1.10, 2.18, P = 0.01) and correlated negatively with age-adjusted scores for attention (Spearman rho, -0.34, P = 0.04) and working memory (Spearman rho, -0.32, P = 0.06) 6 months later. In children with cerebral malaria, central nervous system TNF-? production is associated with subsequent neurologic and cognitive morbidity. PMID:18256412

  5. Sleep deprivation increases oleoylethanolamide in human cerebrospinal fluid

    Microsoft Academic Search

    Dagmar Koethe; Daniela Schreiber; Andrea Giuffrida; Christian Mauss; Johannes Faulhaber; Bernd Heydenreich; Martin Hellmich; Rudolf Graf; Joachim Klosterkötter; Daniele Piomelli; F. Markus Leweke

    2009-01-01

    This study investigated the role of two fatty acid ethanolamides, the endogenous cannabinoid anandamide and its structural\\u000a analog oleoylethanolamide in sleep deprivation of human volunteers. Serum and cerebrospinal fluid (CSF) samples were obtained\\u000a from 20 healthy volunteers before and after a night of sleep deprivation with an interval of about 12 months. We found increased\\u000a levels of oleoylethanolamide in CSF (P = 0.011)

  6. Myelin basic protein in cerebrospinal fluid from children

    Microsoft Academic Search

    A. Kohlschütter

    1978-01-01

    Forty-one cerebrospinal fluid (CSF) specimens from children were investigated with a radioimmunoassay for their content of myelin basic protein (BP). Eight specimens were regarded as BP-positive (BP?1.0 ng\\/ml). Twenty-nine were BP-negative and 4 could not be analyzed because of an excessive protein content. The BP-positive samples were from 6 children with evidence of severe acute brain damage leading to death

  7. Entry of diazepam and its major metabolite into cerebrospinal fluid

    Microsoft Academic Search

    David J. Greenblatt; Hermann R. Ochs; Brian L. Lloyd

    1980-01-01

    Five dogs received a single 1.0 mg\\/kg dose of diazepam (DZ) IV. Concentrations of DZ and its major metabolite desmethyldiazepam (DMDZ) were simultaneously measured in plasma and cisternal cerebrospinal fluid (CSF) for up to 8 h after the dose by electron-capture gas-liquid chromatography. DZ was rapidly eliminated from plasma (half-life 0.3–1.3 h); DZ disappearance was mirrored by formation of DMDZ,

  8. Cerebrospinal fluid immunoglobulins and complement in meningococcal meningitis

    Microsoft Academic Search

    H C Whittle; B M Greenwood

    1977-01-01

    Cerebrospinal fluid (CSF) immunoglobulins (IgA, IgG, IgM) were measured in 107 patients with meningococcal meningitis. Levels were correlated significantly with CSF total protein, and both CSF immunoglobulin and protein increased with age. C3 was measured in the CSF of 38 patients and was also closely correlated with the CSF protein level. C3 breakdown products were found in all six CSFs

  9. Summary of cerebrospinal fluid routine parameters in neurodegenerative diseases

    Microsoft Academic Search

    Sarah Jesse; Johannes Brettschneider; Sigurd D. Süssmuth; Bernhard G. Landwehrmeyer; Christine A. F. von Arnim; Albert C. Ludolph; Hayrettin Tumani; Markus Otto

    2011-01-01

    In neurodegenerative diseases, cerebrospinal fluid analysis (CSF) is predominantly performed to exclude inflammatory diseases\\u000a and to perform a risk assessment in dementive disorders by measurement of tau proteins and amyloid beta peptides. However,\\u000a large scale data on basic findings of CSF routine parameters are generally lacking. The objective of the study was to define\\u000a a normal reference spectrum of routine

  10. Glycosphingolipids in the cerebrospinal fluid of patients with multiple sclerosis

    Microsoft Academic Search

    Nobuyuki Miyatani; Megumi Saito; Toshio Ariga; Hiide Yoshino; Robert K. Yu

    1990-01-01

    Glycosphingolipids in cerebrospinal fluid (CSF) of individual patients with multiple sclerosis (MS) were analyzed using a\\u000a glycolipid-overlay technique. The ganglioside composition of CSF of non-MS patients was characterized by an abundance of polysialo\\u000a species, including GT1b and GQ1b. This pattern is completely different from that of human white or gray matter, in which mono-\\u000a and disialogangliosides predominate. Increased levels of

  11. ANTIBODIES TO SCHISTOSOMA MANSONI IN HUMAN CEREBROSPINAL FLUID

    Microsoft Academic Search

    ISIS F. MAGALHÃES-SANTOS; DENISE C. LEMAIRE; ANTONIO S. ANDRADE-FILHO; ARISTIDES C. QUEIROZ; OTÁVIO M. CARVALHO; M. A. CARMO; ISADORA C. SIQUEIRA; DÉBORA M. ANDRADE; MICHELY F. REGO; ANA PAULA T. GUEDES; MITERMAYER G. REIS

    Cerebrospinal fluid (CSF) and serum samples from patients suspected of having neuroschistosomiasis (NS) were evaluated by an enzyme-linked immunosorbent assay. Monoclonal antibodies of various immunoglobulin isotypes (IgM, IgA, IgE, total IgG, IgG1, IgG2, IgG3, and IgG4) were used to detect antibodies against Schistosoma mansoni soluble egg antigen (SEA) and soluble worm adult preparation (SWAP). Of the 83 CSF samples tested,

  12. Methylmercury increases S100B content in rat cerebrospinal fluid

    Microsoft Academic Search

    M. Farina; V. Cereser; L. V. Portela; A. Mendez; L. O. Porciúncula; J. Fornaguera; C. A. Gonçalves; S. T. Wofchuk; J. B. T. Rocha; D. O. Souza

    2005-01-01

    S100B, a calcium binding protein physiologically produced and released by astrocytes, has been used as a peripheral marker of brain damage. Here, we investigated the effects of subcutaneous injections of methylmercury chloride (MeHg–5mg\\/kg), an environmental neurotoxicant, on S100B protein content in cerebrospinal fluid (CSF) of adult rats. In addition, the performance of animals in an open field (number of squares

  13. Disposition of ethmozine in cerebrospinal fluid and plasma of rabbits

    Microsoft Academic Search

    K. Chan; J. M. Yang; M. K. Wai; W. D. Jiang

    1989-01-01

    Summary  The concentration — time profiles of ethmozine, a newly introduced anti-arrhythmic drug, in the cerebrospinal fluid (CSF)\\u000a and plasma of six rabbits (New Zealand white rabbits of both sexes, 4.0–5.0 Kg) were studied after intravenous bolus administration.\\u000a CSF samples at various intervals were obtained while the animal was lightly anaesthetized with intravenous thiopentone (40\\u000a mg Kg?1 ) and blood samples

  14. Evaluation and Management of Spontaneous Temporal Bone Cerebrospinal Fluid Leaks

    PubMed Central

    Pappas, Dennis G.; Hoffman, Ronald A.; Holliday, Roy A.; Hammerschlag, Paul E.; Pappas, Dennis G.; Swaid, Swaid N.

    1995-01-01

    Spontaneous temporal bone cerebrospinal fluid leak may be defined as a leak without an apparent precipitating cause. These transdural fistulas occur rarely, and diagnosis is predicated upon a high index of suspicion. Leaks have been reported through both middle and posterior fossa defects, although the vast majority involve the middle fossa plate. In a previous study we reported 7 cases of spontaneous temporal bone cerebrospinal fluid leaks, all involving the middle fossa tegmen. Upon further review of these cases and 5 previously unreported cases, the defect was localized to the tegmen tympani in 9 of the total 12 cases. Diagnostic methods are discussed, with the importance of high-resolution computed tomography stressed. The role of contrast cisternography is also evaluated. An outline for surgical management is presented based upon residual hearing and defect location and accessibility. A transmastoid procedure offers the advantage of visualization of both the middle and posterior fossa plates, and this approach can be supplemented with an obliterative procedure when indicated. The middle fossa approach provides optimal exposure of the tegmen plate with less likelihood of ossicular injury when dealing with tegmen tympani defects. Adjuncts to surgical therapy include intrathecal fluorescein dye and continuous postoperative lumbar cerebrospinal fluid drainage. ImagesFigure 1Figure 2Figure 3Figure 4 PMID:17171151

  15. Quantitative proteomics comparison of arachnoid cyst fluid and cerebrospinal fluid collected perioperatively from arachnoid cyst patients

    PubMed Central

    2013-01-01

    Background There is little knowledge concerning the content and the mechanisms of filling of arachnoid cysts. The aim of this study was to compare the protein content of arachnoid cysts and cerebrospinal fluid by quantitative proteomics to increase the understanding of arachnoid cysts. Methods Arachnoid cyst fluid and cerebrospinal fluid from five patients were analyzed by quantitative proteomics in two separate experiments. In a label-free experiment arachnoid cyst fluid and cerebrospinal fluid samples from individual patients were trypsin digested and analyzed by Orbitrap mass spectrometry in a label-free manner followed by data analysis using the Progenesis software. In the second proteomics experiment, a patient sample pooling strategy was followed by MARS-14 immunodepletion of high abundant proteins, trypsin digestion, iTRAQ labelling, and peptide separation by mix-phase chromatography followed by Orbitrap mass spectrometry analysis. The results from these analyzes were compared to previously published mRNA microarray data obtained from arachnoid membranes. Results We quantified 348 proteins by the label-free individual patient approach and 1425 proteins in the iTRAQ experiment using a pool from five patients of arachnoid cyst fluid and cerebrospinal fluid. This is by far the largest number of arachnoid cyst fluid proteins ever identified, and the first large-scale quantitative comparison between the protein content of arachnoid cyst fluid and cerebrospinal fluid from the same patients at the same time. Consistently in both experiment, we found 22 proteins with significantly increased abundance in arachnoid cysts compared to cerebrospinal fluid and 24 proteins with significantly decreased abundance. We did not observe any molecular weight gradient over the arachnoid cyst membrane. Of the 46 proteins we identified as differentially abundant in our study, 45 were also detected from the mRNA expression level study. None of them were previously reported as differentially expressed. We did not quantify any of the proteins corresponding to gene products from the ten genes previously reported as differentially abundant between arachnoid cysts and control arachnoid membranes. Conclusions From our experiments, the protein content of arachnoid cyst fluid and cerebrospinal fluid appears to be similar. There were, however, proteins that were significantly differentially abundant between arachnoid cyst fluid and cerebrospinal fluid. This could reflect the possibility that these proteins are affected by the filling mechanism of arachnoid cysts or are shed from the membranes into arachnoid cyst fluid. Our results do not support the proposed filling mechanisms of oncotic pressure or valves. PMID:23628075

  16. Cerebrospinal Fluid Flow Dynamics in the Central Nervous System BRIAN SWEETMAN and ANDREAS A. LINNINGER

    E-print Network

    Linninger, Andreas A.

    -MRI is the basis for developing computational fluid dynamic models that help quantify intracranial dynamics, Intracranial dynamics, Pressure wave speed, Computational fluid dynamics. INTRODUCTION CineCerebrospinal Fluid Flow Dynamics in the Central Nervous System BRIAN SWEETMAN and ANDREAS A

  17. Extremely rare complications in cerebrospinal fluid shunt operations.

    PubMed

    Surchev, J; Georgiev, K; Enchev, Y; Avramov, R

    2002-06-01

    The cerebrospinal fluid shunt operation, from its first realization in 1908 by Kausch till our days, is still of a significant importance for the long-term treatment of the internal hydrocephalus. Well known are many complications connected with the use of the valve systems (malfunction, infectious, overdrainage, secondary craniosynostosis and etc.). For a period of 17 years (1984-2000) at the Clinic of Pediatric Neurosurgery, Department of Neurosurgery, Sofia Medical University, 414 cerebrospinal fluid shunt operations were performed on children. 216 were drained to the right atrium of the heart, 198 to the peritoneal cavity. They were followed up by catamnesis until the year 2001. The authors describe 2 extremely rare cases with post-shunt complication as a result of a malfunction of the valve system, owing to a migration of the distal catheter: 1) in the anus; 2) in the urethra. In the first case the distal catheter perforated the colon transversum and by the way of the intestines went out through the anus. In the second case the distal catheter protruded out of the body through the bladder and the urethra. Their clinical appearance, the diagnostic examinations and the operative treatment are shown. PMID:12232559

  18. Ganciclovir penetrates into the cerebrospinal fluid of an infant with congenital cytomegalovirus infection.

    PubMed

    Natale, Fabio; Bizzarri, Bianca; Cardi, Veronica; Gaeta, Aurelia; Villani, Paola; Liuzzi, Giuseppina; De Curtis, Mario

    2015-01-01

    Currently, there is no evidence whether ganciclovir, or its oral prodrug valganciclovir, penetrates into the cerebrospinal fluid of human infants treated for congenital cytomegalovirus infection. Here, we report a case study providing evidence that ganciclovir, administered as valganciclovir, reaches the infant's cerebrospinal fluid when used at the currently recommended dose for congenital cytomegalovirus infection. PMID:25888518

  19. Fibrin degradation products in the serum and cerebrospinal fluid of patients with group A meningococcal meningitis

    Microsoft Academic Search

    M. J. Brueton; P. Tugwell; H. C. Whittle; B. M. Greenwood

    1974-01-01

    Forty-one patients suffering from group A meningococcal meningitis in an area within the epidemic meningococcal belt of tropical West Africa were studied. The serum of only two of these patients contained fibrin degradation products (FDPs). The cerebrospinal fluid of 21 of these cases was also examined for FDPs, which were present in 13. Their presence in the cerebrospinal fluid was

  20. Does the secretion and circulation of the cerebrospinal fluid really exist?

    Microsoft Academic Search

    D. Oreskovic; M. Klarica; M. Vukic

    2001-01-01

    The secretion and circulation of cerebrospinal fluid have been studied in anaesthetized cats by means of a plastic cannula introduced into the aqueduct of Sylvius and by inspection of free escape of cerebrospinal fluid out of the end of the cannula. The fact that during the 120-minute period of observation not a single drop of CSF escaped out of the

  1. Cerebrospinal fluid neurohypophysial peptides in benign intracranial hypertension.

    PubMed Central

    Seckl, J; Lightman, S

    1988-01-01

    The cerebrospinal fluid (CSF) concentrations of arginine vasopressin (AVP) and oxytocin (OT) were investigated both in patients with benign intracranial hypertension and in age and sex matched controls. Twenty eight lumbar punctures were performed on 15 patients with benign intracranial hypertension as part of their routine investigation and therapy. All patients had raised intracranial pressure (27.4, SE 1.7 cm.CSF). CSF AVP levels were significantly elevated in benign intracranial hypertension (2.1, SE 0.3 pmol/l) compared with controls (0.7, SE 0.1 pmol/l, p less than 0.001) but CSF OT concentrations were similar in both groups. CSF osmolality and plasma AVP and osmolality were identical in patients and controls. There was no correlation between CSF AVP concentration and intracranial pressure. The selective elevation of AVP in CSF may be of importance in the pathogenesis of raised intracranial pressure in benign intracranial hypertension. PMID:3221220

  2. Cerebrospinal fluid biomarkers of Alzheimer's disease in healthy elderly.

    PubMed

    Randall, Catherine; Mosconi, Lisa; de Leon, Mony; Glodzik, Lidia

    2013-01-01

    Numerous studies have shown that Alzheimer's Disease (AD) pathology begins before the onset of clinical symptoms. Because therapies are likely to be more effective if they are implemented early in the disease progression, it is necessary to identify reliable biomarkers to detect AD pathology in the early stages of the disease, ideally in presymptomatic individuals. Recent research has identified three candidate cerebrospinal fluid (CSF) biomarkers that reflect AD pathology: amyloid beta, total tau protein (t-tau), and tau protein phosphorylated at AD-specific epitopes (p-tau). They are useful in supporting the AD diagnosis and have predictive value for AD when patients are in the stage of mild cognitive impairment (MCI). However, their predictive utility in cognitively healthy subjects is still being evaluated. We conducted a review of studies published between 1993 and 2011 and summarized their findings on the role of CSF biomarkers for AD in healthy elderly. PMID:23747874

  3. On Chip Analysis of CNS Lymphoma in Cerebrospinal Fluid

    PubMed Central

    Turetsky, Anna; Lee, Kyungheon; Song, Jun; Giedt, Randy J.; Kim, Eunha; Kovach, Alexandra E.; Hochberg, Ephraim P.; Castro, Cesar M.; Lee, Hakho; Weissleder, Ralph

    2015-01-01

    Molecular profiling of central nervous system lymphomas in cerebrospinal fluid (CSF) samples can be challenging due to the paucicellular and limited nature of the samples. Presented herein is a microfluidic platform for complete CSF lymphoid cell analysis, including single cell capture in sub-nanoliter traps, and molecular and chemotherapeutic response profiling via on-chip imaging, all in less than one hour. The system can detect scant lymphoma cells and quantitate their kappa/lambda immunoglobulin light chain restriction patterns. The approach can be further customized for measurement of additional biomarkers, such as those for differential diagnosis of lymphoma subtypes or for prognosis, as well as for imaging exposure to experimental drugs. PMID:26000053

  4. Cerebrospinal fluid proteome of patients with acute Lyme disease.

    PubMed

    Angel, Thomas E; Jacobs, Jon M; Smith, Robert P; Pasternack, Mark S; Elias, Susan; Gritsenko, Marina A; Shukla, Anil; Gilmore, Edward C; McCarthy, Carol; Camp, David G; Smith, Richard D; Warren, H Shaw

    2012-10-01

    During acute Lyme disease, bacteria can disseminate to the central nervous system (CNS), leading to the development of meningitis and other neurologic symptoms. Here we have analyzed pooled cerebrospinal fluid (CSF) allowing a deep view into the proteome for patients diagnosed with early disseminated Lyme disease and CSF inflammation. Additionally, we analyzed individual patient samples and quantified differences in protein abundance employing label-free quantitative mass spectrometry-based methods. We identified 108 proteins that differ significantly in abundance in patients with acute Lyme disease from controls. Comparison between infected patients and control subjects revealed differences in proteins in the CSF associated with cell death localized to brain synapses and others that likely originate from brain parenchyma. PMID:22900834

  5. The oxysterol and cholestenoic acid profile of mouse cerebrospinal fluid

    PubMed Central

    Crick, Peter J.; Beckers, Lien; Baes, Myriam; Van Veldhoven, Paul P.; Wang, Yuqin; Griffiths, William J.

    2015-01-01

    Oxysterols and cholestenoic acids are oxidised forms of cholesterol with a host of biological functions. The possible roles of oxysterols in various neurological diseases makes the analysis of these metabolites in the central nervous system of particular interest. Here, we report the identification and quantification of a panel of twelve sterols in mouse cerebrospinal fluid (CSF) using liquid chromatography–mass spectrometry exploiting enzyme assisted derivatisation for sterol analysis technology. We found low levels of oxysterols and cholestenoic acids in CSF in the range of 5 pg/mL–2.6 ng/mL. As found in man, these concentrations are one to two orders of magnitude lower than in plasma. PMID:25759118

  6. Cerebrospinal Fluid Aquaporin-4 Antibody Levels in Neuromyelitis Optica Attacks

    PubMed Central

    Sato, Douglas Kazutoshi; Callegaro, Dagoberto; de Haidar Jorge, Frederico M; Nakashima, Ichiro; Nishiyama, Shuhei; Takahashi, Toshiyuki; Simm, Renata Faria; Apostolos-Pereira, Samira Luisa; Misu, Tatsuro; Steinman, Lawrence; Aoki, Masashi; Fujihara, Kazuo

    2014-01-01

    To elucidate immunopathogenetic roles of aquaporin-4 antibodies in the cerebrospinal fluid (CSF) of neuromyelitis optica spectrum disorders (NMOSD), we analyzed aquaporin-4 antibody titers, cellular and inflammatory markers in the CSF collected from 11 aquaporin-4 antibody seropositive patients. The CSF aquaporin-4 antibody levels during attacks (but not in sera) closely correlated with pleocytosis, inflammatory cytokines including interleukin-6 that can regulate antibody-producing plasmablasts, and glial fibrillary acidic protein levels in the CSF. The amount of aquaporin-4 antibodies present in the central nervous system may have therapeutic implications, as it is associated with astrocyte injury and inflammatory responses during NMOSD attacks. Ann Neurol 2014;76:305–309 PMID:24977390

  7. The oxysterol and cholestenoic acid profile of mouse cerebrospinal fluid.

    PubMed

    Crick, Peter J; Beckers, Lien; Baes, Myriam; Van Veldhoven, Paul P; Wang, Yuqin; Griffiths, William J

    2015-07-01

    Oxysterols and cholestenoic acids are oxidised forms of cholesterol with a host of biological functions. The possible roles of oxysterols in various neurological diseases makes the analysis of these metabolites in the central nervous system of particular interest. Here, we report the identification and quantification of a panel of twelve sterols in mouse cerebrospinal fluid (CSF) using liquid chromatography-mass spectrometry exploiting enzyme assisted derivatisation for sterol analysis technology. We found low levels of oxysterols and cholestenoic acids in CSF in the range of 5pg/mL-2.6ng/mL. As found in man, these concentrations are one to two orders of magnitude lower than in plasma. PMID:25759118

  8. Orbital cerebrospinal fluid accumulation after complicated pterional-orbitozygomatic craniotomy.

    PubMed

    Yoon, Michael K; Piluek, Wachirapon Jordan; Ruggiero, Jason P; McDermott, Michael W; McCulley, Timothy J

    2014-12-01

    We describe 2 patients who developed postoperative orbital cerebrospinal fluid (CSF) collection after orbitozygomatic pterional craniotomy. An 18-year-old woman underwent exploratory pterional-orbitozygomatic craniotomy. Five days postoperatively, after removal of a lumbar drain, proptosis and a compressive optic neuropathy developed. Computed tomography demonstrated a CSF collection contiguous with the craniotomy site. Resolution followed percutaneous aspiration and replacement of the lumbar drain. A 57-year-old woman underwent a pterional-orbitozygomatic craniotomy for removal of a left anterior clinoid meningioma, complicated by a large left hemorrhagic stroke requiring decompressive hemicraniectomy. Extracranial CSF collections accumulated in both the orbit and subgaleal spaces. Resolution followed placement of an external ventricular drain. Based on these cases, the mechanism seems to be the combination of iatrogenic formation of a communication with the subarachnoid space and elevated intracranial pressure. Resolution was achieved by normalizing intracranial pressure. PMID:24699141

  9. Cerebrospinal fluid pulse waveform as an indicator of cerebral autoregulation.

    PubMed

    Portnoy, H D; Chopp, M; Branch, C; Shannon, M B

    1982-05-01

    Systems analysis of the systemic arterial (SAPW), cerebrospinal fluid (CSFPW), and sagittal sinus (SSPW) pulse waves was carried out in 13 dogs during hypercapnia (5% CO2), intracranial normotension (inhalation of 100% O2), and intracranial hypertension (inhalation of 100% O2 plus an intraventricular infusion). Power amplitude and phase spectra were determined for each wave, and the power amplitude and phase transfer functions calculated between the cerebrospinal fluid (CSF) pressure and systemic arterial pressures, and between the sagittal sinus pressure and CSF pressure. The study indicates that the CSFPW and SSPW were virtually identical when impedance between the cerebral veins and sagittal sinus was minimal, which argues that the CSF pulse was derived from the cerebral venous bed. During inhalation of 100% O2, transmission of the SAPW across the precapillary resistance vessels into the cerebral venous pulse (as represented by the CSFPW) was nonlinear, while transmission across the lateral lacunae into the sagittal sinus was linear. During intracranial hypertension, wave transmission across the precapillary resistance vessels was linear, and across the lateral lacunae was nonlinear. During hypercapnia, wave transmission across the precapillary resistance vessels and the lateral lacunae was linear. When the wave transmission was nonlinear, there was also suppression in transmission of the lower harmonics, particularly the fundamental frequency, and a more positive phase transfer function, suggesting an inertial effect or decrease in acceleration of the pulse. Conversion from a nonlinear to linear transmission across the precapillary resistance vessels is evidence of loss of vasomotor tone, and is accompanied by rounding of the CSFPW. A vascular model which encompasses the above data and is based on flow in collapsible tubes and changes in vasomotor tone is posited to explain control of pulsatile flow and pulse waveform changes in the cerebrovascular bed. The model helps to clarify the strong interrelationship between intracranial pressure, cerebral blood flow, and cerebral autoregulation. PMID:7069479

  10. Cerebrospinal Fluid Particles in Alzheimer Disease and Parkinson Disease.

    PubMed

    Yang, Yue; Keene, C Dirk; Peskind, Elaine R; Galasko, Douglas R; Hu, Shu-Ching; Cudaback, Eiron; Wilson, Angela M; Li, Ge; Yu, Chang-En; Montine, Kathleen S; Zhang, Jing; Baird, Geoffrey S; Hyman, Bradley T; Montine, Thomas J

    2015-07-01

    Human cerebrospinal fluid (CSF) contains diverse lipid particles, including lipoproteins that are distinct from their plasma counterparts and contain apolipoprotein (apo) E isoforms, apoJ, and apoAI, and extracellular vesicles, which can be detected by annexin V binding. The aim of this study was to develop a method to quantify CSF particles and evaluate their relationship to aging and neurodegenerative diseases. We used a flow cytometric assay to detect annexin V-, apoE-, apoAI-, apoJ-, and amyloid (A) ?42-positive particles in CSF from 131 research volunteers who were neurologically normal or had mild cognitive impairment (MCI), Alzheimer disease (AD) dementia, or Parkinson disease. APOE ?4/?4 participants had CSF apoE-positive particles that were more frequently larger but at an 88% lower level versus those in APOE ?3/?3 or APOE ?3/?4 patients; this finding was reproduced in conditioned medium from mouse primary glial cell cultures with targeted replacement of apoE. Cerebrospinal fluid apoE-positive and ?-amyloid (A?42)-positive particle concentrations were persistently reduced one-third to one-half in middle and older age subjects; apoAI-positive particle concentration progressively increased approximately 2-fold with age. Both apoAI-positive and annexin V-positive CSF particle levels were reduced one-third to one-half in CSF of MCI and/or AD dementia patients versus age-matched controls. Our approach provides new methods to investigate CNS lipid biology in relation to neurodegeneration and perhaps develop new biomarkers for diagnosis or treatment monitoring. PMID:26083568

  11. Embryonic blood-cerebrospinal fluid barrier formation and function

    PubMed Central

    Bueno, David; Parvas, Maryam; Hermelo, Ismaïl; Garcia-Fernàndez, Jordi

    2014-01-01

    During embryonic development and adult life, brain cavities and ventricles are filled with cerebrospinal fluid (CSF). CSF has attracted interest as an active signaling medium that regulates brain development, homeostasis and disease. CSF is a complex protein-rich fluid containing growth factors and signaling molecules that regulate multiple cell functions in the central nervous system (CNS). The composition and substance concentrations of CSF are tightly controlled. In recent years, it has been demonstrated that embryonic CSF (eCSF) has a key function as a fluid pathway for delivering diffusible signals to the developing brain, thus contributing to the proliferation, differentiation and survival of neural progenitor cells, and to the expansion and patterning of the brain. From fetal stages through to adult life, CSF is primarily produced by the choroid plexus. The development and functional activities of the choroid plexus and other blood–brain barrier (BBB) systems in adults and fetuses have been extensively analyzed. However, eCSF production and control of its homeostasis in embryos, from the closure of the anterior neuropore when the brain cavities become physiologically sealed, to the formation of the functional fetal choroid plexus, has not been studied in as much depth and remains open to debate. This review brings together the existing literature, some of which is based on experiments conducted by our research group, concerning the formation and function of a temporary embryonic blood–CSF barrier in the context of the crucial roles played by the molecules in eCSF. PMID:25389383

  12. Differentiation of communicating hydrocephalus and presenile dementia by continuous recording of cerebrospinal fluid pressure.

    PubMed Central

    Hartmann, A; Alberti, E

    1977-01-01

    Continuous monitoring of the cerebrospinal fluid pressure and observation of the pressure during intrathecal infusion of normal saline at two rates were performed in patients with communicating hydrocephalus and cerebral atrophy of other causes. Constant or temporarily increased cerebrospinal fluid pressure was observed only in communicating hydrocephalus. Reduction of intracranial pressure by a ventriculoatrial shunt was associated with clinical improvement. The intrathecal infusion test was capable of detecting reduced absorption of cerebrospinal fluid if more than one infusion rate was employed. Using both tests it is easier to determine which patients with communicating hydrocephalus should be treated with a shunt operation. Images PMID:915506

  13. Review of "Proteins of the Cerebrospinal Fluid" (2nd Edition) by Edward J. Thompson

    PubMed Central

    Connor, James R

    2007-01-01

    This book on cerebrospinal fluid (CSF) proteins is primarily focused on immunoglobulins. The book was written as an extension of a meeting on multiple sclerosis to provide a more extensive consideration of the CSF.

  14. Cytomegalovirus Antibody in Cerebrospinal Fluid of Schizophrenic Patients Detected by Enzyme Immunoassay

    NASA Astrophysics Data System (ADS)

    Fuller Torrey, E.; Yolken, Robert H.; Winfrey, C. Jack

    1982-05-01

    By means of enzyme immunoassay techniques to detect the presence of antibody to cytomegalovirus, the cerebrospinal fluid of 178 patients with schizophrenia, 17 patients with bipolar disorders, and 11 other psychiatric patients was compared with that of 79 neurological patients and 41 normal control subjects. The cerebrospinal fluid of 20 of the schizophrenic patients and 3 of the patients with bipolar disorders showed significant increases in immunoglobulin M antibody to cytomegalovirus; no difference was found in patients on or off psychotropic medications.

  15. Embryonic cerebrospinal fluid in brain development: neural progenitor control

    PubMed Central

    Gato, Angel; Alonso, M. Isabel; Martín, Cristina; Carnicero, Estela; Moro, José Antonio; De la Mano, Aníbal; Fernández, José M. F.; Lamus, Francisco; Desmond, Mary E.

    2014-01-01

    Due to the effort of several research teams across the world, today we have a solid base of knowledge on the liquid contained in the brain cavities, its composition, and biological roles. Although the cerebrospinal fluid (CSF) is among the most relevant parts of the central nervous system from the physiological point of view, it seems that it is not a permanent and stable entity because its composition and biological properties evolve across life. So, we can talk about different CSFs during the vertebrate life span. In this review, we focus on the CSF in an interesting period, early in vertebrate development before the formation of the choroid plexus. This specific entity is called “embryonic CSF.” Based on the structure of the compartment, CSF composition, origin and circulation, and its interaction with neuroepithelial precursor cells (the target cells) we can conclude that embryonic CSF is different from the CSF in later developmental stages and from the adult CSF. This article presents arguments that support the singularity of the embryonic CSF, mainly focusing on its influence on neural precursor behavior during development and in adult life. PMID:25165044

  16. Cerebrospinal Fluid Proteome of Patients with Acute Lyme Disease

    SciTech Connect

    Angel, Thomas E.; Jacobs, Jon M.; Smith, Robert P.; Pasternack, Mark S.; Elias, Susan; Gritsenko, Marina A.; Shukla, Anil K.; Gilmore, Edward C.; McCarthy, Carol; Camp, David G.; Smith, Richard D.

    2012-10-05

    Acute Lyme disease results from transmission of and infection by the bacterium Borrelia burgdorferi following a tick bite. During acute infection, bacteria can disseminate to the central nervous system (CNS) leading to the development of Lyme meningitis. Here we have analyzed pooled cerebrospinal fluid (CSF) allowing for a deep view into the proteome for a cohort of patients with early-disseminated Lyme disease and CSF inflammation leading to the identification of proteins that reflect host responses, which are distinct for subjects with acute Lyme disease. Additionally, we analyzed individual patient samples and quantified changes in protein abundance employing label-free quantitative mass spectrometry based methods. The measured changes in protein abundances reflect the impact of acute Lyme disease on the CNS as presented in CSF. We have identified 89 proteins that differ significantly in abundance in patients with acute Lyme disease. A number of the differentially abundant proteins have been found to be localized to brain synapse and thus constitute important leads for better understanding of the neurological consequence of disseminated Lyme disease.

  17. Pharmacokinetics of florfenicol in cerebrospinal fluid and plasma of calves.

    PubMed Central

    de Craene, B A; Deprez, P; D'Haese, E; Nelis, H J; Van den Bossche, W; De Leenheer, P

    1997-01-01

    Florfenicol, a fluorinated analog of thiamphenicol, is of great value in veterinary infectious diseases that formerly responded favorably to chloramphenicol. In view of the treatment of meningitis in calves, we studied its pharmacokinetics in the cerebrospinal fluid (CSF) and plasma of six animals. To this end, a new high-performance liquid chromatography method was developed which, unlike previous ones, uses solid-phase instead of double-phase extraction to isolate the drug. After a single intravenous dose of 20 mg/kg of body weight, a maximum concentration in CSF of 4.67 +/- 1.51 microg/ml (n = 6) was reached, with a mean residence time of 8.7 h. The decline of florfenicol in both CSF and plasma fitted a biexponential model with elimination half-lives of 13.4 and 3.2 h, respectively. Florfenicol penetrated well into CSF, as evidenced from an availability of 46% +/- 3% relative to plasma. The levels remained above the MIC for Haemophilus somnus over a 20-h period. Our results provide evidence indicating the effectiveness of florfenicol in the treatment of bacterial meningitis of calves. PMID:9303399

  18. [Cerebrospinal fluid markers in early diagnosis of Alzheimer dementia].

    PubMed

    Wiltfang, Jens

    2015-04-01

    Cerebrospinal fluid-based neurochemical dementia diagnostics (CSF-NDD) is meanwhile validated on S3 evidence level and international dementia guidelines like those of the German neuropsychiatric associations (DGPPN, DGN; http://www.DGPPN.de) recommend CSF-NDD for the improved early and differential diagnostics of multigenetic (sporadic) Alzheimer's Dementia (AD). CSF-NDD does also offer a predictive diagnosis of incipient AD for high-risk patients when they are still within the prodromal stage of mild cognitive impairment (MCI). But since currently no (secondary) preventive therapy of AD is available, the use of CSF-NDD for the predictive molecular diagnosis of AD is not recommended by the latter guidelines. However, molecular diagnostics of preclinical AD by CSF-NDD and/or [18F]Amyloid-PET has meanwhile gained high clinical relevance for therapeutic clinical research, as this novel clinical model allows to systematically screen for promising (secondary) preventive therapy options. Moreover, future blood based neurochemical diagnostics of preclinical or early AD by means of multiplex assays seems to be promising. However, so far blood assays were not consistently validated by independent research groups and in contrast to CSF-NDD a blood-based diagnosis of AD is not yet available. PMID:25791051

  19. Cerebrospinal fluid biomarkers in trials for Alzheimer and Parkinson diseases.

    PubMed

    Lleó, Alberto; Cavedo, Enrica; Parnetti, Lucilla; Vanderstichele, Hugo; Herukka, Sanna Kaisa; Andreasen, Niels; Ghidoni, Roberta; Lewczuk, Piotr; Jeromin, Andreas; Winblad, Bengt; Tsolaki, Magda; Mroczko, Barbara; Visser, Pieter Jelle; Santana, Isabel; Svenningsson, Per; Blennow, Kaj; Aarsland, Dag; Molinuevo, José Luis; Zetterberg, Henrik; Mollenhauer, Brit

    2015-01-01

    Alzheimer disease (AD) and Parkinson disease (PD) are the most common neurodegenerative disorders. For both diseases, early intervention is thought to be essential to the success of disease-modifying treatments. Cerebrospinal fluid (CSF) can reflect some of the pathophysiological changes that occur in the brain, and the number of CSF biomarkers under investigation in neurodegenerative conditions has grown rapidly in the past 20 years. In AD, CSF biomarkers are increasingly being used in clinical practice, and have been incorporated into the majority of clinical trials to demonstrate target engagement, to enrich or stratify patient groups, and to find evidence of disease modification. In PD, CSF biomarkers have not yet reached the clinic, but are being studied in patients with parkinsonism, and are being used in clinical trials either to monitor progression or to demonstrate target engagement and downstream effects of drugs. CSF biomarkers might also serve as surrogate markers of clinical benefit after a specific therapeutic intervention, although additional data are required. It is anticipated that CSF biomarkers will have an important role in trials aimed at disease modification in the near future. In this Review, we provide an overview of CSF biomarkers in AD and PD, and discuss their role in clinical trials. PMID:25511894

  20. Two-compartment model of radioimmunotherapy delivered through cerebrospinal fluid

    PubMed Central

    He, Ping; Kramer, Kim; Smith-Jones, Peter; Zanzonico, Pat; Humm, John; Larson, Steven M.

    2011-01-01

    Purpose Radioimmunotherapy (RIT) using 131I-3F8 injected into cerebrospinal fluid (CSF) was a safe modality for the treatment of leptomeningeal metastases (JCO, 25:5465, 2007). A single-compartment pharmacokinetic model described previously (JNM 50:1324, 2009) showed good fitting to the CSF radioactivity data obtained from patients. We now describe a two-compartment model to account for the ventricular reservoir of 131I-3F8 and to identify limiting factors that may impact therapeutic ratio. Methods Each parameter was examined for its effects on (1) the area under the radioactivity concentration curve of the bound antibody (AUC[CIAR]), (2) that of the unbound antibody AUC[CIA], and (3) their therapeutic ratio (AUC [CIAR]/AUC[CIA]). Results Data fitting showed that CSF kBq/ml data fitted well using the two-compartment model (R=0.95±0.03). Correlations were substantially better when compared to the one-compartment model (R=0.92±0.11 versus 0.77±0.21, p=0.005). In addition, we made the following new predictions: (1) Increasing immunoreactivity of 131I-3F8 from 10% to 90% increased both (AUC[CIAR]) and therapeutic ratio ([AUC[CIAR]/AUC[CIA

  1. Increased cerebrospinal fluid fibrinogen in major depressive disorder

    PubMed Central

    Hattori, Kotaro; Ota, Miho; Sasayama, Daimei; Yoshida, Sumiko; Matsumura, Ryo; Miyakawa, Tomoko; Yokota, Yuuki; Yamaguchi, Shinobu; Noda, Takamasa; Teraishi, Toshiya; Hori, Hiroaki; Higuchi, Teruhiko; Kohsaka, Shinichi; Goto, Yu-ichi; Kunugi, Hiroshi

    2015-01-01

    Major depressive disorder (MDD) presumably includes heterogeneous subgroups with differing pathologies. To obtain a marker reflecting such a subgroup, we analyzed the cerebrospinal fluid (CSF) levels of fibrinogen, which has been reported to be elevated in the plasma of patients with MDD. Three fibrinogen-related proteins were measured using aptamer-based analyses and CSF samples of 30 patients with MDD and 30 controls. The numbers of patients with an excessively high level (>99 percentile of the controls) was significantly increased (17 to 23%). Measurement reproducibility of these results was confirmed by an ELISA for fibrinogen (Pearson’s r?=?0.77). In an independent sample set from 36 patients and 30 controls, using the ELISA, results were similar (22%). When these two sample sets were combined, the number of patients with a high fibrinogen level was significantly increased (15/66; odds ratio 8.53; 95% confidence interval 1.9–39.1, p?=?0.0011). By using diffusion tensor imaging, we found white matter tracts abnormalities in patients with a high fibrinogen level but not those patients with a normal fibrinogen level, compared with controls. Plasma fibrinogen levels were similar among the diagnostic groups. Our results point to a subgroup of MDD represented by increased CSF fibrinogen and white matter tract abnormalities. PMID:26081315

  2. Dynamic oxygen-enhanced MRI of cerebrospinal fluid.

    PubMed

    Mehemed, Taha M; Fushimi, Yasutaka; Okada, Tomohisa; Yamamoto, Akira; Kanagaki, Mitsunori; Kido, Aki; Fujimoto, Koji; Sakashita, Naotaka; Togashi, Kaori

    2014-01-01

    Oxygen causes an increase in the longitudinal relaxation rate of tissues through its T1-shortening effect owing to its paramagnetic properties. Due to such effects, MRI has been used to study oxygen-related signal intensity changes in various body parts including cerebrospinal fluid (CSF) space. Oxygen enhancement of CSF has been mainly studied using MRI sequences with relatively longer time resolution such as FLAIR, and T1 value calculation. In this study, fifteen healthy volunteers were scanned using fast advanced spin echo MRI sequence with and without inversion recovery pulse in order to dynamically track oxygen enhancement of CSF. We also focused on the differences of oxygen enhancement at sulcal and ventricular CSF. Our results revealed that CSF signal after administration of oxygen shows rapid signal increase in both sulcal CSF and ventricular CSF on both sequences, with statistically significant predominant increase in sulcal CSF compared with ventricular CSF. CSF is traditionally thought to mainly form from the choroid plexus in the ventricles and is absorbed at the arachnoid villi, however, it is also believed that cerebral arterioles contribute to the production and absorption of CSF, and controversy remains in terms of the precise mechanism. Our results demonstrated rapid oxygen enhancement in sulcal CSF, which may suggest inhaled oxygen may diffuse into sulcal CSF space rapidly probably due to the abundance of pial arterioles on the brain sulci. PMID:24956198

  3. Reduced cerebrospinal fluid ethanolamine concentration in major depressive disorder

    PubMed Central

    Ogawa, Shintaro; Hattori, Kotaro; Sasayama, Daimei; Yokota, Yuki; Matsumura, Ryo; Matsuo, Junko; Ota, Miho; Hori, Hiroaki; Teraishi, Toshiya; Yoshida, Sumiko; Noda, Takamasa; Ohashi, Yoshiaki; Sato, Hajime; Higuchi, Teruhiko; Motohashi, Nobutaka; Kunugi, Hiroshi

    2015-01-01

    Amino acids play key roles in the function of the central nervous system, and their alterations are implicated in psychiatric disorders. In the search for a biomarker for major depressive disorder (MDD), we used high-performance liquid chromatography to measure amino acids and related molecules in the cerebrospinal fluid (CSF) of 52 patients with MDD (42 depressed and 10 remitted; DSM-IV) and 54 matched controls. Significant differences were found in four amino acid concentrations between the depressed patients and controls. After Bonferroni correction, only ethanolamine (EA) levels remained significantly reduced in depressed patients (nominal P = 0.0000011). A substantial proportion of the depressed patients (40.5%) showed abnormally low CSF EA levels (<12.1??M) (P = 0.000033; OR = 11.6, 95% CI: 3.1–43.2). When patients with low EA and those with high EA levels were compared, the former had higher scores for overall depression severity (P = 0.0033) and ‘Somatic Anxiety’ symptoms (P = 0.00026). In unmedicated subjects, CSF EA levels showed a significant positive correlation with levels of homovanillic acid (P = 0.0030) and 5-hydroxyindoleacetic acid (P = 0.019). To our knowledge, this is the first study showing that patients with MDD have significantly lower CSF EA concentrations compared with control subjects. CSF EA could be a state-dependent biomarker for a subtype of MDD. PMID:25589364

  4. Clinical implications of acute cerebrospinal fluid changes following iophendylate myelography.

    PubMed

    Mehta, H J; Ramakantan, R; Piparia, D H; Hande, A M; Goel, A; Satoskar, A R; Dastur, F D

    1992-01-01

    Clinical features and serial cerebrospinal fluid (CSF) samples of 50 patients who underwent myelography with iophendylate were studied. Forty two patients (84%) developed one or more features suggestive of meningism lasting for 2-4 days. There was significant rise in the average (mean) CSF counts from 9.81 in the premyelogram sample to 532.6 at the end of 24 hours (p less than 0.001). Both neutrophil and lymphocyte (p less than 000) count increased. At the end of one week, there was significant decrease of total cells in the CSF to 204 (p less than 0.001). Both, neutrophils and lymphocytes decreased. There was significant rise in total proteins in the 24 hours sample, but the fall at one week was not significant statistically. The sugar and chloride values did not change significantly. All CSF samples were negative for bacterial cultures. In conclusion, a significant proportion of the patients undergoing iophendylate myelography develop clinical features suggestive of meningeal irritation and change in the CSF fractions suggestive of meningitis: however these changes are transient and do not warrant institution of chemotherapy or steroids. PMID:1512716

  5. [Cerebrospinal fluid in the diagnosis of spinal schistosomiasis].

    PubMed

    Tesser, Egídio; Reis, Maria de Lourdes Amud Ali dos; Borelli, Primavera; Matas, Sandro Luiz de Andrade; Reis Filho, João Baptista dos

    2005-09-01

    Cerebrospinal fluid (CSF) changes in spinal schistosomiasis have been described. Its characteristic features are mild to moderate pleocytosis, presence of eosinophils, slight to moderate protein increase, elevated gamma globulin concentration and a positive immune assay. Nevertheless, these abnormalities are not always present together and therefore difficulties may arise in the assessment of the diagnosis. The purpose of this paper is to evaluate the importance of each CSF alteration concerning the diagnosis in 22 cases of spinal schistosomiasis. According to the results, only 20% of the cases had all the five feature that are considered to be characteristic of spinal schistosomiasis. Abnormal cell count was present in 86%, protein increase in 77.3%, immunoglobulin G increase in 60,8%, eosinophils were present in 36.8% and indirect fluorescent antibody test was positive in 68.2%. In three cases all CSF parameters studied were within the normal limits. As the most specific test among those described was the indirect fluorescent antibody test, it should be regarded for the diagnosis. PMID:16172719

  6. Independent information from cerebrospinal fluid amyloid-? and florbetapir imaging in Alzheimer's disease.

    PubMed

    Mattsson, Niklas; Insel, Philip S; Donohue, Michael; Landau, Susan; Jagust, William J; Shaw, Leslie M; Trojanowski, John Q; Zetterberg, Henrik; Blennow, Kaj; Weiner, Michael W

    2015-03-01

    Reduced cerebrospinal fluid amyloid-?42 and increased retention of florbetapir positron emission tomography are biomarkers reflecting cortical amyloid load in Alzheimer's disease. However, these measurements do not always agree and may represent partly different aspects of the underlying Alzheimer's disease pathology. The goal of this study was therefore to test if cerebrospinal fluid and positron emission tomography amyloid-? biomarkers are independently related to other Alzheimer's disease markers, and to examine individuals who are discordantly classified by these two biomarker modalities. Cerebrospinal fluid and positron emission tomography amyloid-? were measured at baseline in 769 persons [161 healthy controls, 68 subjective memory complaints, 419 mild cognitive impairment and 121 Alzheimer's disease dementia, mean age 72 years (standard deviation 7 years), 47% females] and used to predict diagnosis, APOE ?4 carriage status, cerebral blood flow, cerebrospinal fluid total-tau and phosphorylated-tau levels (cross-sectionally); and hippocampal volume, fluorodeoxyglucose positron emission tomography results and Alzheimer's Disease Assessment Scale-cognitive subscale scores (longitudinally). Cerebrospinal fluid and positron emission tomography amyloid-? were highly correlated, but adjusting one of these predictors for the other revealed that they both provided partially independent information when predicting diagnosis, APOE ?4, hippocampal volume, metabolism, cognition, total-tau and phosphorylated-tau (the 95% confidence intervals of the adjusted effects did not include zero). Cerebrospinal fluid amyloid-? was more strongly related to APOE ?4 whereas positron emission tomography amyloid-? was more strongly related to tau levels (P < 0.05). Discordance (mainly isolated cerebrospinal fluid amyloid-? positivity) differed by diagnostic group (P < 0.001) and was seen in 21% of cognitively healthy people but only 6% in dementia patients. The finding that cerebrospinal fluid and positron emission tomography amyloid-? provide partially independent information about a wide range of Alzheimer's measures supports the theory that these modalities represent partly different aspects of Alzheimer's pathology. The fact that mismatch, with positive cerebrospinal fluid amyloid-? but normal positron emission tomography amyloid-?, is relatively common in cognitively healthy people may be considered when using these biomarkers to identify early stage Alzheimer's disease. Reduced cerebrospinal fluid amyloid-? may be more strongly related to early stage Alzheimer's disease, whereas increased positron emission tomography amyloid-? may be more strongly related to disease progression. PMID:25541191

  7. A new method for measuring cerebrospinal fluid flow in shunts.

    PubMed

    Hara, M; Kadowaki, C; Konishi, Y; Ogashiwa, M; Numoto, M; Takeuchi, K

    1983-04-01

    An implantable device for measurement of cerebrospinal fluid (CSF) flow in a ventriculoperitoneal shunt tube has been developed. The unit is energized by an extracorporeal high-frequency generator (200 KHz), and electrolysis creates bubbles in the shunt tube. Velocity of bubble flow is detected by a pair of ultrasonic Doppler probes placed a certain distance apart on the skin surface and in parallel with the implanted tube. The CSF flow rate is calculated taking into account velocity and tube diameter, and is expressed in ml/min. The unit consists of a coil with a capacitor, a silicon diode to rectify the high frequency, and a Zener diode to regulate maximum output voltage of 20 V. The output is fed to a pair of platinum electrodes placed inside the unit's tunnel through which the CSF flows. These components are molded in epoxy resin and coated with medical-grade silicone rubber. In animal experiments, CSF flow rates ranging from 0.033 to 1.0 ml/min could be measured by this flowmeter. Clinically, CSF flow has been measured to date in several cases. In two cases of communicating hydrocephalus occurring after the onset of cerebrovascular disease, and in which the CSF flow was continuously monitored for 24 hours, the flow rate ranged between 0.05 and 0.78 ml/min. The CSF flow rate fluctuates in a 24-hour period, increasing in the morning, especially between 12 midnight and 6 a.m., which suggests a circadian rhythm. PMID:6219190

  8. Endostatin level in cerebrospinal fluid of patients with Alzheimer's disease.

    PubMed

    Salza, Romain; Oudart, Jean-Baptiste; Ramont, Laurent; Maquart, François-Xavier; Bakchine, Serge; Thoannès, Henri; Ricard-Blum, Sylvie

    2015-01-01

    The aim of this study was to measure the level of endostatin, a fragment of collagen XVIII that accumulates in the brain of patients with Alzheimer's disease (AD), in the cerebrospinal fluids (CSF) of patients with neurodegenerative diseases. The concentrations of total protein, endostatin, amyloid-?1-42 peptide, tau, and hyperphosphorylated tau proteins were measured by enzyme-linked immunosorbent assay in CSF of patients with AD (n = 57), behavioral frontotemporal dementia (bvFTD, n = 22), non AD and non FTD dementia (nAD/nFTD, n = 84), and 45 subjects without neurodegenerative diseases. The statistical significance of the results was assessed by Mann-Whitney and Kruskal and Wallis tests, and by ROC analysis. The concentration of endostatin in CSF was higher than the levels of the three markers of AD both in control subjects and in patients with neurodegenerative diseases. The endostatin/amyloid-?1-42 ratio was significantly increased in patients with AD (257%, p < 0.0001) and nAD/nFTD (140%, p < 0.0001) compared to controls. The endostatin/tau protein ratio was significantly decreased in patients with AD (-49%, p < 0.0001) but was increased in bvFTD patients (89%, p < 0.0001) compared to controls. In the same way, the endostatin/hyperphosphorylated tau protein ratio was decreased in patients with AD (-21%, p = 0.0002) but increased in patients with bvFTD (81%, p = 0.0026), compared to controls. The measurement of endostatin in CSF and the calculation of its ratio relative to well-established AD markers improve the diagnosis of bvFTD patients and the discrimination of patients with AD from those with bvFTD and nAD/nFTD. PMID:25408220

  9. Cerebrospinal Fluid Biomarker Candidates Associated with Human WNV Neuroinvasive Disease

    PubMed Central

    Fraisier, Christophe; Papa, Anna; Granjeaud, Samuel; Hintzen, Rogier; Martina, Byron; Camoin, Luc; Almeras, Lionel

    2014-01-01

    During the last decade, the epidemiology of WNV in humans has changed in the southern regions of Europe, with high incidence of West Nile fever (WNF) cases, but also of West Nile neuroinvasive disease (WNND). The lack of human vaccine or specific treatment against WNV infection imparts a pressing need to characterize indicators associated with neurological involvement. By its intimacy with central nervous system (CNS) structures, modifications in the cerebrospinal fluid (CSF) composition could accurately reflect CNS pathological process. Until now, few studies investigated the association between imbalance of CSF elements and severity of WNV infection. The aim of the present study was to apply the iTRAQ technology in order to identify the CSF proteins whose abundances are modified in patients with WNND. Forty-seven proteins were found modified in the CSF of WNND patients as compared to control groups, and most of them are reported for the first time in the context of WNND. On the basis of their known biological functions, several of these proteins were associated with inflammatory response. Among them, Defensin-1 alpha (DEFA1), a protein reported with anti-viral effects, presented the highest increasing fold-change (FC>12). The augmentation of DEFA1 abundance in patients with WNND was confirmed at the CSF, but also in serum, compared to the control individual groups. Furthermore, the DEFA1 serum level was significantly elevated in WNND patients compared to subjects diagnosed for WNF. The present study provided the first insight into the potential CSF biomarkers associated with WNV neuroinvasion. Further investigation in larger cohorts with kinetic sampling could determine the usefulness of measuring DEFA1 as diagnostic or prognostic biomarker of detrimental WNND evolution. PMID:24695528

  10. Neonatal herpes simplex virus infections: HSV DNA in cerebrospinal fluid and serum

    PubMed Central

    Malm, G; Forsgren, M

    1999-01-01

    AIM—To investigate the diagnostic potential of herpes simplex virus (HSV) DNA in cerebrospinal fluid and serum; to correlate the findings with outcome in the child and with type of maternal infection.?METHODS—Cerebrospinal fluid and serum specimens from 36 children with verified neonatal HSV infections, diagnosed between 1973 and 1996, were examined using the polymerase chain reaction technique (PCR).?RESULTS—In 21 children for whom both cerebrospinal fluid and sera were available, HSV DNA was found in one or both specimens in 19(90%). Overall, HSV DNA was found in the cerebrospinal fluid of 74% of 27 children, and in the sera of 20 out of 30 children (67%). In two children HSV DNA was not demonstrable in either serum or cerebrospinal fluid. In sequential specimens from four children, the persistence of HSV DNA after the end of intravenous treatment was associated with a poor prognosis.?CONCLUSIONS—These findings indicate that HSV DNA detection in CSF and serum is highly sensitive for the diagnosis of neonatal HSV infections but does not replace the detection of virus in other locations using virus isolation and antigen detection.?? PMID:10375358

  11. Agents of equine viral encephalomyelitis: correlation of serum and cerebrospinal fluid antibodies.

    PubMed

    Keane, D P; Little, P B; Wilkie, B N; Artsob, H; Thorsen, J

    1988-04-01

    A survey was conducted by testing 115 paired equine serum and cerebrospinal fluid samples by hemagglutination-inhibition for antibodies to Powassan and snowshoe hare viruses, and by virus neutralization for antibodies to equine herpesvirus type 1. Twenty-five samples were from horses with spontaneous neurological disease and the remainder from horses euthanized because of various nonneurological disorders. All sera and cerebrospinal fluids were negative for antibodies to Powassan virus. Fifty-one sera (44.3%) and 15 cerebrospinal fluids (13.0%) had antibodies to snowshoe hare virus. Ninety-eight sera (85.2%) and four cerebrospinal fluids (3.5%) were positive for antibodies to equine herpesvirus type 1. Powassan virus was inoculated intracerebrally into one, and intravenously into four ponies. Neurological signs associated with a nonsuppurative encephalomyelitis occurred in three ponies. Antibodies to Powassan virus were detected in sera of all animals but in cerebrospinal fluids of only two. Powassan virus was isolated from brain and spinal cord of only the intracerebrally inoculated animal. PMID:2836046

  12. Effects of Proteins, Blood Cells and Glucose on the Viscosity of Cerebrospinal Fluid

    Microsoft Academic Search

    I. G. Bloomfield; I. H. Johnston; L. E. Bilston

    1998-01-01

    It has long been assumed that cerebrospinal fluid (CSF) is a newtonian fluid with viscosity similar to water, yet high protein content, has been postulated to increase the viscosity of CSF in vivo. Such an increase in viscosity may have serious implications for the effectiveness of surgical shunts implanted to re-establish the CSF flow in cases of abnormal CSF circulation.

  13. Mannan-binding lectin in cerebrospinal fluid: a leptomeningeal protein

    PubMed Central

    2012-01-01

    Background Mannan-binding lectin (MBL), a protein of the innate immune response is attracting increasing clinical interest, in particularly in relation to its deficiency. Due to its involvement in brain diseases, identifying the source of MBL in CSF is important. Analysis of cerebrospinal fluid (CSF) can provide data that discriminates between blood-, brain-, and leptomeninges-derived proteins. To detect the source of MBL in CSF we need to consider three variables: the molecular size-dependent concentration gradient between CSF and blood, the variation in transfer between blood and CSF, and the CSF MBL concentration correlation with the albumin CSF/serum quotient (QAlb), i.e., with CSF flow rate. Methods MBL was assayed in samples of CSF and serum with an ELISA, coated with anti MBL antibodies. Routine parameters such as albumin-, immunoglobulin- CSF/serum quotients, oligoclonal IgG and cell count were used to characterize the patient groups. Groups comprised firstly, control patients without organic brain disease with normal CSF and normal barrier function and secondly, patients without inflammatory diseases but with increased QAlb, i.e. with a blood CSF barrier dysfunction. Results MBL concentration in CSF was at least five-fold higher than expected for a molecular-size-dependent passage from blood. Secondly, in a QIgM/QAlb quotient diagram (Reibergram) 9/13 cases showed an intrathecal fraction in some cases over 80% of total CSF MBL concentration 3) The smaller inter-individual variation of MBL concentrations in CSF of the control group (CV?=?66%) compared to the MBL concentrations in serum (CV?=?146%) indicate an independent source of MBL in CSF. 4) The absolute MBL concentration in CSF increases with increasing QAlb. Among brain-derived proteins in CSF only the leptomeningeal proteins showed a (linear) increase with decreasing CSF flow rate, neuronal and glial proteins are invariant to changes of QAlb. Conclusions MBL in CSF is predominantly brain-derived and all results pointed to the leptomeningeal cells as the source of the protein. The evaluation of this protein requires the interpretation of its absolute concentrations in CSF as a function of the albumin quotient, QAlb. This recognition of MBL in brain cells opens a new field of discussion about the function of the innate immune response in CNS in cases of acute and chronic neurological diseases. PMID:22889364

  14. Cerebrospinal Fluid Steroidomics: Are Bioactive Bile Acids Present in Brain?*

    PubMed Central

    Ogundare, Michael; Theofilopoulos, Spyridon; Lockhart, Andrew; Hall, Leslie J.; Arenas, Ernest; Sjövall, Jan; Brenton, A. Gareth; Wang, Yuqin; Griffiths, William J.

    2010-01-01

    In this study we have profiled the free sterol content of cerebrospinal fluid by a combination of charge tagging and liquid chromatography-tandem mass spectrometry. Surprisingly, the most abundant cholesterol metabolites were found to be C27 and C24 intermediates of the bile acid biosynthetic pathways with structures corresponding to 7?-hydroxy-3-oxocholest-4-en-26-oic acid (7.170 ± 2.826 ng/ml, mean ± S.D., six subjects), 3?-hydroxycholest-5-en-26-oic acid (0.416 ± 0.193 ng/ml), 7?,x-dihydroxy-3-oxocholest-4-en-26-oic acid (1.330 ± 0.543 ng/ml), and 7?-hydroxy-3-oxochol-4-en-24-oic acid (0.172 ± 0.085 ng/ml), and the C26 sterol 7?-hydroxy-26-norcholest-4-ene-3,x-dione (0.204 ± 0.083 ng/ml), where x is an oxygen atom either on the CD rings or more likely on the C-17 side chain. The ability of intermediates of the bile acid biosynthetic pathways to activate the liver X receptors (LXRs) and the farnesoid X receptor was also evaluated. The acidic cholesterol metabolites 3?-hydroxycholest-5-en-26-oic acid and 3?,7?-dihydroxycholest-5-en-26-oic acid were found to activate LXR in a luciferase assay, but the major metabolite identified in this study, i.e. 7?-hydroxy-3-oxocholest-4-en-26-oic acid, was not an LXR ligand. 7?-Hydroxy-3-oxocholest-4-en-26-oic acid is formed from 3?,7?-dihydroxycholest-5-en-26-oic acid in a reaction catalyzed by 3?-hydroxy-?5-C27-steroid dehydrogenase (HSD3B7), which may thus represent a deactivation pathway of LXR ligands in brain. Significantly, LXR activation has been found to reduce the symptoms of Alzheimer disease (Fan, J., Donkin, J., and Wellington C. (2009) Biofactors 35, 239–248); thus, cholesterol metabolites may play an important role in the etiology of Alzheimer disease. PMID:19996111

  15. Radioimmunoassay of human growth hormone: technique and application to plasma, cerebrospinal fluid, and pituitary extracts

    PubMed Central

    Thomas, Frances J.; Lloyd, H. M.; Thomas, M. J.

    1972-01-01

    A radioimmunoassay for human growth hormone using activated charcoal is described and its precision, accuracy, and sensitivity are defined. Results are presented for growth hormone measurements in plasma obtained during hypoglycaemia induced with insulin in patients of short stature and during glucose tolerance tests in patients with acromegaly. The method was used to measure growth hormone concentrations in cerebrospinal fluid and in extracts of pituitary tumours. No growth hormone was detected in the cerebrospinal fluid of patients without acromegaly. In patients with acromegaly, the concentration of growth hormone in cerebrospinal fluid was measurable and was considerably elevated in one patient with extrasellar extension of a pituitary tumour. Extracts of chromophobe pituitary tumours contained very small concentrations of growth hormone. In extracts of pituitary tumours removed from acromegalic patients, concentrations fell either below or within the normal range. PMID:5086220

  16. Serum and cerebrospinal fluid concentration of clobazam and N-desmethylclobazam.

    PubMed

    Laux, G; Koeppen, D

    1984-07-01

    Twelve adult neurological patients undergoing lumbar puncture for diagnostic purposes received acute or repeated doses of the 1,5-benzodiazepine clobazam 20-40 mg/day. In one patient, additional ventricle cerebrospinal fluid samples were collected in the course of the diagnostic procedure and the respective concentrations of clobazam and N-desmethylclobazam were determined. The serum and lumbar cerebrospinal fluid concentrations of clobazam and its main metabolite N-desmethylclobazam were compared. The concentrations of both clobazam and N-desmethylclobazam were higher in serum than in cerebrospinal fluid (CSF). Clobazam and N-desmethylclobazam showed similar increase and decline in the ventricle CSF of one patient. This result differed from the pharmacokinetics of clobazam and its main metabolite in the blood which is characterized by a slower increase and a more prolonged elimination of N-desmethylclobazam, as opposed to the parent compound. PMID:6147313

  17. Nephelometric determination of total protein in cerebrospinal fluid and urine using benzalkonium chloride as precipitation reagent.

    PubMed

    Shephard, M D; Whiting, M J

    1992-07-01

    Four different protein precipitants, namely trichloroacetic acid, sulphosalicylic acid, benzethonium chloride and benzalkonium chloride, were used to estimate the total protein concentration in cerebrospinal fluid and urine by nephelometry. Protein determinations for 50 cerebrospinal fluid samples and 100 urine samples were compared with values obtained by a trichloroacetic acid-Ponceau S spectrophotometric method. All methods were correlated well, but total protein results using acid precipitants were usually lower, while results obtained using benzethonium chloride were generally higher, than results obtained by the trichloroacetic acid-Ponceau S method. Anomalous results were obtained for some urine samples with benzethonium chloride, but not with benzalkonium chloride. Assays using benzalkonium chloride as precipitating reagent showed good precision and closest agreement with the trichloroacetic acid-Ponceau S dye-binding method. The use of benzalkonium chloride as precipitant is recommended for automated cerebrospinal fluid and urine protein estimations by nephelometry. PMID:1642447

  18. Fluid perfusion as a method of cerebrospinal fluid formation rate--critical appraisal.

    PubMed

    Oreskovi?, Darko; Marakovi?, Jurica; Vuki?, Miroslav; Rados, Milan; Klarica, Marijan

    2008-01-01

    The aim of the study was to evaluate whether or not cerebrospinal fluid formation rate (Vf) calculated according to the equation of Heisey et al., truly show the produced cerebrospinal fluid. For this reason Vf was simulated (40.6 microL/min) by an infusion pump in a plastic cylinder and the evaluation was done by comparing the results obtained between the calculated Vf and the simulated one. In both cases the result should be the same (40.6 micro/min). Other types of experiments were carried out by ventriculocisternal perfusion (92.4 microL/min) on anaesthetized and sacrificed cats. If the equation is correct, the calculated Vf for sacrificed animals should be zero, because there is no Vf in dead animals. The fact that the calculated Vf (46.5 microL/min) in the plastic cylinder was different (p < 0.0001) from the simulated one (40.6 microL/min) and that Vf was calculated even for dead animals (3-5 microL/min) clearly shows the that perfusion method may not be an accurate method for determination of Vf. PMID:18405072

  19. Incidence of Cerebrospinal Fluid Leak after Microsurgical Removal of Vestibular Schwannomas

    Microsoft Academic Search

    A. Bani; J. M. Gilsbach

    2002-01-01

    Summary.  \\u000a ?Objectives: Cerebrospinal fluid (CSF) leak still remains an unresolved problem after microsurgical removal of vestibular schwannomas\\u000a (VS).\\u000a \\u000a \\u000a \\u000a ?Methods: 14 (6%) Cases of cerebrospinal fluid rhinorrhea and 3 cases with subcutaneous retro-auricular CSF collection, occurring in\\u000a a series of 224 patients operated on by the senior author (JMG) on VS between 1989–2000 via the suboccipital retrosigmoidal\\u000a approach were studied retrospectively.

  20. Capillary tube isotachophoresis of proteins in early postmortem serum, cerebrospinal fluid and pericardial fluid.

    PubMed

    Takahama, K; Seo, Y; Tomono, S; Yukawa, N

    1989-06-01

    Serum, cerebrospinal fluid (CSF) and pericardial fluid (PDF) obtained from 22 early cadavers were subjected to capillary tube isotachophoresis. Separated proteins were grouped into three main fractions, namely, Fr. 1, Fr. 2 and Fr. 3, in order of their decreasing effective (net) mobilities. The percentages of main fractions to total content were calculated by UV absorbance integration. It was found that Fr. 1 decreased and Fr. 2 increased in all three kinds of specimens with an increase in time following death. In serum and also in CSF, the degree of these changes between 6 and 58 hours following death seemed large enough (about 30%) to be used for crude estimations of early postmortem intervals. Changes in PDF proceeded more gradually than in serum and or in CSF, with only 5-20% changes during this period. PMID:2810897

  1. Age-Dependent Decline in the Apolipoprotein E Level in Cerebrospinal Fluid from Control Subjects and Its Increase in Cerebrospinal Fluid from Patients with Alzheimer’s Disease

    Microsoft Academic Search

    Ryuichi Fukuyama; Toshiki Mizuno; Satoru Mori; Katsuhiko Yanagisawa; Kenji Nakajima; Shinji Fushiki

    2000-01-01

    In order to address the significance of apolipoprotein E (apoE) in the pathogenesis as well as the clinical diagnosis of Alzheimer’s disease (AD), we measured its level in cerebrospinal fluid (CSF) from randomly selected Japanese control subjects at various ages (n = 36), which included 14 age-matched controls, and from AD patients including early-onset (n = 11, EOAD) and late-onset

  2. Whole-Genome Sequence of Multidrug-Resistant Staphylococcus caprae Strain 9557, Isolated from Cerebrospinal Fluid

    PubMed Central

    Zheng, Beiwen; Jiang, Xiawei; Li, Ang; Yao, Jian; Zhang, Jing; Hu, Xinjun

    2015-01-01

    Staphylococcus caprae strain 9557 was isolated from a cerebrospinal fluid sample. The assembled genome contained 2,747,651-bp nucleotides with 33.34% GC content. Consistent with its phenotypic characteristics, the genome harbors a varying repertoire of putative virulence factors involved in invasion, survival, and growth in the host cells. PMID:26139720

  3. Posttraumatic lumbar cerebrospinal fluid leak: detection by retrograde In111DTPA myeloscintography

    Microsoft Academic Search

    PATRICK M. COLLETTI; MICHAEL E. SIEGEL

    1981-01-01

    A case of lumbar cerebrospinal fluid (CSF) extravasation with an unsuspected traumatic meningocele after a gunshot wound was detected by means of retrograde myeloscintography using isobaric In-111-DTPA. Our experience and a review of the literature have provided evidence retrograde myeloscintography may be useful for detecting and delineating significant traumatic thoracic and lumbar CSF leaks.

  4. Seizures and retrograde amnesia with cerebrospinal fluid changes following H1N1 influenza vaccination

    Microsoft Academic Search

    Shivanthan Mitrakrishnan; Gamage Ranjanie; Thivakaran Thirunavakarasu; Caldera Manjula; Karunasena Nayananjani

    2011-01-01

    Vaccination against H1N1 influenza of healthcare workers of has been a standard measure to control the epidemic in many countries. Most side effects are minor and transient. Guillain Barre Syndrome and optic neuritis have been major concerns. We report a case of seizures with retrograde amnesia associated with cerebrospinal fluid changes following the H1N1 vaccine.

  5. Kappa Free Light Chains in Cerebrospinal Fluid as Markers of Intrathecal Immunoglobulin Synthesis

    Microsoft Academic Search

    Christian Fischer; Borros Arneth; Jurgen Koehler; Johannes Lotz; Karl J. Lackner

    Background: Intrathecal immunoglobulin synthesis is observed in several inflammatory disorders of the cen- tral nervous system, but its detection by current labora- tory tests is either tedious or relatively insensitive. We assessed the diagnostic accuracy of an assay for free light chains (FLC) in cerebrospinal fluid (CSF) and serum, and compared it with traditional tests for intra- thecal immunoglobulin synthesis.

  6. Evaluation of polyamine levels in cerebrospinal fluid of children with brain tumors

    Microsoft Academic Search

    Yoichi Takaue; Kenji Nishioka; Jan van Eys

    1986-01-01

    Cerebrospinal fluid (CSF) polyamine levels were analyzed retrospectively in 21 pediatric patients with different types of intracranial malignant tumors to determine the benefit of following these markers during the clinical management of brain tumors. The tumors included 16 medulloblastomas and 1 each of germinoma, ependymoma, primitive neuroectodermal tumor, astrocytoma, and malignant teratoma. The clinical course of each patient was followed

  7. On the origin of homovanillic acid (HVA) in the cerebrospinal fluid

    Microsoft Academic Search

    T. L. Sourkes

    1973-01-01

    Summary The contribution of homovanillic acid by the caudate nuclei to the cerebrospinal fluid has been assessed quantitatively on the basis of available clinical-neurochemical and animal-experimental data. A considerable fraction of the caudatal tissue may be involved in this function.

  8. Retroviral RNA identified in the cerebrospinal fluids and brains of individuals with schizophrenia

    Microsoft Academic Search

    Håkan Karlsson; Silke Bachmann; Johannes Schroder; Justin McArthur; E. Fuller Torrey; Robert H. Yolken

    2001-01-01

    Schizophrenia is a serious brain disease of uncertain etiology. A role for retroviruses in the etiopathogenesis of some cases of schizophrenia has been postulated on the basis of clinical and epidemiological observations. We found sequences homologous to retroviral pol genes in the cell-free cerebrospinal fluids (CSFs) of 10 of 35 (29%) individuals with recent-onset schizophrenia or schizoaffective disorder. Retroviral sequences

  9. Cerebrospinal fluid leakage complicating skull base fractures: analysis of 81 cases

    Microsoft Academic Search

    Selcuk Yilmazlar; Erhan Arslan; Hasan Kocaeli; Seref Dogan; Kaya Aksoy; Ender Korfali; Muammer Doygun

    2006-01-01

    The aim of this study was to evaluate the results of conservative and surgical management options for traumatic cerebrospinal fluid (CSF) leakage complicating skull base fractures. The subjects were 81 patients who were treated between 1996 and 2003 for CSF leaks that had persisted for 24 h or longer after head injury. For each case the medical records were reviewed, and

  10. Automated counting of cells in cerebrospinal fluid using the CellDyn-4000 haematology analyser.

    PubMed

    Hoffmann, Johannes J M L; Janssen, Willy C M

    2002-11-01

    Counting of cells in cerebrospinal fluid is currently performed manually. Because of the inherent analytical and economical disadvantages, we attempted to introduce a fully automated method. Therefore, we validated the Abbott CellDyn-4000 haematology analyser for counting cells in cerebrospinal fluid. The analyser was used in its standard configuration with the simple precaution of a preceding blank sample. As for leukocyte counting the analyser yielded high precision (CV approximately 5% above the upper reference limit), good linearity, low limit of detection (2/microl) and excellent correlation (r > 0.99) with the counting chamber method. The differential leukocyte count was equally accurate and precise, even in the low concentration range. Performance of the erythrocyte count was impaired by its high limit of detection (6/nl) and it appeared satisfactory only for detecting blood admixture due to traumatic puncture. The specificity of the analyser is excellent, since it correctly classified non-viable leukocytes and excluded yeast cells from the leukocyte count in a patient with cryptococcal meningitis. We conclude that the CellDyn-4000 is well suited for quickly and reliably counting leukocytes in cerebrospinal fluid. Developing some software modifications might make the analyser useful also for performing erythrocyte counting in cerebrospinal fluid. PMID:12521237

  11. Effect of cell phone magnetic fields on adjustable cerebrospinal fluid shunt valves

    Microsoft Academic Search

    Sadahiro Nomura; Hirosuke Fujisawa; Michiyasu Suzuki

    2005-01-01

    The rapid increase in the number of cell phone users has led to the suggestion that electromagnetic waves might affect medical devices. Cerebrospinal fluid shunt valves contain a magnetic device to allow the intracranial pressure setting to be adjusted transcutaneously. Among the valves tested, the settings of the Strata valve, the Hakim valve, and the Sophy valve were affected by

  12. Baseline Neuropsychological Profile and Cognitive Response to Cerebrospinal Fluid Shunting for Idiopathic Normal Pressure Hydrocephalus

    Microsoft Academic Search

    George Thomas; Matthew J. McGirt; Graeme Woodworth; Jennifer Heidler; Daniele Rigamonti; Argye E. Hillis; Michael A. Williams

    2005-01-01

    Objective: To evaluate neurocognitive changes and predict neurocognitive outcome after ventriculoperitoneal shunting for idiopathic normal pressure hydrocephalus (INPH). Background: Reports of neurocognitive response to shunting have been variable and studies that predict cognitive outcomes after shunting are limited. We reviewed our experience with cognitive outcomes for INPH patients who were selected for shunting based on abnormal cerebrospinal fluid (CSF) pressure

  13. Variables that influence HIV1 cerebrospinal fluid viral load in cryptococcal meningitis: a linear regression analysis

    Microsoft Academic Search

    Diego M Cecchini; Ana M Cañizal; Haroldo Rojas; Alicia Arechavala; Ricardo Negroni; María B Bouzas; Jorge A Benetucci

    2009-01-01

    BACKGROUND: The central nervous system is considered a sanctuary site for HIV-1 replication. Variables associated with HIV cerebrospinal fluid (CSF) viral load in the context of opportunistic CNS infections are poorly understood. Our objective was to evaluate the relation between: (1) CSF HIV-1 viral load and CSF cytological and biochemical characteristics (leukocyte count, protein concentration, cryptococcal antigen titer); (2) CSF

  14. The formation of cerebrospinal fluid: Nearly a hundred years of interpretations and misinterpretations

    Microsoft Academic Search

    D. Oreškovi?; M. Klarica

    2010-01-01

    The first scientific and experimental approaches to the study of cerebrospinal fluid (CSF) formation began almost a hundred years ago. Despite researchers being interested for so long, some aspects of CSF formation are still insufficiently understood. Today it is generally believed that CSF formation is an active energy consuming metabolic process which occurs mainly in brain ventricles, in choroid plexuses.

  15. Development of hydrocephalus and classical hypothesis of cerebrospinal fluid hydrodynamics: Facts and illusions

    Microsoft Academic Search

    D. Oreškovi?; M. Klarica

    2011-01-01

    According to the classical hypothesis of the cerebrospinal fluid (CSF) hydrodynamics, CSF is produced inside the brain ventricles, than it circulates like a slow river toward the cortical subarachnoid space, and finally it is absorbed into the venous sinuses. Some pathological conditions, primarily hydrocephalus, have also been interpreted based on this hypothesis. The development of hydrocephalus is explained as an

  16. Elevation of Cerebrospinal Fluid Protein in Patients with Diabetes Mellitus Is Associated with Duration of Diabetes

    Microsoft Academic Search

    Hiroshi Kobessho; Kenichi Oishi; Hirotoshi Hamaguchi; Fumio Kanda

    2008-01-01

    We investigated the relationships between total cerebrospinal fluid (CSF) protein in diabetic patients and the clinical characteristics of diabetes mellitus. The subjects comprised 16 diabetic patients (median age = 60.5 years, range = 47–71) who were studied retrospectively. Patients with diseases known to be associated with increases in total CSF protein were excluded as far as possible. The median total

  17. Comparative Evaluation of Colorimetric Microtiter Plate Systems for Detection of Herpes Simplex Virus in Cerebrospinal Fluid

    Microsoft Academic Search

    YI-WEI TANG; PAUL N. RYS; BARBARA J. RUTLEDGE; P. SHAWN MITCHELL; THOMAS F. SMITH; DAVID H. PERSING

    1998-01-01

    In the past few years, application of the PCR to the detection of herpes simplex virus (HSV) DNA in the cerebrospinal fluid (CSF) from patients with encephalitis and meningitis has become standard laboratory practice. However, from an operational perspective, the true diagnostic value of PCR in this setting is yet to be realized because most laboratories subject the amplification products

  18. Identification and characterization of immune complexes in the cerebrospinal fluid of patients with spinal cord schistosomiasis

    Microsoft Academic Search

    Teresa C. A. Ferrari; Luciana C. Faria; Tatiane S. Vilaça; Cristiane R. Correa; Alfredo M. Góes

    2011-01-01

    The pathogenesis of neuroschistosomiasis is largely unknown. Available evidence suggests that it depends on the presence of parasite eggs in the nervous tissue and on the host's immune response. We investigated the presence of immune complexes (ICs) in the cerebrospinal fluid (CSF) of four patients with spinal cord schistosomiasis (SCS), and performed their characterization. ICs containing soluble egg antigen of

  19. Cerebrospinal fluid B cells from multiple sclerosis patients are subject to normal germinal center selection

    Microsoft Academic Search

    Christopher Harp; Jane Lee; Doris Lambracht-Washington; Elizabeth Cameron; Gregory Olsen; Elliot Frohman; Michael Racke; Nancy Monson

    2007-01-01

    Previous findings from our laboratory demonstrated that some clonally expanded cerebrospinal fluid (CSF) B cells from MS patients exhibit diminished mutation targeting patterns in comparison to typical B cells selected in the context of germinal centers (GCs). In order to determine whether the overall CSF B cell repertoires adhered to mutation patterns typical of GC-selected B cells, we analyzed the

  20. Recommended Standard of Cerebrospinal Fluid Analysis in the Diagnosis of Multiple Sclerosis

    Microsoft Academic Search

    Mark S. Freedman; Edward J. Thompson; Florian Deisenhammer; Gavin Giovannoni; Guy Grimsley; Geoffrey Keir; Sten Öhman; Michael K. Racke; Mohammad Sharief; Christian J. M. Sindic; Finn Sellebjerg; Wallace W. Tourtellotte

    2005-01-01

    ew criteria for the diagnosis of multiple sclerosis (MS) were published as the result of an internationally formed committee. To increase the specificity of diagnosis and to minimize the number of false diagnoses, the committee recommended the use of both clinical and paraclinical criteria, the latter involving information obtained from magnetic resonance imaging, evoked potentials, and cerebrospinal fluid (CSF) analysis.

  1. Letter to the editor: Identification of Sarcocystis capracanis in cerebrospinal fluid from sheep with neurological disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A recent report (Formisano et al., 2013) identified clinical sacrocystosis in 2 adult sheep. The diagnosis relied primarily on characterization of DNA extracted from cerebrospinal fluid (CSF) and paraffin-embedded heart tissue. Parasites identified as merozoites were identified in CSF smears stained...

  2. Cerebrospinal Fluid Tyrosine and 3,4-Dihydroxyphenylacetic Acid Levels in Migraine Patients

    Microsoft Academic Search

    J Castillo; F Martínez; C Suárez; J Naveiro; M Lema; M Noya

    1996-01-01

    We studied biochemical parameters related with central dopaminergic neurotransmission in migraine patients during crisis. We determined tyrosine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in cerebrospinal fluid (CSF) of 47 patients, 29 suffering migraine without aura and 18 suffering migraine with aura, comparing them with 27 control subjects. Tyrosine levels did not differ significantly between patients and controls. The CSF concentration of

  3. Diagnostic value of cerebrospinal fluid antibodies in herpes simplex virus encephalitis

    Microsoft Academic Search

    M L Koskiniemi; A Vaheri

    1982-01-01

    Antibodies to different viruses and bacteria were measured in the cerebrospinal fluid (CSF) of six patients with herpes simplex virus encephalitis proven by brain biopsy and in five others with a presumptive diagnosis. Antibodies to herpes simplex virus but not to other organisms appeared in the CSF of all patients after the first weeks of the illness. Herpes simplex virus

  4. Cerebrospinal fluid leak associated with nasal continuous positive airway pressure treatment for obstructive sleep apnoea

    Microsoft Academic Search

    Jean Yared; Jaafar El Annan

    2010-01-01

    Clear rhinorrhoea is a common symptom in patients with obstructive sleep apnoea (OSA), which may worsen with nasal continuous positive airway pressure treatment (nCPAP). However, rhinorrhoea can also be the presenting symptom of cerebrospinal fluid (CSF) leak, which is due to a communication between the subarachnoid space and the nasal cavity or sinuses. We report another case of a patient

  5. [Assay of proteins in the urine and cerebrospinal fluid. Choice of a method in centrifugal analysis].

    PubMed

    Fontaine, M; Martin-Ponthieu, A; Richard, M J; Delescaut, M P; Baluch, L; Porchet, N

    1987-01-01

    The study consists in adapting two methods allowing estimation of proteins in cerebrospinal fluid and urine on a centrifugal analyzer using Coomassie Blue-SDS and benzethonium chloride. Results obtained with the two reagents are compared with turbidimetric technic using trichloroacetic acid, by statistic methods. PMID:3425986

  6. Cerebrospinal Fluid from Patients with Subarachnoid Haemorrhage and Vasospasm Enhances Endothelin Contraction in Rat Cerebral Arteries

    PubMed Central

    Assenzio, Barbara; Martin, Erica L.; Stankevicius, Edgaras; Civiletti, Federica; Fontanella, Marco; Boccaletti, Riccardo; Berardino, Maurizio; Mazzeo, AnnaTeresa; Ducati, Alessandro; Simonsen, Ulf; Mascia, Luciana

    2015-01-01

    Introduction Previous studies have suggested that cerebrospinal fluid from patients with subarachnoid hemorrhage (SAH) leads to pronounced vasoconstriction in isolated arteries. We hypothesized that only cerebrospinal fluid from SAH patients with vasospasm would produce an enhanced contractile response to endothelin-1 in rat cerebral arteries, involving both endothelin ETA and ETB receptors. Methods Intact rat basilar arteries were incubated for 24 hours with cerebrospinal fluid from 1) SAH patients with vasospasm, 2) SAH patients without vasospasm, and 3) control patients. Arterial segments with and without endothelium were mounted in myographs and concentration-response curves for endothelin-1 were constructed in the absence and presence of selective and combined ETA and ETB receptor antagonists. Endothelin concentrations in culture medium and receptor expression were measured. Results Compared to the other groups, the following was observed in arteries exposed to cerebrospinal fluid from patients with vasospasm: 1) larger contractions at lower endothelin concentrations (p<0.05); 2) the increased endothelin contraction was absent in arteries without endothelium; 3) higher levels of endothelin secretion in the culture medium (p<0.05); 4) there was expression of ETA receptors and new expression of ETB receptors was apparent; 5) reduction in the enhanced response to endothelin after ETB blockade in the low range and after ETA blockade in the high range of endothelin concentrations; 6) after combined ETA and ETB blockade a complete inhibition of endothelin contraction was observed. Conclusions Our experimental findings showed that in intact rat basilar arteries exposed to cerebrospinal fluid from patients with vasospasm endothelin contraction was enhanced in an endothelium-dependent manner and was blocked by combined ETA and ETB receptor antagonism. Therefore we suggest that combined blockade of both receptors may play a role in counteracting vasospasm in patients with SAH. PMID:25629621

  7. Monoaminc and metabolite levels in the cerebrospinal fluid of hibernating and euthermic marmots.

    PubMed

    Reid; Kilduff; Romero; Florant; Dement; Heller

    1992-03-01

    Cerebrospinal fluid from yellow-bellied marmots, Marmota flaviventris, was analysed for monoamine and monoamine metabolite content during euthermia and deep hibernation. Dopamine (DA) levels were decreased, while DA metabolite levels, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were dramatically increased in hibernating marmots. Serotonin (5-HT) and 5-hydroxyindoleacetic acid (5HIAA) levels were also greatly enhanced during hibernation while norepinephrine (NE) levels were only moderately increased. These findings demonstrate that cerebrospinal monoamine levels are dynamically altered during hibernation, such that DA versus 5-HT and NE levels undergo opposite changes. Therefore, these data indicate that DA, 5-HT and NE neuronal systems are differentially altered during hibernation in mammals. PMID:10607025

  8. Multiplicity of cerebrospinal fluid functions: New challenges in health and disease

    Microsoft Academic Search

    Conrad E Johanson; John A Duncan III; Petra M Klinge; Thomas Brinker; Edward G Stopa; Gerald D Silverberg

    2008-01-01

    This review integrates eight aspects of cerebrospinal fluid (CSF) circulatory dynamics: formation rate, pressure, flow, volume, turnover rate, composition, recycling and reabsorption. Novel ways to modulate CSF formation emanate from recent analyses of choroid plexus transcription factors (E2F5), ion transporters (NaHCO3 cotransport), transport enzymes (isoforms of carbonic anhydrase), aquaporin 1 regulation, and plasticity of receptors for fluid-regulating neuropeptides. A greater

  9. Ultrasensitive measurement of huntingtin protein in cerebrospinal fluid demonstrates increase with Huntington disease stage and decrease following brain huntingtin suppression

    PubMed Central

    Southwell, Amber L.; Smith, Stephen E.P.; Davis, Tessa R.; Caron, Nicholas S.; Villanueva, Erika B.; Xie, Yuanyun; Collins, Jennifer A.; Li Ye, Min; Sturrock, Aaron; Leavitt, Blair R.; Schrum, Adam G.; Hayden, Michael R.

    2015-01-01

    Quantitation of huntingtin protein in the brain is needed, both as a marker of Huntington disease (HD) progression and for use in clinical gene silencing trials. Measurement of huntingtin in cerebrospinal fluid could be a biomarker of brain huntingtin, but traditional protein quantitation methods have failed to detect huntingtin in cerebrospinal fluid. Using micro-bead based immunoprecipitation and flow cytometry (IP-FCM), we have developed a highly sensitive mutant huntingtin detection assay. The sensitivity of huntingtin IP-FCM enables accurate detection of mutant huntingtin protein in the cerebrospinal fluid of HD patients and model mice, demonstrating that mutant huntingtin levels in cerebrospinal fluid reflect brain levels, increasing with disease stage and decreasing following brain huntingtin suppression. This technique has potential applications as a research tool and as a clinical biomarker. PMID:26174131

  10. Ultrasensitive measurement of huntingtin protein in cerebrospinal fluid demonstrates increase with Huntington disease stage and decrease following brain huntingtin suppression.

    PubMed

    Southwell, Amber L; Smith, Stephen E P; Davis, Tessa R; Caron, Nicholas S; Villanueva, Erika B; Xie, Yuanyun; Collins, Jennifer A; Li Ye, Min; Sturrock, Aaron; Leavitt, Blair R; Schrum, Adam G; Hayden, Michael R

    2015-01-01

    Quantitation of huntingtin protein in the brain is needed, both as a marker of Huntington disease (HD) progression and for use in clinical gene silencing trials. Measurement of huntingtin in cerebrospinal fluid could be a biomarker of brain huntingtin, but traditional protein quantitation methods have failed to detect huntingtin in cerebrospinal fluid. Using micro-bead based immunoprecipitation and flow cytometry (IP-FCM), we have developed a highly sensitive mutant huntingtin detection assay. The sensitivity of huntingtin IP-FCM enables accurate detection of mutant huntingtin protein in the cerebrospinal fluid of HD patients and model mice, demonstrating that mutant huntingtin levels in cerebrospinal fluid reflect brain levels, increasing with disease stage and decreasing following brain huntingtin suppression. This technique has potential applications as a research tool and as a clinical biomarker. PMID:26174131

  11. Soluble Megalin is Reduced in Cerebrospinal Fluid Samples of Alzheimer’s Disease Patients

    PubMed Central

    Spuch, Carlos; Antequera, Desireé; Pascual, Consuelo; Abilleira, Soledad; Blanco, María; Moreno-Carretero, María José; Romero-López, Jesús; Ishida, Tetsuya; Molina, Jose Antonio; Villarejo, Alberto; Bermejo-Pareja, Felix; Carro, Eva

    2015-01-01

    Megalin or low-density lipoprotein receptor-related protein-2 is a member of the low-density lipoprotein receptor family, which has been linked to Alzheimer’s disease (AD) by clearing brain amyloid ?-peptide (A?) across the blood–cerebrospinal fluid barrier at the choroid plexus. Here, we found a soluble form of megalin secreted from choroid plexus epithelial cells. Soluble megalin levels were also localized in the human cerebrospinal fluid (CSF), being reduced in AD patients. We have also shown that soluble megalin binding to A? is decreased in the CSF of AD patients, suggesting that decreased sequestration of A? in the CSF could be associated with defective clearance of A? and an increase of brain A? levels. Thus, therapies, which increase megalin expression, at the choroid plexus and/or enhance circulating soluble megalin hold potential to control brain A?-related pathologies in AD. PMID:25926771

  12. Increased Selenoprotein P in Choroid Plexus and Cerebrospinal Fluid in Alzheimer’s Disease Brain

    PubMed Central

    Rueli, Rachel H.L.H.; Parubrub, Arlene C.; Dewing, Andrea S.T.; Hashimoto, Ann C.; Bellinger, Miyoko T.; Weeber, Edwin J.; Uyehara-Lock, Jane H.; White, Lon R.; Berry, Marla J.; Bellinger, Frederick P.

    2015-01-01

    Subjects with Alzheimer’s disease (AD) have elevated brain levels of the selenium transporter selenoprotein P (Sepp1). We investigated if this elevation results from increased release of Sepp1 from the choroid plexus (CP). Sepp1 is significantly increased in CP from AD brains in comparison to non-AD brains. Sepp1 localizes to the trans-Golgi network within CP epithelia, where it is processed for secretion. The cerebrospinal fluid from AD subjects also contains increased levels Sepp1 in comparison to non-AD subjects. These findings suggest that AD pathology induces increased levels of Sepp1 within CP epithelia for release into the cerebrospinal fluid to ultimately increase brain selenium. PMID:25298198

  13. Assessment of the benzethonium chloride method for routine determination of protein in cerebrospinal fluid and urine.

    PubMed

    Flachaire, E; Damour, O; Bienvenu, J; Aouiti, T; Later, R

    1983-02-01

    We have tested the characteristics of the method of Iwata and Nishikaze (Clin Chem 25: 1317, 1979). The linearity, sensitivity, and precision are satisfactory and the reactivity of benzethonium chloride with various proteins (albumin, immunoglobulins) is the same. The method has been compared with Meulemans's technique (Clin Chim Acta 5: 757, 1960), routinely used in our laboratories, by analysis of 82 samples of cerebrospinal fluid (CSF) and 119 samples of urine. Our results for cerebrospinal fluid agree well with those of Iwata and Nishikaze (r = 0.976; y = 0.992x - 0.013), but we find their method unsuitable for urinary protein determination, probably because of interfering compounds in urine. PMID:6821941

  14. Age-related changes in choroid plexus and blood–cerebrospinal fluid barrier function in the sheep

    Microsoft Academic Search

    R. L. Chen; N. A. Kassem; Z. B. Redzic; C. P. C. Chen; M. B. Segal; J. E. Preston

    2009-01-01

    Dysfunction of the choroid plexuses (CPs) and the blood–cerebrospinal fluid barrier (BCSFB) might contribute to age-related cognitive decline and neurodegenerative disease. We used the CPs from young (1–2 years), middle-aged (3–6 years) and old (7–10 years) sheep to explore effects of aging on various aspects of CP and BCSFB functions. Total protein in the cerebrospinal fluid (CSF) was significantly higher

  15. Choroidal Proteins Involved in Cerebrospinal Fluid Production may be Potential Drug Targets for Alzheimer’s Disease Therapy

    PubMed Central

    Wostyn, Peter; Audenaert, Kurt; De Deyn, Peter Paul

    2011-01-01

    Alzheimer’s disease is known to be the most common form of dementia in the elderly. It is clinically characterized by impairment of cognitive functions, as well as changes in personality, behavioral disturbances and an impaired ability to perform activities of daily living. To date, there are no effective ways to cure or reverse the disease. Genetic studies of early-onset familial Alzheimer’s disease cases revealed causative mutations in the genes encoding ?-amyloid precursor protein and the ?-secretase-complex components presenilin-1 and presenilin-2, supporting an important role of ?-amyloid in the pathogenesis of Alzheimer’s disease. Compromised function of the choroid plexus and defective cerebrospinal fluid production and turnover, with diminished clearance of ?-amyloid, may play an important role in late-onset forms of Alzheimer’s disease. If reduced cerebrospinal fluid turnover is a risk factor for Alzheimer’s disease, then therapeutic strategies to improve cerebrospinal fluid flow are reasonable. However, the role of deficient cerebrospinal fluid dynamics in Alzheimer’s disease and the relevance of choroidal proteins as potential therapeutic targets to enhance cerebrospinal fluid turnover have received relatively little research attention. In this paper, we discuss several choroidal proteins, such as Na+-K+ ATPase, carbonic anhydrase, and aquaporin 1, that may be targets for pharmacological up-regulation of cerebrospinal fluid formation. The search for potentially beneficial drugs useful to ameliorate Alzheimer’s disease by facilitating cerebrospinal fluid production and turnover may be an important area for future research. However, the ultimate utility of such modulators in the management of Alzheimer’s disease remains to be determined. Here, we hypothesize that caffeine, the most commonly used psychoactive drug in the world, may be an attractive therapeutic candidate for treatment of Alzheimer’s disease since long-term caffeine consumption may augment cerebrospinal fluid production. Other potential mechanisms of cognitive protection by caffeine have been suggested by recent studies. PMID:21487536

  16. Access of HTB, main metabolite of triflusal, to cerebrospinal fluid in healthy volunteers

    Microsoft Academic Search

    M. Valle; M. J. Barbanoj; A. Donner; I. Izquierdo; U. Herranz; N. Klein; H. G. Eichler; M. Müller; M. Brunner

    2005-01-01

    Objective: Triflusal has been shown to exert neuroprotective effects by downregulating molecules considered responsible for the development of Alzhei- mer's disease (AD). The aim of this study was to develop a population pharmacokinetic model to characterize plasma and cerebrospinal fluid (CSF) pharmacokinetics of the main active metabolite of triflusal—HTB (2-hy- droxy-4-trifluoro-methylbenzoic acid)—in healthy vol- unteers. Methods: Data from two studies

  17. Cerebrospinal fluid biomarkers in parkinsonian conditions: an update and future directions

    PubMed Central

    Magdalinou, Nadia; Lees, Andrew J; Zetterberg, Henrik

    2014-01-01

    Parkinsonian diseases comprise a heterogeneous group of neurodegenerative disorders, which show significant clinical and pathological overlap. Accurate diagnosis still largely relies on clinical acumen; pathological diagnosis remains the gold standard. There is an urgent need for biomarkers to diagnose parkinsonian disorders, particularly in the early stages when diagnosis is most difficult. In this review, several of the most promising cerebrospinal fluid candidate markers will be discussed. Their strengths and limitations will be considered together with future developments in the field. PMID:24691581

  18. A mathematical study of human intracranial hydrodynamics part 1—The cerebrospinal fluid pulse pressure

    Microsoft Academic Search

    Mauro Ursino

    1988-01-01

    An original mathematical model of human intracranial hydrodynamics is proposed. Equations able to mimic the behavior of the\\u000a intracranial arterial vascular bed, intracranial venous vascular bed, cerebrospinal fluid absorption and production processes,\\u000a and the constancy of overall intracranial volume are separately presented and discussed. The model parameters were given normal\\u000a values computed using physiological considerations and recent anatomical data. In

  19. Blood and cerebrospinal fluid pharmacokinetics of the novel anticonvulsant levetiracetam (ucb L059) in the rat

    Microsoft Academic Search

    H. C Doheny; N Ratnaraj; M. A Whittington; J. G. R Jefferys; P. N Patsalos

    1999-01-01

    The temporal pharmacokinetic interrelationship of levetiracetam in blood and cerebrospinal fluid (CSF) was studied after acute intraperitoneal administration of levetiracetam (20, 40 and 80 mg\\/kg), using an animal model that permits concurrent blood and CSF sampling in freely moving rats. After administration, levetiracetam rapidly appeared in both serum (time to maximum concentration (Tmax) mean range 0.25–0.50 h) and CSF (Tmax

  20. The particles of the embryonic cerebrospinal fluid: How could they influence brain development?

    Microsoft Academic Search

    Isabelle Bachy; Renata Kozyraki; Marion Wassef

    2008-01-01

    During brain development, the embryonic cerebrospinal fluid (E-CSF) allows brain expansion and promotes neuroepithelial cell survival, proliferation or differentiation. Previous analyses of E-CSF content have revealed a high protein concentration and the presence of membranous particles. The role of these particles in the E-CSF remains poorly investigated. In this study we showed that the E-CSF contains at least two pools

  1. A new procedure for detecting brain-specific proteins in cerebrospinal fluid

    Microsoft Academic Search

    P. Davidsson; R. Ekman; K. Blennow

    1997-01-01

    Summary We have developed a new procedure, including three affinity chromatography steps, micro-reversed phase high pressure liquid chromatography (mR-HPLC) and Western blotting\\/mass spectrometric analysis to study central nervous system (CNS) specific proteins in human cerebrospinal fluid (CSF) in order to find biochemical markers for neuronal and synaptic function and pathology in degenerative brain disorders. After the three affinity chromatography steps,

  2. Cerebrospinal fluid biomarkers in parkinsonian conditions: an update and future directions.

    PubMed

    Magdalinou, Nadia; Lees, Andrew J; Zetterberg, Henrik

    2014-10-01

    Parkinsonian diseases comprise a heterogeneous group of neurodegenerative disorders, which show significant clinical and pathological overlap. Accurate diagnosis still largely relies on clinical acumen; pathological diagnosis remains the gold standard. There is an urgent need for biomarkers to diagnose parkinsonian disorders, particularly in the early stages when diagnosis is most difficult. In this review, several of the most promising cerebrospinal fluid candidate markers will be discussed. Their strengths and limitations will be considered together with future developments in the field. PMID:24691581

  3. Sequential analysis of biomarkers in cerebrospinal fluid and serum during invasive meningococcal disease

    Microsoft Academic Search

    O. Beran; D. A. Lawrence; N. Andersen; O. Dzupova; J. Kalmusova; M. Musilek; M. Holub

    2009-01-01

    The aim of the present study was to determine the profile of different inflammatory molecules in serum and cerebrospinal fluid\\u000a (CSF) during invasive meningococcal disease (IMD). Their relationship with IMD severity was also assessed. A cohort of 12\\u000a patients with IMD was investigated. Paired serum and CSF samples were obtained at the time of diagnostic and follow-up lumbar\\u000a puncture and

  4. Choroid Plexus and Aquaporin1: A Novel Explanation of Cerebrospinal Fluid Production

    Microsoft Academic Search

    P. L. Longatti; L. Basaldella; E. Orvieto; A. Fiorindi; A. Carteri

    2004-01-01

    Aquaporins are selective water channel proteins that play a central role in the homeostasis of human body water. The choroid plexus (CP) is considered to be the main cerebrospinal fluid (CSF)-producing structure. In this study, six specimens of normal human CP obtained during surgery were analyzed by immunohistochemistry techniques for aquaporin-1 (AQP1) expression and distribution. Intense, uniformly distributed AQP1 immunostaining

  5. Manganese, copper, and zinc in cerebrospinal fluid from patients with multiple sclerosis

    Microsoft Academic Search

    Torun M. Melø; Cecilie Larsen; Linda R. White; Jan Aasly; Torill E. Sjøbakk; Trond P. Flaten; Ursula Sonnewald; Tore Syversen

    2003-01-01

    The concentrations of manganese, copper, and zinc in cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS)\\u000a and patients with no known neurological disease (control group) were measured. Manganese and copper levels were determined\\u000a by two different analytical methods: atomic absorption spectrometry (AAS) and high-resolution inductively coupled plasma-mass\\u000a spectrometry (HR-ICP-MS), whereas zinc levels were determined by HR-ICP-MS only. Manganese levels

  6. Detection of cancer cells in the cerebrospinal fluid: current methods and future directions

    Microsoft Academic Search

    Cody L Weston; Michael J Glantz; James R Connor

    2011-01-01

    The spread of cancer into the central nervous system is a serious problem leading to neurological symptoms and rapid mortality.\\u000a The current tools available for detecting the spread of cancer into the cerebrospinal fluid (CSF) are cytology, neurologic\\u000a examination, and neuroimaging. All three of these methods can be applied in concert to reach a diagnosis, but they all suffer\\u000a from

  7. Erythropoietin in Cerebrospinal Fluid: Age-related Reference Values and Relevance in Neurological Disease

    Microsoft Academic Search

    Karin Widl; Johannes Brettschneider; Dagmar Schattauer; Sigurd Süßmuth; Roman Huber; Albert C. Ludolph; Hayrettin Tumani

    2007-01-01

    We aimed to establish age-related reference values for Erythropoietin (EPO) in cerebrospinal fluid (CSF) and to evaluate concentrations\\u000a in neurological diseases. CSF and serum EPO was measured in controls with tension-type headache (CTTH), in patients with ALS,\\u000a dementia and depression using ELISA technique.\\u000a \\u000a Stability experiments showed CSF EPO to be stable for two and a half months and over two

  8. Primary Spontaneous Cerebrospinal Fluid Leaks and Idiopathic Intracranial Hypertension

    PubMed Central

    Pérez, Mario A.; Bialer, Omer Y.; Bruce, Beau B.; Newman, Nancy J.; Biousse, Valérie

    2014-01-01

    Introduction Idiopathic intracranial hypertension (IIH) is increasingly recognized as a cause of spontaneous cerebrospinal (CSF) leak in the ENT and neurosurgical literature. The diagnosis of IIH in patients with spontaneous CSF leaks is classically made a few weeks after surgical repair of the CSF leak when symptoms and signs of elevated intracranial pressure (ICP) appear. Methods Case reports and literature review. Two young obese women developed spontaneous CSF rhinorrhea related to an empty sella in one, and a cribriform plate encephalocele in the other. Both patients underwent surgical repair of the CSF leak. A few weeks later, they developed chronic headaches and bilateral papilledema. Lumbar punctures showed elevated CSF-opening pressures with normal CSF contents, with temporary improvement of headaches. A man with a three-year history of untreated IIH developed spontaneous CSF rhinorrhea. He experienced improvement of his headaches and papilledema after a CSF shunting procedure, and the rhinorrhea resolved after endoscopic repair of the leak. Results These cases and the literature review confirm a definite association between IIH and spontaneous CSF leak based on: 1) similar demographics; 2) increased ICP in some patients with spontaneous CSF leak after leak repair; 3) higher rate of leak recurrence in patients with raised ICP; 4) patients with intracranial hypertension secondary to tumors may develop CSF leak, confirming that raised ICP from other causes than IIH can cause CSF leak. Conclusions CSF leak may occasionally keep IIH patients symptom-free; however, classic symptoms and signs of intracranial hypertension may develop after the CSF leak is repaired, exposing these patients to a high risk of recurrence of the leak unless an ICP-lowering intervention is performed. PMID:24042170

  9. Development and functions of the choroid plexus-cerebrospinal fluid system.

    PubMed

    Lun, Melody P; Monuki, Edwin S; Lehtinen, Maria K

    2015-08-01

    The choroid plexus (ChP) is the principal source of cerebrospinal fluid (CSF), which has accepted roles as a fluid cushion and a sink for nervous system waste in vertebrates. Various animal models have provided insights into how the ChP-CSF system develops and matures. In addition, recent studies have uncovered new, active roles for this dynamic system in the regulation of neural stem cells, critical periods and the overall health of the nervous system. Together, these findings have brought about a paradigm shift in our understanding of brain development and health, and have stimulated new initiatives for the treatment of neurological disease. PMID:26174708

  10. Case of pediatric optic pathway oligodendroglioma presenting widespread invasion and dissemination in the cerebrospinal fluid.

    PubMed

    Katayama, Kosuke; Asano, Kenichiro; Ohkuma, Hiroki; Terui, Kiminori; Sasaki, Shinya; Sato, Tomohiko; Ito, Etsuro; Komori, Takashi

    2014-07-01

    Optic pathway oligodendrogliomas are a rare form of pediatric intracranial tumor. A 10-year-old girl presented with symptoms of hydrocephalus and seizure. Head computed tomography and magnetic resonance images showed hydrocephalus, chiasmal tumor, and enlarged and tortuous optic nerves. The tumor was partially removed by operation and diagnosed as oligodendroglioma. Operatively, there was evidence of cerebrospinal fluid dissemination in the sylvian fissure indicating widespread invasion. After the operation, Packer's regimen (vincristine and carboplatin therapy) was administered. However, magnetic resonance images obtained 2 months after the operation revealed enlargement of the original tumor and the appearance of new lesions, and treatment was changed to irradiation and temozolomide therapy according to the presence of a high-grade glioma. Two years after the operation, the patient is free of neurological symptoms, and the tumor is controlled with partial response. This is the first report of pediatric optic pathway oligodendroglioma presenting widespread invasion and cerebrospinal dissemination. PMID:23996461

  11. Coupling poroelasticity and CFD for cerebrospinal fluid hydrodynamics.

    PubMed

    Tully, Brett; Ventikos, Yiannis

    2009-06-01

    This research uses a novel coupling of poroelastic theory and computational fluid dynamics to investigate acute hydrocephalus resulting from stenosis of the cerebral aqueduct. By coupling poroelastic theory with a multidimensional simulation of the cerebral aqueduct we are able to investigate, for the first time, the impact of physically relevant stenosis patterns on ventricular enlargement, accounting for the nonintuitive long time history responses of the ventricular system. Preliminary findings demonstrate clearly the importance that the fluidic-poroelastic coupling plays: ventricular enlargement is significantly smaller with local stenosis patterns and almost all of the observable pressure drop occurs across the stenosis. Short timescale effects [O(heartbeat)] are explored and their contribution to the long timescales interrogated. PMID:19304478

  12. Cytomegalovirus associated transverse myelitis in an immunocompetent host with DNA detection in cerebrospinal fluid; a case report

    PubMed Central

    2012-01-01

    Background Cytomegalovirus associated transverse myelitis among immunocompetent adults has been rarely reported. We report a patient presenting with clinical myelitis followed by previously unreported finding of cytomegalovirus deoxyribonucleic acid in cerebrospinal fluid. Case report A forty year old immunocompetent male presented with acute onset progressive bilateral lower limb weakness. His spinal magnetic resonance imaging findings, cerebrospinal fluid analysis and clinical picture were compatible with transverse myelitis. Polymerase chain reaction of the cerebrospinal fluid for cytomegalovirus was positive while other infectious agents were not detected by serology or polymerase chain reaction. He was treated with intravenous ganciclovir with partial clinical response. Conclusion Viral genome detection in the cerebrospinal fluid was performed but negative in five out of ten reported cases of cytomegalovirus associated transverse myelitis in the immunocompetent host. In previous cases the inability to isolate the virus in cerebrospinal fluid was considered favouring an immunological mechanism leading to pathogenesis rather than direct viral toxicity but this case is against that theory. This case highlights the fact that Cytomegalovirus should be considered as an aetiological agent in patients with transverse myelitis and that the virus may cause serious infections in immunocompetent host. Therefore this report is of importance to neurologists and physicians in general. PMID:22818393

  13. Prostaglandin D synthase isoforms from cerebrospinal fluid vary with brain pathology.

    PubMed

    Harrington, Michael G; Fonteh, Alfred N; Biringer, Roger G; R Hühmer, Andreas F; Cowan, Robert P

    2006-01-01

    Glutathione independent prostaglandin D synthase (Swissprot P41222, PTGDS) has been identified in human cerebrospinal fluid and some changes in PTGDS in relation to disease have been reported. However, little is known of the extent that PTGDS isoforms fluctuate across a large range of congenital and acquired diseases. The purpose of this study was to examine changes in PTGDS isoforms in such a population. Spinal fluid from 22 healthy study participants (normal controls) with no classifiable neurological or psychiatric diagnosis was obtained and PTGDS isoforms were identified by specific immunostaining and mass spectrometry after denaturing 2D gel electrophoresis. The PTGDS isoforms in controls consisted of five charge isoforms that were always present and a small number of occasional, low abundance isoforms. A qualitative survey of 98 different people with a wide range of congenital and acquired diseases revealed striking changes. Loss of the control isoforms occurred in congenital malformations of the nervous system. Gain of additional isoforms occurred in some degenerative, most demyelinating and vasculitic diseases, as well as in Creutzfeldt-Jakob disease. A retrospective analysis of published data that quantified relative amounts of PTGDS in multiple sclerosis, schizophrenia and Parkinson's disease compared to controls revealed significant dysregulation. It is concluded that qualitative and quantitative fluctuations of cerebrospinal fluid PTGDS isoforms reflect both major and subtle brain pathophysiology. PMID:16410653

  14. Cerebrospinal fluid and lumbar puncture: the story of a necessary procedure in the history of medicine.

    PubMed

    Zambito Marsala, Sandro; Gioulis, Manuela; Pistacchi, Michele

    2015-06-01

    The aim of our work was to investigate the different historical stages that led gradually to the discovery of the anatomical structures that form and contain cerebrospinal fluid (CSF), until the Quincke idea, to collect the liquid directly at the lumbar level delivering to humanity a diagnostic tool present and absolutely irreplaceable in everyday clinical practice. This is done through consultation of all the historical medical literature, together with the critical examination of the original articles when available in the most rigorous chronological and speculative order, which enabled knowledge advancement. PMID:25670660

  15. Cerebrospinal fluid rhinorrhea following surgery for acoustic neurinoma. Report of two cases.

    PubMed

    Gordon, D S; Kerr, A G

    1986-04-01

    In a series of 48 patients with acoustic neurinoma removed by the suboccipital route, one patient developed cerebrospinal fluid rhinorrhea and another patient had delayed-onset meningitis. Each complication was attributed to opening the posteromedial air-cell tract in the posterior wall of the internal auditory meatus. In operations requiring removal of the posterior meatal wall, it is important to look for the air-cell tract which may not be apparent on computerized tomography. If the tract is opened the cells should be occluded by bone wax. PMID:3950753

  16. Effect of radiation on the penetration of irinotecan in rat cerebrospinal fluid

    Microsoft Academic Search

    Amit Khatri; M. Waleed Gaber; Richard C. Brundage; Michael D. Naimark; Suzan K. Hanna; Clinton F. Stewart; Mark N. Kirstein

    Purpose  Anticancer agents are useful for treating brain tumors, but sub therapeutic concentrations due to decreased blood–brain barrier\\u000a (BBB) penetration limit their effectiveness. This study evaluated the effect of cranial radiation on the pharmacokinetics\\u000a of irinotecan in plasma and cerebrospinal fluid (CSF).\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Rats (n = 48) were treated with irinotecan (10 mg\\/kg), and then administered 10 or 20 Gy or sham irradiation as control after

  17. Digital subtraction cisternography: a new approach to fistula localisation in cerebrospinal fluid rhinorrhoea.

    PubMed Central

    Byrne, J V; Ingram, C E; MacVicar, D; Sullivan, F M; Uttley, D

    1990-01-01

    Positive contrast cisternography with digital subtraction of fluoroscopy images before computed tomography (CT) was employed in the investigation of eight patients with cerebrospinal fluid (CSF) rhinorrhoea. Fistulae were visualised by preliminary digital subtraction cisternography (DSC) in six patients and in five patients the sites of leakage were confirmed at surgery. Fluoroscopy facilitated interpretation of CT in all the positive studies and in two patients provided information which could not be deduced from CT cisternography (CTC) alone. The combined technique is recommended for the investigation of patients with recurrent and post operative CSF rhinorrhoea and when CTC alone fails to identify the site of leakage. Images PMID:2292701

  18. Endoscopic pedicled nasoseptal flap repair of spontaneous sphenoid sinus cerebrospinal fluid leaks.

    PubMed

    Gunaratne, Dakshika Abeydeera; Singh, Narinder Pal

    2015-01-01

    Spontaneous cerebrospinal fluid (CSF) leaks in the sphenoid sinus are an uncommon but potentially significant condition associated with thin pneumatised bone, obesity and raised intracranial pressure. Despite advances in endoscopic sinus surgery, successful repair remains problematic due to limitations in visualisation, access and management of underlying aetiological factors. Utilisation of vascularised tissue in the primary repair process of sphenoid CSF leaks is yet to be well explored in the literature. In this series, we describe our surgical approach and explore related clinical, pathological and operative factors in three cases of spontaneous sphenoid sinus CSF leaks, successfully repaired on first attempt with the use of a vascularised nasoseptal flap. PMID:25926586

  19. Endoscopic repair of cerebrospinal fluid rhinorrhea: is it the treatment of choice?

    PubMed

    Nachtigal, D; Frenkiel, S; Yoskovitch, A; Mohr, G

    1999-06-01

    Between 1991 and 1998, 12 patients with cerebrospinal fluid rhinorrhea were operated on using the intranasal endoscopic approach. The procedure was successful in 10 cases. The endoscopic approach failed in two patients who had larger bony defects and herniating meningoencephaloceles. This paper analyzes the case material with respect to the etiology and site of leakage. The value of computed tomography and magnetic resonance imaging for preoperative localization of the leak is discussed. The technique of underlay fascia graft is described and discussion ensues regarding potential pitfalls that may lead to failure of leak closure. PMID:10410342

  20. Lumbar cerebrospinal fluid concentrations of somatostatin and neuropeptide Y in multiple sclerosis

    SciTech Connect

    Vecsei, L.; Csala, B.; Widerloev, E.E.; Ekman, R.; Czopf, J.; Palffy, G. (Univ. of Lund (Sweden))

    1990-09-01

    The cerebrospinal fluid (CSF) concentrations of somatostatin and neuropeptide Y were investigated by use of radioimmunoassay in patients suffering from chronic progressive multiple sclerosis. The somatostatin level was significantly decreased in the CSF of patients with multiple sclerosis compared to the control group. The magnitude of this change was more pronounced in patients with severe clinical symptoms of the illness. The CSF neuropeptide Y concentration did not differ from the control values. These findings suggest a selective involvement of somatostatin neurotransmission in multiple sclerosis.

  1. The embryonic blood-cerebrospinal fluid barrier function before the formation of the fetal choroid plexus: role in cerebrospinal fluid formation and homeostasis

    PubMed Central

    Bueno, David; Parvas, Maryam; Garcia-Fernàndez, Jordi

    2014-01-01

    Cerebrospinal fluid (CSF) has attracted interest as an active signaling milieu that regulates brain development, homeostasis, and course disease. CSF is a nutrient-rich fluid, which also contains growth factors and signaling molecules that regulate multiple cell functions in the central nervous system (CNS). CSF constitution is controlled tightly and constituent concentrations are maintained narrow, depending on developmental stage. From fetal stages to adult life, CSF is produced mainly by the choroid plexus. The development and functional activities of the choroid plexus, and other blood-brain barrier systems in adults, have been extensively analyzed. However, the study of CSF production and homeostasis in embryos from the closure of the anterior neuropore, when the brain cavities become physiologically sealed, to the formation of the functional fetal choroid plexus has been largely neglected. This developmental stage is characterized by tightly controlled morphological and cellular events in the anterior part of the CNS, such as rapid brain anlagen growth and initiation of primary neurogenesis in the neural progenitor cells lining the cavities, events which are driven by specific molecules contained within the embryonic CSF. In this article, we review the existing literature on formation and function of the temporary embryonic blood-CSF barrier, from closure of the anterior neuropore to the formation of functional fetal choroid plexuses, with regard to crucial roles that embryonic CSF plays in neural development. PMID:25165045

  2. In vivo phage display screen for peptide sequences that cross the blood-cerebrospinal-fluid barrier.

    PubMed

    Li, Jingwei; Feng, Liang; Jiang, Xinguo

    2015-02-01

    There is lack of a barrier between CSF and brain, thus peptide that can cross the blood-cerebrospinal-fluid barrier (BCSFB) will have a greater chance of providing access to the brain. In this study, we screened for a novel peptide sequence that can cross the BCSFB from the systemic circulation using phage display. We applied a 12-mer phage display peptide library (Ph.D.-12) intravenously in rats and recovered phage from the cerebrospinal fluid. A longer circulation time was used according to the biodistributive CSF/blood ratio of the phage particles. Following sequential rounds of isolation, several phages were sequenced, and a peptide sequence (TPSYDTYAAELR, referred to as the TPS peptide) was identified. Clone 12-1, which encoded the TPS peptide, was enriched approximately 53 times greater than the random library phage. After labeling with FITC, the TPS peptide demonstrated significantly greater brain accumulation efficiency. This study demonstrates the feasibility of using in vivo phage display to screen for peptides that can cross the BCSFB from the systemic circulation. In conclusion, the TPS peptide represents a previously unreported promising motif that can be used to design a drug delivery system that can cross the BCSFB. PMID:25408466

  3. Cerebrospinal fluid lavage in the treatment of inadvertent intrathecal vincristine injection.

    PubMed

    Al Ferayan, A; Russell, N A; Al Wohaibi, M; Awada, A; Scherman, B

    1999-03-01

    Vincristine, a widely used antineoplastic agent, is extremely toxic to the central nervous system. If given intrathecally, it produces a rapidly ascending, usually fatal, neuromyeloencephalopathy. We report a case of this complication in a 7-year-old girl with acute lymphoblastic leukemia who was receiving maintenance chemotherapy. During one treatment 0.5 mg of vincristine was erroneously injected into the lumbar subarachnoid space. Cerebrospinal fluid lavage was established within 2 h and continued for 24 h. After 7 days she developed a progressive sensorimotor paraplegia, which eventually stabilized as a paraparesis. Neurophysiological studies were consistent with an axonal type sensorimotor neuropathy. Magnetic resonance imaging of the spine was normal. Vincristine binds to cells, blocking mitosis, thus causing cell death. The associated central nervous system lesions are those of an ascending chemical leptomeningitis and ventriculitis. Cerebrospinal fluid lavage dilutes and removes the drug, thus limiting neural damage. At present this is the only treatment for intrathecal vincristine injection, and its early use in such an event is considered mandatory. PMID:10230662

  4. Cerebrospinal fluid ?-synuclein predicts cognitive decline in Parkinson disease progression in the DATATOP cohort.

    PubMed

    Stewart, Tessandra; Liu, Changqin; Ginghina, Carmen; Cain, Kevin C; Auinger, Peggy; Cholerton, Brenna; Shi, Min; Zhang, Jing

    2014-04-01

    Most patients with Parkinson disease (PD) develop both cognitive and motor impairment, and biomarkers for progression are urgently needed. Although ?-synuclein is altered in cerebrospinal fluid of patients with PD, it is not known whether it predicts motor or cognitive deterioration. We examined clinical data and ?-synuclein in >300 unmedicated patients with PD who participated in the deprenyl and tocopherol antioxidative therapy of parkinsonism (DATATOP) study, with up to 8 years of follow-up. Longitudinal measures of motor and cognitive function were studied before (phase 1) and during (phase 2) levodopa therapy; cerebrospinal fluid was collected at the beginning of each phase. Correlations and linear mixed models were used to assess ?-synuclein association with disease severity and prediction of progression in the subsequent follow-up period. Despite decreasing ?-synuclein (phase 1 to phase 2 change of -0.05 ± 0.21 log-transformed values, P < 0.001), no correlations were observed between ?-synuclein and motor symptoms. Longitudinally, lower ?-synuclein predicted better preservation of cognitive function by several measures [Selective Reminding Test total recall ?-synuclein × time interaction effect coefficient, -0.12 (P = 0.037); delayed recall, -0.05 (P = 0.002); New Dot Test, -0.03 (P = 0.002)]. Thus, ?-synuclein, although not clinically useful for motor progression, might predict cognitive decline, and future longitudinal studies should include this outcome for further validation. PMID:24625392

  5. Lipocalin 2 in cerebrospinal fluid as a marker of acute bacterial meningitis

    PubMed Central

    2014-01-01

    Background Early differential diagnosis between acute bacterial and viral meningitis is problematic. We aimed to investigate whether the detection of lipocalin 2, a protein of the acute innate immunity response, may be used as a marker for acute bacterial meningitis. Methods Transgenic mice expressing the human transferrin were infected by intraperitoneal route and were imaged. Cerebrospinal fluid (CSF) was sampled up to 48hours post- infection to measure lipocalin 2. We also tested a collection of 90 and 44 human CSF with confirmed acute bacterial or acute viral meningitis respectively. Results Lipocalin 2 was detected after 5 h in CSF during experimental infection in mice. Lipocalin 2 levels were significantly higher (p?cerebrospinal fluid may discriminate between acute bacterial and viral meningitis in patients with clinical syndrome of meningitis. PMID:24885531

  6. Cerebrospinal fluid pharmacology: an improved pharmacology approach for chinese herbal medicine research.

    PubMed

    Wu, Yan-Qing; Zhou, Ying-Wu; Qin, Xiu-de; Hua, Sheng-Yu; Zhang, Yu-Lian; Kang, Li-Yuan

    2013-01-01

    Despite many successful applications of Chinese herbal medicine (CHM) in the treatment and prevention of neurological diseases (ND), the fully scientific understanding of CHM's action mechanisms had been hampered for lack of appropriate methods to explore the combinatorial rules, the synergistic mechanisms, and the molecular basis of CHM. As an improved pharmacology approach, cerebrospinal fluid pharmacology (CSFP), based on the fact that cerebrospinal fluid plays an important role in the health maintenance of specific survival environment for neurons and glial cells, has been constructed and applied to CHM research for treating ND. In the present review, the concept and advantages of CSFP are briefly introduced. The approaches and key technologies of CSFP in CHM research are also collated and analyzed. Furthermore, the developing tendency of CSFP is summarized, and its framework in CHM research is also proposed. In summary, CSFP provides a new strategy not only to eliminate some barriers of CHM research for treating ND, but also to broaden the pharmacology research for bridging the gap between CHM and modern medicine. Moreover, the advancements in CSFP will bring about a conceptual move in active ingredients discovery of CHM and make a significant contribution to CHM modernization and globalization. PMID:24454505

  7. The Th1 versus Th2 cytokine profile in cerebrospinal fluid after severe traumatic brain injury in infants and children.

    PubMed

    Amick, Jonathan E.; Yandora, Kristin A.; Bell, Michael J.; Wisniewski, Stephen R.; Adelson, P. David; Carcillo, Joseph A.; Janesko, Keri L.; DeKosky, Steven T.; Carlos, Timothy M.; Clark, Robert S.B.; Kochanek, Patrick M.

    2001-07-01

    OBJECTIVE: To further characterize the Th1 (proinflammatory) vs. the Th2 (antiinflammatory) cytokine profile after severe traumatic brain injury (TBI) by quantifying the ventricular cerebrospinal fluid concentrations of Th1 cytokines (interleukin [IL]-2 and IL-12) and Th2 cytokines (IL-6 and IL-12) in infants and children. DESIGN: Retrospective study. SETTING: University children's hospital. PATIENTS: Twenty-four children hospitalized with severe TBI (admission Glasgow Coma Scale score, <13) and 12 controls with negative diagnostic lumbar punctures. INTERVENTIONS: All TBI patients received standard neurointensive care, including the placement of an intraventricular catheter for continuous drainage of cerebrospinal fluid. MEASUREMENTS AND MAIN RESULTS: Ventricular cerebrospinal fluid samples (n = 105) were collected for as long as the catheters were in place (between 4 hrs and 222 hrs after TBI). Cerebrospinal fluid samples were analyzed for IL-2, IL-4, IL-6, and IL-12 concentrations by enzyme-linked immunoassay. Peak and mean IL-6 (335.7 +/- 41.4 pg/mL and 259.5 +/- 37.6 pg/mL, respectively) and IL-12 (11.4 +/- 2.2 pg/mL and 4.3 +/- 0.8 pg/mL, respectively) concentrations were increased (p <.05) in children after TBI vs. controls (2.3 +/- 0.7 pg/mL and 1.0 +/- 0.5 pg/mL) for IL-6 and IL-12, respectively. In contrast, peak and mean IL-2 and IL-4 concentrations were not increased in TBI children vs. controls. Increases in the cerebrospinal fluid concentration of IL-6 were significantly associated with admission Glasgow Coma Scale score of cerebrospinal fluid IL-4 and IL-12 were associated with child abuse as an injury mechanism (both p cerebrospinal fluid after TBI in infants and children. It is the first report of increased IL-12 levels in cerebrospinal fluid after TBI in infants and children. Further, it is the first to report on IL-2 and IL-4 levels in pediatric or adult TBI. These data suggest that selected members of both the Th1 and Th2 cytokine families are increased as part of the endogenous inflammatory response to TBI. Finally, in that both IL-6 and IL-12 (but neither IL-2 nor IL-4) can be produced by astrocytes and/or neurons, a parenchymal source for cytokines in the brain after TBI may be critical to their production in the acute phase after TBI. PMID:12793952

  8. How yawning switches the default-mode network to the attentional network by activating the cerebrospinal fluid flow.

    PubMed

    Walusinski, Olivier

    2014-03-01

    Yawning is a behavior to which little research has been devoted. However, its purpose has not yet been demonstrated and remains controversial. In this article, we propose a new theory involving the brain network that is functional during the resting state, that is, the default mode network. When this network is active, yawning manifests a process of switching to the attentional system through its capacity to increase circulation of cerebrospinal fluid (CSF), thereby increasing clearance of somnogenic factors (prostaglandin D(2), adenosine, and others) accumulating in the cerebrospinal fluid. PMID:23813685

  9. Factors affecting the detection of enteroviruses in cerebrospinal fluid with coxsackievirus B3 and poliovirus 1 cDNA probes.

    PubMed Central

    Rotbart, H A; Levin, M J; Villarreal, L P; Tracy, S M; Semler, B L; Wimmer, E

    1985-01-01

    Enteroviruses are common pathogens of meningitis and encephalitis, and infections are often difficult to distinguish clinically from bacterial and herpetic infections of the central nervous system. An array of enteroviruses added to cerebrospinal fluid in reconstruction experiments were detected by a dot hybridization assay. Optimal handling and processing conditions for infected cerebrospinal fluid were established, and the effect on the hybridization reaction of humoral and cellular components of the inflammatory response was determined. Six hybridization probes, derived from poliovirus 1 and coxsackievirus B3, were then tested, singly and in combinations, to optimize the sensitivity and spectrum of the assay. Implications for enteroviral taxonomy based on these experiments are discussed. Images PMID:2993351

  10. Gas Chromatography-Mass Spectrometry-Based Metabolic Profiling of Cerebrospinal Fluid from Epileptic Dogs

    PubMed Central

    HASEGAWA, Tetsuya; SUMITA, Maho; HORITANI, Yusuke; TAMAI, Reo; TANAKA, Katsuhiro; KOMORI, Masayuki; TAKENAKA, Shigeo

    2013-01-01

    ABSTRACT Epilepsy is a common neurological disorder with seizures, but diagnostic approaches in veterinary clinics remain limited. Cerebrospinal fluid (CSF) is a body fluid used for diagnosis in veterinary medicine. In this study, we explored canine epilepsy diagnostic biomarkers using gas chromatography-mass spectrometry (GC-MS)-based metabolic profiling of CSF and multivariate data analysis. Profiles for subjects with idiopathic epilepsy differed significantly from those of healthy controls and subjects with symptomatic epilepsy. Among 60 identified metabolites, the levels of 20 differed significantly among the three groups. Glutamic acid was significantly increased in idiopathic epilepsy, and some metabolites including ascorbic acid were changed in both forms of epilepsy. These findings show that metabolic profiles of CSF differ between idiopathic and symptomatic epilepsy and that metabolites including glutamic acid and ascorbic acid in CSF may be useful for diagnosis of canine epilepsy. PMID:24334864

  11. Physical characteristics in the new model of the cerebrospinal fluid system.

    PubMed

    Jurjevi?, Ivana; Rados, Milan; Oreskovi?, Janko; Priji?, Radovan; Tvrdei?, Ante; Klarica, Marijan

    2011-01-01

    It is unknown which factors determine the changes in cerebrospinal fluid (CSF) pressure inside the craniospinal system during the changes of the body position. To test this, we have developed a new model of the CSF system, which by its biophysical characteristics and dimensions imitates the CSF system in cats. The results obtained on a model were compared to those in animals observed during changes of body position. A new model was constructed from two parts with different physical characteristics. The "cranial" part is developed from a plastic tube with unchangeable volume, while the "spinal" part is made of a rubber baloon, with modulus of elasticity similar to that of animal spinal dura. In upright position, in the "cranial" part of the model the negative pressure appears without any measurable changes in the fluid volume, while in "spinal" part the fluid pressure is positive. All of the observed changes are in accordance to the law of the fluid mechanics. Alterations of the CSF pressure in cats during the changes of the body position are not significantly different compared to those observed on our new model. This suggests that the CSF pressure changes are related to the fluid mechanics, and do not depend on CSF secretion and circulation. It seems that in all body positions the cranial volume of blood and CSF remains constant, which enables a good blood brain perfusion. PMID:21648311

  12. Tau in cerebrospinal fluids: establishment of the sandwich ELISA with antibody specific to the repeat sequence in tau

    Microsoft Academic Search

    Hirosi Mori; Kenji Hosoda; Etsuro Matsubara; Tadakatsu Nakamoto; Yoshiko Furiya; Riuko Endoh; Mihoko Usami; Mikio Shoji; Shoichi Maruyama; Shunsaku Hirai

    1995-01-01

    Clinical diagnosis for Alzheimer's disease (AD) is provided by the criteria of DSMIV and clinical progress in addition to imaging analysis with MRI after negative screening. The final exclusive diagnosis iis confirmed by the neuropathological findings of neurofibrillary tangles and senile plaques in autopsy brains. We developed a new ELISA system to measure the amount of tau in cerebrospinal fluids

  13. Quantification of tau phosphorylated at threonine 181 in human cerebrospinal fluid: a sandwich ELISA with a synthetic phosphopeptide for standardization

    Microsoft Academic Search

    E Vanmechelen; H Vanderstichele; P Davidsson; E Van Kerschaver; B Van Der Perre; M Sjögren; N Andreasen; K Blennow

    2000-01-01

    Hyperphosphorylation of the microtubule-associated protein tau is specifically found in those brain cells affected in several tauopathies. Tau has also been consistently found to be present in the cerebrospinal fluid (CSF). Here we report the quantification in CSF of tau phosphorylated at Thr 181 using an immunoassay with a synthetic peptide for standardization. The choice of the peptide was based

  14. The influence of coughing on cerebrospinal fluid pressure in an in vitro syringomyelia model with spinal subarachnoid space stenosis

    Microsoft Academic Search

    Bryn A Martin; Francis Loth

    2009-01-01

    BACKGROUND: The influence of coughing, on the biomechanical environment in the spinal subarachnoid space (SAS) in the presence of a cerebrospinal fluid flow stenosis, is thought to be an important etiological factor in craniospinal disorders, including syringomyelia (SM), Chiari I malformation, and hydrocephalus. The aim of this study was to investigate SAS and syrinx pressures during simulated coughing using in

  15. Effects of Age on Cerebrospinal Fluid Oxytocin Levels in Free-Ranging Adult Female and Infant Rhesus Macaques

    E-print Network

    Maestripieri, Dario

    Effects of Age on Cerebrospinal Fluid Oxytocin Levels in Free-Ranging Adult Female and Infant as plasma cortisol levels. CSF oxytocin concentrations ranged from 36.02 to 134.41 pg/ml in adult females were positively correlated with adult female age and negatively correlated with infant age. The former

  16. Quantitation of herpes simplex virus DNA in cerebrospinal fluid of patients with herpes simplex encephalitis by the polymerase chain reaction

    Microsoft Academic Search

    M. Grazia Revello; Fausto Baldanti; Antonella Sarasini; Davide Zella; Maurizio Zavattoni; Giuseppe Gerna

    1997-01-01

    Background: Previous studies have shown the diagnostic utility of qualitative detection of herpes simplex virus (HSV) DNA by the polymerase chain reaction (PCR) in cerebrospinal fluid samples (CSF) from patients with herpes simplex encephalitis (HSE).Objectives: To determine whether quantitation of HSV DNA in CSF could be useful for monitoring efficacy of antiviral therapy and provide prognostic indications.Study design: A quantitative

  17. Variable foraging demand rearing: sustained elevations in cisternal cerebrospinal fluid corticotropin-releasing factor concentrations in adult primates

    Microsoft Academic Search

    Jeremy D Coplan; E. L. P Smith; Margaret Altemus; Bruce A Scharf; Michael J Owens; Charles B Nemeroff; Jack M Gorman; Leonard A Rosenblum

    2001-01-01

    Background: The authors previously reported elevated cerebrospinal fluid (CSF) corticotropin-releasing factor (CRF) concentrations in juvenile primates nursed by mothers undergoing experimentally imposed unpredictable foraging conditions in comparison to normally reared controls. The purpose of the present study was to determine if these changes would endure into young adulthood.Methods: Cisternal CSF samples were obtained from those unpredictably reared young adult primates

  18. Negative Correlation between Neuropeptide Y Profile in the Cerebrospinal Fluid and Growth Hormone Pulses in the Peripheral Circulation in Goats

    Microsoft Academic Search

    Tomohiro Yonezawa; Kazutaka Mogi; Jun You Li; Ryuji Sako; Noboru Manabe; Keitaro Yamanouchi; Masugi Nishihara

    2010-01-01

    Background\\/Aims: Growth hormone (GH) is secreted in pulsatile fashion, but the involvement of neuropeptides in the generation of GH pulses is not fully understood. The present study was conducted to elucidate the relationship between GH pulses and neuropeptide levels in the cerebrospinal fluid (CSF) of the third ventricle in ovariectomized goats. Methods: CSF and plasma samples were collected every 15

  19. Cerebrospinal Fluid Pressure, Growth, and Hematology in Relation to Retinol Status of the Rat in Acute Vitamin A Deficiency

    Microsoft Academic Search

    JOYCE E. COREY; ANDK. C. HAYES

    In order to produce a model with which to isolate the primary changes associated with vitamin A deficiency in the weanling rat, cerebrospinal fluid (CSF) pressure, body weight gain, and hématologie responses were charac terized in two experiments. In experiment 1, 35 weanling male rats were fed graded intakes of vitamin A for a 5-week comparison method. It was predicted

  20. Relationship between platelet MAO activity and concentrations of 5HIAA and HVA in cerebrospinal fluid in chronic pain patients

    Microsoft Academic Search

    L. v. Knorring; L. Oreland; J. Häggendal; T. Magnusson; B. Almay; F. Johansson

    1986-01-01

    Summary Platelet monoamine oxidase (MAO) activity and concentrations of 5-HIAA and HVA in the cerebrospinal fluid (CSF) were estimated in a series of 54 chronic pain patients. Platelet MAO activity was found to correlate, positively to CSF concentrations of 5-HIAA and HVA, which had been adjusted in order to eliminate the influence of age and body height. However, only the

  1. Coagulation and fibrinolysis in blood and cerebrospinal fluid after aneurysmal subarachnoid haemorrhage: Effect of tranexamic acid (AMCA)

    Microsoft Academic Search

    H. Fodstad; I. M. Nilsson

    1981-01-01

    Summary Serial assays of blood coagulation factors as well as of fibrin\\/fibrinogen degradation products (FDP) and plasminogen activator activity (PA) on fibrin plates in blood and cerebrospinal fluid (CSF) were performed in 41 consecutive patients with recently ruptured cerebral aneurysms, 21 of whom were randomly treated with tranexamic acid (AMCA). Coagulation factors were unaffected by the drug and plasminogen and

  2. Cerebrospinal Fluid (1,3)-?-d-Glucan Detection as an Aid for Diagnosis of Iatrogenic Fungal Meningitis

    PubMed Central

    Lyons, Jennifer L.; Roos, Karen L.; Marr, Kieren A.; Neumann, Henry; Trivedi, Julie B.; Kimbrough, Dorlan J.; Steiner, Lisa; Thakur, Kiran T.; Harrison, Daniel M.

    2013-01-01

    This case series highlights our experience with use of the Fungitell assay for quantifying (1,3)-?-d-glucan in cerebrospinal fluid during the current U.S. outbreak of fungal meningitis related to contaminated methylprednisolone acetate. This test may prove a useful adjunct in diagnosis and management of exposed patients. PMID:23363831

  3. Asymmetrical Dimethylarginine Is Increased in Plasma and Decreased in Cerebrospinal Fluid of Patients with Alzheimer’s Disease

    Microsoft Academic Search

    Sönke Arlt; Friedrich Schulze; Martin Eichenlaub; Renke Maas; Jan T. Lehmbeck; Edzard Schwedhelm; Holger Jahn; Rainer H. Böger

    2008-01-01

    Background: Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase and may alter NO production during pathological conditions. Concerning Alzheimer’s disease (AD), there are reports on altered cerebral NO metabolism, but only few studies on ADMA concentrations in plasma and cerebrospinal fluid (CSF). Methods: We assessed plasma ADMA in 80 AD patients and 80 age- and gender-matched

  4. Decreased cerebrospinal fluid flow through the central canal of the spinal cord of rats immunologically deprived of Reissner's fibre

    Microsoft Academic Search

    M. Cifuentes; S. Rodríguez; J. Pérez; J. M. Grondona; E. M. Rodríguez; P. Fernández-Llebrez

    1994-01-01

    The subcommissural organ is an ependymal brain gland that secretes glycoproteins to the cerebrospinal fluid (CSF) of the thrid ventricle. They condense to form a fibre, Reissner's fibre (RF), that runs along the aqueduct and fourth ventricle and the central canal of the spinal cord. A single injection of an antibody against the secretory glycoproteins of RF into a lateral

  5. Increases in cerebrospinal fluid caffeine concentration are associated with favorable outcome after severe traumatic brain injury in humans

    Microsoft Academic Search

    Kathleen T Sachse; Edwin K Jackson; Stephen R Wisniewski; Delbert G Gillespie; Ava M Puccio; Robert S B Clark; C Edward Dixon; Patrick M Kochanek

    2008-01-01

    Caffeine, the most widely consumed psychoactive drug and a weak adenosine receptor antagonist, can be neuroprotective or neurotoxic depending on the experimental model or neurologic disorder. However, its contribution to pathophysiology and outcome in traumatic brain injury (TBI) in humans is undefined. We assessed serial cerebrospinal fluid (CSF) concentrations of caffeine and its metabolites (theobromine, paraxanthine, and theophylline) by high-pressure

  6. Diagnostic significance of tau protein in cerebrospinal fluid from patients with corticobasal degeneration or progressive supranuclear palsy

    Microsoft Academic Search

    K. Urakami; K. Wada; H. Arai; H. Sasaki; M. Kanai; M. Shoji; H. Ishizu; K. Kashihara; M. Yamamoto; K. Tsuchiya-Ikemoto; M. Morimatsu; H. Takashima; M. Nakagawa; K. Kurokawa; H. Maruyama; Y. Kaseda; S. Nakamura; K. Hasegawa; H. Oono; C. Hikasa; K. Ikeda; K. Yamagata; Y. Wakutani; T. Takeshima; K. Nakashima

    2001-01-01

    Distinguishing corticobasal degeneration (CBD) from progressive supranuclear palsy (PSP) is clinically and pathologically difficult, and a useful biological marker to discriminative these two diseases has been a subject of clinical interest. In the present study, we assessed tau protein levels in cerebrospinal fluids by sandwich ELISA to distinguish CBD from PSP. The subjects consisted of 27 cases of CBD, 30

  7. Detection of Neisseria meningitidis from Negative Blood Cultures and Cerebrospinal Fluid with the FilmArray Blood Culture Identification Panel

    PubMed Central

    Pardo, Joe; Klinker, Kenneth P.; Borgert, Samuel J.; Butler, Brittany M.; Rand, Kenneth H.

    2014-01-01

    The FilmArray blood culture identification (BCID) panel is a rapid molecular diagnostic test approved for use with positive blood culture material. We describe a fatal case of meningococcemia with central nervous system (CNS) involvement detected using the BCID test with culture-negative blood and cerebrospinal fluid. PMID:24740076

  8. Inverse relationship between beta-endorphin immunoreactivity in cerebrospinal fluid and nucleus tractus solitarius in sudden infant death

    Microsoft Academic Search

    Hanne Storm; Torleiv O. Rognum; Karl L. Reichelt

    1994-01-01

    In nucleus tractus solitarius (NTS) beta-endorphin (BEND) induces bradycardia and respiratory depression which have been reported to precede death in sudden infant death (SID). Of SID victims, 50% have elevated levels of beta-endorphin immunoreactivity (BENDI) in the cerebrospinal fluid (CSF), and 50% had undetectable levels. We therefore investigated the relationship of BENDI in the CSF to BENDI levels in the

  9. The formation and circulation of cerebrospinal fluid inside the cat brain ventricles: a fact or an illusion?

    Microsoft Academic Search

    Darko Oreškovi?; Marijan Klarica; Miroslav Vuki?

    2002-01-01

    Formation and circulation of cerebrospinal fluid (CSF) have been studied in the isolated brain ventricles of anesthetized cats by a new approach and under direct observation. A plastic cannula was introduced into the aqueduct of Sylvius through the vermis cerebelli and the outflow of CSF from the cannula was used as the CSF formation and circulation index. During the 60

  10. New experimental model of acute aqueductal blockage in cats: Effects on cerebrospinal fluid pressure and the size of brain ventricles

    Microsoft Academic Search

    M. Klarica; D. Oreškovi?; B. Boži?; M. Vuki?; V. Butkovi?; M. Bulat

    2009-01-01

    It is generally assumed that cerebrospinal fluid (CSF) is secreted in the brain ventricles, and so after an acute blockage of the aqueduct of Sylvius an increase in the ventricular CSF pressure and dilation of isolated ventricles may be expected. We have tested this hypothesis in cats. After blocking the aqueduct, we measured the CSF pressure in both isolated ventricles

  11. Abnormal glycine metabolism in motor neurone disease: studies on plasma and cerebrospinal fluid.

    PubMed Central

    Lane, R J; Bandopadhyay, R; de Belleroche, J

    1993-01-01

    Plasma amino acid levels were measured following oral glycine loading in 43 patients with motor neurone disease (MND), eight normal subjects and 18 neurological disease controls with wasting or spasticity from a variety of other causes. Levels at baseline and 1.5 h after loading did not differ, but at 4 h, plasma glycine levels in MND patients remained significantly higher than in normal and neurological controls (P < 0.013). Cerebrospinal fluid glycine levels, which were maximal at 2.5 h, were also significantly higher in MND patients than neurological controls (P < 0.04). These observations suggest a defect of glycine 'housekeeping' in the central nervous system in MND which may be relevant to the pathogenesis of the disease. PMID:8410884

  12. From relative to absolute quantification of tryptic peptides with tandem mass tags: application to cerebrospinal fluid.

    PubMed

    Dayon, Loïc; Turck, Natacha; Scherl, Alexander; Hochstrasser, Denis F; Burkhard, Pierre R; Sanchez, Jean-Charles

    2010-01-01

    Quantification is a major task in proteomics. Among the different analytical strategies to enable peptide and protein quantification, tagging with isotopic labels has emerged as a practical, versatile, and efficient alternative. In particular, isobaric labels, such as TMT or iTRAQ, are now widely employed to make relative comparison of the protein amounts in separate biological samples with tandem mass spectrometry (MS/MS). We used herein a shotgun proteomic approach based on labelling with tandem mass tags (TMTs) for the relative quantification of proteins, and the absolute quantification of their tryptic peptides in human cerebrospinal fluid (CSF). First, the comparison of ante- and post-mortem CSF samples was carried out for the discovery of protein marker candidates of brain-damage disorders. Second, tryptic peptides representative of these candidates were measured in CSF using reporter-ion calibration curves. These works highlighted the advantages and limitations of such strategies for quantification purposes in proteomics. PMID:21140904

  13. Detection of anti-heat shock protein 90 beta (Hsp90beta) antibodies in cerebrospinal fluid.

    PubMed

    Cid, C; García-Villanueva, M; Salinas, M; Alcázar, A

    2007-01-10

    Antibodies against heat shock protein 90 beta (Hsp90beta) recognize the antigen on the cell surface of the oligodendrocyte precursor cells and cause a decrease of oligodendrocyte population in cell cultures. These antibodies have been found in patients with multiple sclerosis (MS). This report describes an original and sensitive method to detect anti-Hsp90beta antibodies in cerebrospinal fluid (CSF) using a western blot procedure. We have developed the method for autoantibody detection using Hsp90beta from cell membrane fraction instead of commercial Hsp90beta as antigen. The presence of anti-Hsp90beta antibodies in CSF of MS patients may play a pathogenic role in MS, and a large-scale study is needed to establish a possible diagnostic value of these antibodies in MS patients. PMID:17112536

  14. Quantification of Amino Acid Neurotransmitters in Cerebrospinal Fluid of Patients with Neurocysticercosis

    PubMed Central

    Camargo, José Augusto; Bertolucci, Paulo Henrique Ferreira

    2015-01-01

    Background : Neurocysticercosis is a parasitic disease that affects the central nervous system. Its main clinical manifestations are epileptic seizures. The objective of this study was to investigate the correlation between neurotransmitter concentrations in cerebrospinal fluid (CSF) and the different evolutive forms of neurocysticercosis with or without seizures. Methods : Neurotransmitter concentrations (Aspartate, Glutamate, GABA, Glutamine, Glycine, Taurine) were determined in CSF samples from 42 patients with neurocysticercosis divided into patients with the active cystic form (n = 24, 12 with and 12 without seizures) and patients with calcified form (n = 18, 12 with and 6 without seizures), and a control group consisting of 59 healthy subjects. Results : Alterations in amino acid concentration were observed in all patients with neurocysticercosis. Conclusion : We conclude that disturbances in amino acid metabolism accompany the presentation of neurocysticercosis. Replacement of the terms inactive cyst by reactive inactive cyst and calcification by reactive calcification is suggested. PMID:26157521

  15. Different Levels of HIV DNA Copy Numbers in Cerebrospinal Fluid Cellular Subsets

    PubMed Central

    Agsalda-Garcia, Melissa; Shiramizu, Bruce; Melendez, Loyda; Plaud, Marines; Liang, Chin-Yuan; Wojna, Valerie

    2013-01-01

    Inequities in the incidence of HIV infection and AIDS with associated continued persistence of HIV-associated neurocognitive disorders (HAND) exist in populations in Hawaii (HI) and PR. We previously reported that peripheral monocyte HIV DNA levels are high in patients in Hawaii with HAND and we now hypothesize that similar findings would be observed in the cerebrospinal fluid (CSF) cellular subsets. CSF cells were obtained from patients undergoing neurocognitive testing from PR and HI and sorted into monocytes (CD14+) and lymphocytes (CD14?) and HIV DNA measured. From 6 PR subjects (3 HAND, 3 normal cognition, NC) and 6 HI subjects (3 HAND, 3 NC), HIV DNA burden in CD14+ cells was higher in HAND than NC patients; NC patients had higher HIV DNA burden in CD14? cells versus HAND. Differences in HIV DNA burden in particular CSF cellular subsets suggest that HIV DNA burden may play a role in HAND neuropathogenesis. PMID:24241256

  16. Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE

    PubMed Central

    Ayton, Scott; Faux, Noel G.; Bush, Ashley I.; Weiner, Michael W.; Aisen, Paul; Petersen, Ronald; Jack Jr., Clifford R.; Jagust, William; Trojanowki, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Shaw, Leslie M.; Khachaturian, Zaven; Sorensen, Greg; Kuller, Lew; Raichle, Marc; Paul, Steven; Davies, Peter; Fillit, Howard; Hefti, Franz; Holtzman, Davie; Marcel Mesulam, M.; Potter, William; Snyder, Peter; Schwartz, Adam; Montine, Tom; Thomas, Ronald G.; Donohue, Michael; Walter, Sarah; Gessert, Devon; Sather, Tamie; Jiminez, Gus; Harvey, Danielle; Bernstein, Matthew; Fox, Nick; Thompson, Paul; Schuff, Norbert; Borowski, Bret; Gunter, Jeff; Senjem, Matt; Vemuri, Prashanthi; Jones, David; Kantarci, Kejal; Ward, Chad; Koeppe, Robert A.; Foster, Norm; Reiman, Eric M.; Chen, Kewei; Mathis, Chet; Landau, Susan; Cairns, Nigel J.; Householder, Erin; Taylor-Reinwald, Lisa; Lee, Virginia; Korecka, Magdalena; Figurski, Michal; Crawford, Karen; Neu, Scott; Foroud, Tatiana M.; Potkin, Steven; Shen, Li; Faber, Kelley; Kim, Sungeun; Nho, Kwangsik; Thal, Leon; Buckholtz, Neil; Albert, Marylyn; Frank, Richard; Hsiao, John; Kaye, Jeffrey; Quinn, Joseph; Lind, Betty; Carter, Raina; Dolen, Sara; Schneider, Lon S.; Pawluczyk, Sonia; Beccera, Mauricio; Teodoro, Liberty; Spann, Bryan M.; Brewer, James; Vanderswag, Helen; Fleisher, Adam; Heidebrink, Judith L.; Lord, Joanne L.; Mason, Sara S.; Albers, Colleen S.; Knopman, David; Johnson, Kris; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Rountree, Susan; Dang, Mimi; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Ances, Beau; Carroll, Maria; Leon, Sue; Mintun, Mark A.; Schneider, Stacy; Oliver, Angela; Marson, Daniel; Griffith, Randall; Clark, David; Geldmacher, David; Brockington, John; Roberson, Erik; Grossman, Hillel; Mitsis, Effie; deToledo-Morrell, Leyla; Shah, Raj C.; Duara, Ranjan; Varon, Daniel; Greig, Maria T.; Roberts, Peggy; Albert, Marilyn; Onyike, Chiadi; D'Agostino II, Daniel; Kielb, Stephanie; Galvin, James E.; Cerbone, Brittany; Michel, Christina A.; Rusinek, Henry; de Leon, Mony J; Glodzik, Lidia; De Santi, Susan; Murali Doraiswamy, P.; Petrella, Jeffrey R.; Wong, Terence Z.; Arnold, Steven E.; Karlawish, Jason H.; Wolk, David; Smith, Charles D.; Jicha, Greg; Hardy, Peter; Sinha, Partha; Oates, Elizabeth; Conrad, Gary; Lopez, Oscar L.; Oakley, MaryAnn; Simpson, Donna M.; Porsteinsson, Anton P.; Goldstein, Bonnie S.; Martin, Kim; Makino, Kelly M.; Saleem Ismail, M.; Brand, Connie; Mulnard, Ruth A.; Thai, Gaby; Mc-Adams-Ortiz, Catherine; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Diaz-Arrastia, Ramon; King, Richard; Weiner, Myron; Martin-Cook, Kristen; DeVous, Michael; Levey, Allan I.; Lah, James J.; Cellar, Janet S.; Burns, Jeffrey M.; Anderson, Heather S.; Swerdlow, Russell H.; Apostolova, Liana; Tingus, Kathleen; Woo, Ellen; Silverman, Daniel H.S.; Lu, Po H.; Bartzokis, George; Graff-Radford, Neill R; Parfitt, Francine; Kendall, Tracy; Johnson, Heather; Farlow, Martin R.; Hake, Ann Marie; Matthews, Brandy R.; Herring, Scott; Hunt, Cynthia; van Dyck, Christopher H.; Carson, Richard E.; MacAvoy, Martha G.; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Robin Hsiung, Ging-Yuek; Feldman, Howard; Mudge, Benita; Assaly, Michele; Kertesz, Andrew; Rogers, John; Bernick, Charles; Munic, Donna; Kerwin, Diana; Mesulam, Marek-Marsel; Lipowski, Kristine; Wu, Chuang-Kuo; Johnson, Nancy; Sadowsky, Carl; Martinez, Walter; Villena, Teresa; Scott Turner, Raymond; Johnson, Kathleen; Reynolds, Brigid; Sperling, Reisa A.; Johnson, Keith A.; Marshall, Gad; Frey, Meghan; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Sabbagh, Marwan N.; Belden, Christine M.; Jacobson, Sandra A.; Sirrel, Sherye A.; Kowall, Neil; Killiany, Ronald; Budson, Andrew E.; Norbash, Alexander; Johnson, Patricia Lynn; Allard, Joanne; Lerner, Alan; Ogrocki, Paula; Hudson, Leon; Fletcher, Evan; Carmichael, Owen; Olichney, John; DeCarli, Charles; Kittur, Smita; Borrie, Michael; Lee, T-Y; Bartha, Rob; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Potkin, Steven G.; Preda, Adrian; Nguyen, Dana; Tariot, Pierre; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Scharre, Douglas W.; Kataki, Maria; Adeli, Anahita; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Pearlson, Godfrey D.; Blank, Karen; Anderson, Karen; Santulli, Robert B.; Kitzmiller, Tamar J.; Schwartz, Eben S.; Sink, Kaycee M.; Williamson, Jeff D.; Garg, Pradeep; Watkins, Franklin; Ott, Brian R.; Querfurth, Henry; Tremont, Geoffrey

    2015-01-01

    Brain iron elevation is implicated in Alzheimer's disease (AD) pathogenesis, but the impact of iron on disease outcomes has not been previously explored in a longitudinal study. Ferritin is the major iron storage protein of the body; by using cerebrospinal fluid (CSF) levels of ferritin as an index, we explored whether brain iron status impacts longitudinal outcomes in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We show that baseline CSF ferritin levels were negatively associated with cognitive performance over 7 years in 91 cognitively normal, 144 mild cognitive impairment (MCI) and 67 AD subjects, and predicted MCI conversion to AD. Ferritin was strongly associated with CSF apolipoprotein E levels and was elevated by the Alzheimer's risk allele, APOE-?4. These findings reveal that elevated brain iron adversely impacts on AD progression, and introduce brain iron elevation as a possible mechanism for APOE-?4 being the major genetic risk factor for AD. PMID:25988319

  17. Identification of Biomarkers in Cerebrospinal Fluid and Serum of Multiple Sclerosis Patients by Immunoproteomics Approach

    PubMed Central

    Colomba, Paolo; Fontana, Simona; Salemi, Giuseppe; Barranca, Marilisa; Lo Sicco, Claudia; Mazzola, Maria Antonietta; Ragonese, Paolo; Savettieri, Giovanni; De Leo, Giacomo; Alessandro, Riccardo; Duro, Giovanni

    2014-01-01

    Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system. At present, the molecular mechanisms causing the initiation, development and progression of MS are poorly understood, and no reliable proteinaceous disease markers are available. In this study, we used an immunoproteomics approach to identify autoreactive antibodies in the cerebrospinal fluid of MS patients to use as candidate markers with potential diagnostic value. We identified an autoreactive anti-transferrin antibody that may have a potential link with the development and progression of MS. We found this antibody at high levels also in the serum of MS patients and created an immunoenzymatic assay to detect it. Because of the complexity and heterogeneity of multiple sclerosis, it is difficult to find a single marker for all of the processes involved in the origin and progression of the disease, so the development of a panel of biomarkers is desirable, and anti-transferrin antibody could be one of these. PMID:25517032

  18. Resistance to outflow of cerebrospinal fluid after central infusions of angiotensin

    NASA Technical Reports Server (NTRS)

    Morrow, B. A.; Keil, L. C.; Severs, W. B.

    1992-01-01

    Infusions of artificial cerebrospinal fluid (CSF) into the cerebroventricles of conscious rats can raise CSF pressure (CSFp). This response can be modified by some neuropeptides. One of these, angiotensin, facilitates the rise in CSFp. We measured CSFp in conscious rats with a computerized system and evaluated resistance to CSF outflow during infusion of artificial CSF, with or without angiotensin, from the decay kinetics of superimposed bolus injections. Angiotensin (10 ng/min) raised CSFp (P less than 0.05) compared with solvent, but the resistance to CSF outflow of the two groups was similar (P greater than 0.05). Because CSFp was increased by angiotensin without an increase in the outflow resistance, a change in some volume compartment is likely. Angiotensin may raise CSFp by increasing CSF synthesis; this possibility is supported, since the choroid plexuses contain an intrinsic isorenin-angiotensin system. Alternatively, angiotensin may dilate pial arteries, leading to an increased intracranial blood volume.

  19. Identification and characterization of immune complexes in the cerebrospinal fluid of patients with spinal cord schistosomiasis.

    PubMed

    Ferrari, Teresa C A; Faria, Luciana C; Vilaça, Tatiane S; Correa, Cristiane R; Góes, Alfredo M

    2011-01-01

    The pathogenesis of neuroschistosomiasis is largely unknown. Available evidence suggests that it depends on the presence of parasite eggs in the nervous tissue and on the host's immune response. We investigated the presence of immune complexes (ICs) in the cerebrospinal fluid (CSF) of four patients with spinal cord schistosomiasis (SCS), and performed their characterization. ICs containing soluble egg antigen of Schistosoma mansoni (SEA) were found in the CSF of all the SCS patients. To our knowledge, this is the first evidence of ICs containing schistosomal antigens in the CSF of patients with SCS. Further studies are necessary to confirm our findings and investigate the possible roles of ICs in the pathogenesis of this disease. PMID:20850875

  20. Portable lactate analyzer for measuring lactate in cerebrospinal fluid (CSF) and plasma – method-comparison evaluations

    PubMed Central

    de Almeida, Sérgio Monteiro; Marquie-Beck, Jennifer; Bhatt, Archana; Letendre, Scott; McCutchan, Allen; Ellis, Ron

    2014-01-01

    Increased plasma lactate levels can indicate the presence of metabolic disorders in HIV infected individuals. Objective To determine whether a portable analyzer is valid for measuring cerebrospinal fluid (CSF) and plasma lactate levels in HIV infected individuals. Method CSF and plasma were collected from 178 subjects. Samples tested by the Accutrend® portable analyzer were compared to those tested by a reference device (SYNCHRON LX® 20). Results The portable analyzer had in plasma sensitivity of 0.95 and specificity 0.87. For CSF the specificity was 0.95; the sensitivity 0.33; the negative predictive value was 95% and the positive predictive value 33%. Conclusions These findings support the validity of the portable analyzer in measuring lactate concentrations in CSF that fall within the normal range. The relatively poor positive predictive value indicates that a result above the reference range may represent a “false positive test”, and should be confirmed by the reference device before concluding abnormality. PMID:25054981

  1. Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE.

    PubMed

    Ayton, Scott; Faux, Noel G; Bush, Ashley I

    2015-01-01

    Brain iron elevation is implicated in Alzheimer's disease (AD) pathogenesis, but the impact of iron on disease outcomes has not been previously explored in a longitudinal study. Ferritin is the major iron storage protein of the body; by using cerebrospinal fluid (CSF) levels of ferritin as an index, we explored whether brain iron status impacts longitudinal outcomes in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We show that baseline CSF ferritin levels were negatively associated with cognitive performance over 7 years in 91 cognitively normal, 144 mild cognitive impairment (MCI) and 67 AD subjects, and predicted MCI conversion to AD. Ferritin was strongly associated with CSF apolipoprotein E levels and was elevated by the Alzheimer's risk allele, APOE-?4. These findings reveal that elevated brain iron adversely impacts on AD progression, and introduce brain iron elevation as a possible mechanism for APOE-?4 being the major genetic risk factor for AD. PMID:25988319

  2. Reduction of PrPC in human cerebrospinal fluid after spinal cord injury

    PubMed Central

    Carnini, Anna; Casha, Steve; Yong, V. Wee; Hurlbert, R. John

    2010-01-01

    It has been estimated that cerebrospinal fluid (CS F) contains approximately 80 proteins that significantly increase or decrease in response to various clinical conditions. Here we have evaluated the CS F protein PrPC (cellular prion protein) for possible increases or decreases following spinal cord injury. The physiological function of PrPC is not yet completely understood; however, recent findings suggest that PrPC may have neuroprotective properties. Our results show that CS F PrPC is decreased in spinal cord injured patients 12 h following injury and is absent at 7 days. Given that normal PrPC has been proposed to be neuroprotective, we speculate that the decrease in CS F PrPC levels may influence neuronal cell survival following spinal cord injury. PMID:20418657

  3. Detection of High Cerebrospinal Fluid Levels of (1?3)-?-d-Glucan in Cryptococcal Meningitis

    PubMed Central

    Rhein, Joshua; Bahr, Nathan C.; Morawski, Bozena M.; Schutz, Charlotte; Zhang, Yonglong; Finkelman, Malcolm; Meya, David B.; Meintjes, Graeme; Boulware, David R.

    2014-01-01

    Background ?(1?3)-?-d-Glucan (BDG) is a helpful diagnostic marker for many invasive fungal infections. However, BDG is not thought to be useful in diagnosing cryptococcosis. We evaluated the utility of BDG as an adjunct diagnostic tool for patients infected with human immunodeficiency virus (HIV) and presenting with suspected cryptococcal meningitis. Methods ?The Fungitell assay was used to measure BDG concentrations in cerebrospinal fluid (CSF) (n = 177) and serum (n = 109) of HIV-infected Ugandans and South Africans with suspected meningitis. Correlations between BDG concentrations and quantitative CSF cryptococcal cultures, CSF cryptococcal antigen (CRAG) titers, and 18 different CSF cytokine concentrations were assessed using non-parametric tests. Mixed models evaluated longitudinal changes in CSF BDG concentrations. Survival analyses were used to evaluate BDG's relationship with mortality. Results ?The Fungitell BDG assay provided 89% sensitivity and 85% specificity in CSF for cryptococcal meningitis. Serum sensitivity was suboptimal (79%). Cerebrospinal fluid BDG concentrations at diagnosis were median (interquartile range) 343 (200–597) pg/mL in cryptococcal patients and 37 (23–46) pg/mL in patients without cryptococcosis. Sensitivity in CSF improved to 98% (53 of 54) when initial fungal burdens were ?10 000 colony-forming units/mL. (1?3)-?-d-Glucan normalized rapidly after initiating antifungal therapy. Baseline BDG concentrations correlated with CSF fungal burden (rho = 0.820; P < .001), CSF CRAG lateral flow assay titers (rho = 0.780, P < .001), and monocyte chemotactic protein-1 levels in CSF (P = .047). In patients with cryptococcal meningitis, BDG ?500 pg/mL at diagnosis was associated with increased 10-week mortality. Conclusions ?(1?3)-?-d-Glucan is detectable in the CSF of HIV-infected patients with Cryptococcus, and it may provide useful prognostic information. Sensitivity is less than CRAG; however, BDG normalizes rapidly, unlike CRAG, making BDG potentially useful in diagnosing recurrent episodes. PMID:25734173

  4. Neurofilament Light Chain Levels in Ventricular Cerebrospinal Fluid Following Acute Aneurysmal Subarachnoid Hemorrhage

    PubMed Central

    Zanier, Elisa R.; Refai, Daniel; Zipfel, Gregory J.; Zoerle, Tommaso; Longhi, Luca; Esparza, Thomas J.; Spinner, Michael L.; Bateman, Randall J.; Brody, David L.; Stocchetti, Nino

    2013-01-01

    Purpose The contribution of axonal injury to brain damage following aneurysmal subarachnoid hemorrhage (aSAH) is unknown. Neurofilament light chain (NF-L), a component of the axonal cytoskeleton, has been shown to be elevated in the cerebrospinal fluid of patients with many types of axonal injury. We hypothesized that patients with aSAH would have elevated CSF NF-L levels, and sought to explore the clinical correlates of CSF NF-L dynamics. Methods Serial ventricular cerebrospinal fluid (vCSF) samples were collected from 35 aSAH patients for up to 15 days. vCSF NF-L measurements were determined by enzyme-linked immunosorbent assay. NF-L levels were analyzed in relation to acute clinical status, radiological findings, and 6-month outcomes. Results vCSF NF-L concentrations were elevated in all aSAH patients. Patients with early cerebral ischemia (ECI), defined as a CT hypodense lesion visible within the first 3 days, had higher acute vCSF NF-L levels than patients without ECI. These elevated NF-L levels were similar in patients with ECI associated with intracranial hemorrhage and ECI associated with surgical/endovascular complications. vCSF NF-L levels did not differ as a function of acute clinical status, clinical vasospasm, delayed cerebral ischemia, or 6-month Glasgow Outcome Scale. Conclusions Elevated vCSF NF-L levels may in part reflect increased injury to axons associated with early cerebral ischemia. However our results suggest that axonal injury following aSAH as reflected by release of NF-L into the CSF may not play a major role in either secondary adverse events or long term clinical outcomes. PMID:20571038

  5. miRNA contents of cerebrospinal fluid extracellular vesicles in glioblastoma patients

    PubMed Central

    Akers, Johnny C.; Ramakrishnan, Valya; Kim, Ryan; Phillips, Shirley; Kaimal, Vivek; Mao, Ying; Hua, Wei; Yang, Isaac; Fu, Chia-Chun; Nolan, John; Nakano, Ichiro; Yang, Yuanfan; Beaulieu, Martin; Carter, Bob S.; Chen, Clark C.

    2015-01-01

    Introduction Analysis of extracellular vesicles (EVs) derived from plasma or cerebrospinal fluid (CSF) has emerged as a promising biomarker platform for therapeutic monitoring in glioblastoma patients. However, the contents of the various subpopulations of EVs in these clinical specimens remain poorly defined. Here we characterize the relative abundance of miRNA species in EVs derived from the serum and cerebrospinal fluid of glioblastoma patients. Methods EVs were isolated from glioblastoma cell lines as well as the plasma and CSF of glioblastoma patients. The microvesicle subpopulation was isolated by pelleting at 10,000×g for 30 min after cellular debris was cleared by a 2,000×g (20 min) spin. The exosome subpopulation was isolated by pelleting the microvesicle supernatant at 120,000×g (120 min). qRT-PCR was performed to examine the distribution of miR-21, miR-103, miR-24, and miR-125. Global miRNA profiling was performed in select glioblastoma CSF samples. Results In plasma and cell line derived EVs, the relative abundance of miRNAs in exosome and microvesicles were highly variable. In some specimens, the majority of the miRNA species were found in exosomes while in other, they were found in microvesicles. In contrast, CSF exosomes were enriched for miRNAs relative to CSF microvesicles. In CSF, there is an average of one molecule of miRNA per 150-25,000 EVs. Conclusion Most EVs derived from clinical biofluids are devoid of miRNA content. The relative distribution of miRNA species in plasma exosomes or microvesicles is unpredictable. In contrast, CSF exosomes are the major EV compartment that harbor miRNAs. PMID:25903655

  6. Pharmacokinetics of methotrexate in the cerebrospinal fluid after intracerebroventricular administration in patients with meningeal carcinomatosis and altered cerebrospinal fluid flow dynamics

    SciTech Connect

    Miller, K.T.; Wilkinson, D.S.

    1989-01-01

    Pharmacokinetic parameters of the distribution and elimination of intracerebroventricularly administered methotrexate (MTX) were evaluated in three patients with meningeal carcinomatosis. Abnormal cerebrospinal fluid (CSF) flow dynamics, which were not otherwise clinically evident, were diagnosed by 111In-diethylenetriaminepentaacetate radionuclide imaging. Alterations in CSF flow resulted in large changes in MTX distribution. Reduced cortical convexity (type III), spinal subarachnoid (type II), or ventricular (type I) CSF flow resulted in a prolongation of the single-pass mean residence time of MTX in the peripheral compartment by as much as eightfold and a reduction in intercompartmental clearance by 94-99%. Leptomeningeal carcinomatosis can affect both CSF MTX distribution and elimination, each to a different extent, within the same patient. Total MTX clearance from the CSF was reduced by 79-93% in the patients studied. A two-compartment pharmacokinetic model, with elimination occurring from the peripheral compartment, gave values for the distribution rate constant from the central to the peripheral compartment (k12), which decreased with the extent of CSF flow abnormality. However, the elimination rate constant from the peripheral compartment (k20) was reduced to an extent apparently independent of CSF flow abnormality (percentage reduction in k12 and k20, respectively: type III, 18 and 66; type II, 67 and 86; type I, 78 and 48). Inadequate distribution and locally high concentrations of MTX within the CSF may contribute to therapeutic failure and neurotoxicity. Monitoring of MTX levels in the CSF may be deceiving when samples are drawn from the site of injection, since the distribution kinetics are altered by abnormal CSF flow dynamics.

  7. Sphingolipid Metabolism Correlates with Cerebrospinal Fluid Beta Amyloid Levels in Alzheimer’s Disease

    PubMed Central

    Fonteh, Alfred N.; Ormseth, Cora; Chiang, Jiarong; Cipolla, Matthew; Arakaki, Xianghong; Harrington, Michael G.

    2015-01-01

    Sphingolipids are important in many brain functions but their role in Alzheimer’s disease (AD) is not completely defined. A major limit is availability of fresh brain tissue with defined AD pathology. The discovery that cerebrospinal fluid (CSF) contains abundant nanoparticles that include synaptic vesicles and large dense core vesicles offer an accessible sample to study these organelles, while the supernatant fluid allows study of brain interstitial metabolism. Our objective was to characterize sphingolipids in nanoparticles representative of membrane vesicle metabolism, and in supernatant fluid representative of interstitial metabolism from study participants with varying levels of cognitive dysfunction. We recently described the recruitment, diagnosis, and CSF collection from cognitively normal or impaired study participants. Using liquid chromatography tandem mass spectrometry, we report that cognitively normal participants had measureable levels of sphingomyelin, ceramide, and dihydroceramide species, but that their distribution differed between nanoparticles and supernatant fluid, and further differed in those with cognitive impairment. In CSF from AD compared with cognitively normal participants: a) total sphingomyelin levels were lower in nanoparticles and supernatant fluid; b) levels of ceramide species were lower in nanoparticles and higher in supernatant fluid; c) three sphingomyelin species were reduced in the nanoparticle fraction. Moreover, three sphingomyelin species in the nanoparticle fraction were lower in mild cognitive impairment compared with cognitively normal participants. The activity of acid, but not neutral sphingomyelinase was significantly reduced in the CSF from AD participants. The reduction in acid sphingomylinase in CSF from AD participants was independent of depression and psychotropic medications. Acid sphingomyelinase activity positively correlated with amyloid ?42 concentration in CSF from cognitively normal but not impaired participants. In dementia, altered sphingolipid metabolism, decreased acid sphingomyelinase activity and its lost association with CSF amyloid ?42 concentration, underscores the potential of sphingolipids as disease biomarkers, and acid sphingomyelinase as a target for AD diagnosis and/or treatment. PMID:25938590

  8. Affinity proteomic profiling of plasma, cerebrospinal fluid, and brain tissue within multiple sclerosis.

    PubMed

    Byström, Sanna; Ayoglu, Burcu; Häggmark, Anna; Mitsios, Nicholas; Hong, Mun-Gwan; Drobin, Kimi; Forsström, Björn; Fredolini, Claudia; Khademi, Mohsen; Amor, Sandra; Uhlén, Mathias; Olsson, Tomas; Mulder, Jan; Nilsson, Peter; Schwenk, Jochen M

    2014-11-01

    The brain is a vital organ and because it is well shielded from the outside environment, possibilities for noninvasive analysis are often limited. Instead, fluids taken from the spinal cord or circulatory system are preferred sources for the discovery of candidate markers within neurological diseases. In the context of multiple sclerosis (MS), we applied an affinity proteomic strategy and screened 22 plasma samples with 4595 antibodies (3450 genes) on bead arrays, then defined 375 antibodies (334 genes) for targeted analysis in a set of 172 samples and finally used 101 antibodies (43 genes) on 443 plasma as well as 573 cerebrospinal spinal fluid (CSF) samples. This revealed alteration of protein profiles in relation to MS subtypes for IRF8, IL7, METTL14, SLC30A7, and GAP43. Respective antibodies were subsequently used for immunofluorescence on human post-mortem brain tissue with MS pathology for expression and association analysis. There, antibodies for IRF8, IL7, and METTL14 stained neurons in proximity of lesions, which highlighted these candidate protein targets for further studies within MS and brain tissue. The affinity proteomic translation of profiles discovered by profiling human body fluids and tissue provides a powerful strategy to suggest additional candidates to studies of neurological disorders. PMID:25231264

  9. Cisterna magna microdialysis of sup 22 Na to evaluate ion transport and cerebrospinal fluid dynamics

    SciTech Connect

    Knuckey, N.W.; Fowler, A.G.; Johanson, C.E.; Nashold, J.R.; Epstein, M.H. (Brown Univ./Rhode Island Hospital, Providence (USA))

    1991-06-01

    Microdialysis is used in vivo for measuring compounds in brain interstitial fluid. The authors describe another application of this technique to the central nervous system, namely microprobe dialysis in the cisterna magna to study the dynamics of ion transport and cerebrospinal fluid (CSF) formation in the rat. The choroid plexus is the major source of CSF, which is produced by active transport of Na from blood into the cerebral ventricles. Formation of CSF is directly proportional to the blood-to-CSF transport of Na. By injecting {sup 22}Na into the systemic circulation and quantifying its movement into CSF by microdialysis, one can reliably estimate alterations in the rate of CSF formation. The sensitivity of this system was determined by administering acetazolamide, a standard inhibitor of CSF production. Because acetazolamide is known to decrease CSF formation by 40% to 50%, the cisternal microdialysis system in animals treated with this drug should detect a corresponding decrease in the amount of {sup 22}Na dialyzed. This hypothesis is supported by the {sup 22}Na uptake curves for control versus treated animals: that is, by the acetazolamide-induced average diminution of about 45% in both the rate and extent of tracer accession to dialysate. Bumetanide, a loop diuretic, reduced by 30% the {sup 22}Na entry into dialysate. Microprobe dialysis of fluid in the cisterna magna is thus a minimally invasive and economical method for evaluating effects of drugs and hormones on the choroid plexus-CSF system.

  10. Effects of irregular cerebrospinal fluid production rate in human brain ventricular system

    NASA Astrophysics Data System (ADS)

    Hadzri, Edi Azali; Shamsudin, Amir Hamzah; Osman, Kahar; Abdul Kadir, Mohammed Rafiq; Aziz, Azian Abd

    2012-06-01

    Hydrocephalus is an abnormal accumulation of fluid in the ventricles and cavities in the brain. It occurs when the cerebrospinal fluid (CSF) flow or absorption is blocked or when excessive CSF is secreted. The excessive accumulation of CSF results in an abnormal widening of the ventricles. This widening creates potentially harmful pressure on the tissues of the brain. In this study, flow analysis of CSF was conducted on a three-dimensional model of the third ventricle and aqueduct of Sylvius, derived from MRI scans. CSF was modeled as Newtonian Fluid and its flow through the region of interest (ROI) was done using EFD. Lab software. Different steady flow rates through the Foramen of Monro, classified by normal and hydrocephalus cases, were modeled to investigate its effects. The results show that, for normal and hydrocephalus cases, the pressure drop of CSF flow across the third ventricle was observed to be linearly proportionally to the production rate increment. In conclusion, flow rates that cause pressure drop of 5 Pa was found to be the threshold for the initial sign of hydrocephalus.

  11. Amyloid beta binding proteins in vitro and in normal human cerebrospinal fluid.

    PubMed

    Golabek, A; Marques, M A; Lalowski, M; Wisniewski, T

    1995-05-19

    A major neuropathological feature of Alzheimer's disease (AD) is the deposition of amyloid beta (A beta) in the form of senile plaques. The A beta peptide exists both in a beta-pleated sheet fibrillar form in amyloid deposits and as a normal soluble protein in biological fluids. Numerous proteins have been identified immunohistochemically to be associated with senile plaques, where A beta is the major constituent. Some of the latter have also been suggested to be carriers of the normal soluble A beta (sA beta) including apolipoprotein J (apoJ), apolipoprotein E (apoE) and transthyretin (TTR). We have found, using several different methods, that numerous proteins can bind synthetic A beta peptides when high concentrations are used; however, using an affinity anti-sA beta column we confirm that apoJ is the major binding protein in pooled human cerebrospinal fluid. On the other hand it is known that apoE co-purifies with A beta biochemically extracted from senile plaques. In AD tissue there may be a change in the major apolipoprotein binding A beta from apoJ to apoE. PMID:7659297

  12. Detection of Protein Aggregates in Brain and Cerebrospinal Fluid Derived from Multiple Sclerosis Patients

    PubMed Central

    David, Monique Antoinette; Tayebi, Mourad

    2014-01-01

    Studies of the properties of soluble oligomer species of amyloidogenic proteins, derived from different proteins with little sequence homology, have indicated that they share a common structure and may share similar pathogenic mechanisms. Amyloid ?, tau protein, as well as amyloid precursor protein normally associated with Alzheimer’s disease and Parkinson’s disease were found in lesions and plaques of multiple sclerosis patients. The objective of the study is to investigate whether brain and cerebrospinal fluid (CSF) samples derived from multiple sclerosis patients demonstrate the presence of soluble oligomers normally associated with protein-misfolding diseases such as Alzheimer’s disease. We have used anti-oligomer monoclonal antibodies to immunodetect soluble oligomers in CSF and brain tissues derived from multiple sclerosis patients. In this report, we describe the presence of soluble oligomers in the brain tissue and cerebral spinal fluid of multiple sclerosis patients detected with our monoclonal anti-oligomer antibodies with Western blot and Sandwich enzyme-linked immunosorbent assay (sELISA). These results might suggest that protein aggregation plays a role in multiple sclerosis pathogenesis although further and more refined studies are needed to confirm the role of soluble aggregates in multiple sclerosis. PMID:25520699

  13. Flow induced by ependymal cilia dominates near-wall cerebrospinal fluid dynamics in the lateral ventricles

    PubMed Central

    Siyahhan, Bercan; Knobloch, Verena; de Zélicourt, Diane; Asgari, Mahdi; Schmid Daners, Marianne; Poulikakos, Dimos; Kurtcuoglu, Vartan

    2014-01-01

    While there is growing experimental evidence that cerebrospinal fluid (CSF) flow induced by the beating of ependymal cilia is an important factor for neuronal guidance, the respective contribution of vascular pulsation-driven macroscale oscillatory CSF flow remains unclear. This work uses computational fluid dynamics to elucidate the interplay between macroscale and cilia-induced CSF flows and their relative impact on near-wall dynamics. Physiological macroscale CSF dynamics are simulated in the ventricular space using subject-specific anatomy, wall motion and choroid plexus pulsations derived from magnetic resonance imaging. Near-wall flow is quantified in two subdomains selected from the right lateral ventricle, for which dynamic boundary conditions are extracted from the macroscale simulations. When cilia are neglected, CSF pulsation leads to periodic flow reversals along the ventricular surface, resulting in close to zero time-averaged force on the ventricle wall. The cilia promote more aligned wall shear stresses that are on average two orders of magnitude larger compared with those produced by macroscopic pulsatile flow. These findings indicate that CSF flow-mediated neuronal guidance is likely to be dominated by the action of the ependymal cilia in the lateral ventricles, whereas CSF dynamics in the centre regions of the ventricles is driven predominantly by wall motion and choroid plexus pulsation. PMID:24621815

  14. The role of cerebrospinal fluid pressure in glaucoma and other ophthalmic diseases: A review

    PubMed Central

    Fleischman, David; Allingham, R. Rand

    2013-01-01

    Glaucoma is one of the most common causes of blindness in the world. Well-known risk factors include age, race, a positive family history and elevated intraocular pressures. A newly proposed risk factor is decreased cerebrospinal fluid pressure (CSFP). This concept is based on the notion that a pressure differential exists across the lamina cribrosa, which separates the intraocular space from the subarachnoid fluid space. In this construct, an increased translaminar pressure difference will occur with a relative increase in elevated intraocular pressure or a reduction in CSFP. This net change in pressure is proposed to act on the tissues within the optic nerve head, potentially contributing to glaucomatous optic neuropathy. Similarly, patients with ocular hypertension who have elevated CSFPs, would enjoy a relatively protective effect from glaucomatous damage. This review will focus on the current literature pertaining to the role of CSFP in glaucoma. Additionally, the authors examine the relationship between glaucoma and other known CSFP-related ophthalmic disorders. PMID:24227969

  15. Plasma and cerebrospinal fluid pharmacokinetics of acivicin in Ommaya reservoir-bearing rhesus monkeys.

    PubMed

    McGovren, J P; Stewart, J C; Elfring, G L; Smith, R B; Soares, N; Wood, J H; Poplack, D G; Von Hoff, D D

    1982-06-01

    Acivicin was administered iv to rhesus monkeys bearing Ommaya reservoirs, and serial blood and cerebrospinal fluid (CSF) samples were collected and analyzed to determine the time course of drug concentrations in these body fluids. After iv doses of 4 or 20 mg/kg (50 or 250 mg/m2), acivicin plasma concentrations demonstrated a rapid initial decline (distribution phase), and then declined exponentially with a terminal (elimination phase) half-life of 3--4 hrs. CSF concentrations increased over a period of 2--2.5 hrs, reaching peak values of 2.0--2.7 micrograms/ml at 20 mg/kg and 0.3--0.5 microgram/ml at 4 mg/kg; thereafter, CSF levels declined in parallel with plasma, with a CSF/plasma concentration ratio of 0.10--0.17. A three-compartment pharmacokinetic model gave a close fit of predicted and observed plasma and CSF concentration data. Significant and predictable CSF penetration by iv administered acivicin in monkeys is consistent with observation of CNS side effects in patients in the phase I clinical trial and suggests that acivicin should be evaluated in the treatment of CNS malignancies and metastases. PMID:7083237

  16. Development of hydrocephalus and classical hypothesis of cerebrospinal fluid hydrodynamics: facts and illusions.

    PubMed

    Oreškovi?, D; Klarica, M

    2011-08-01

    According to the classical hypothesis of the cerebrospinal fluid (CSF) hydrodynamics, CSF is produced inside the brain ventricles, than it circulates like a slow river toward the cortical subarachnoid space, and finally it is absorbed into the venous sinuses. Some pathological conditions, primarily hydrocephalus, have also been interpreted based on this hypothesis. The development of hydrocephalus is explained as an imbalance between CSF formation and absorption, where more CSF is formed than is absorbed, which results in an abnormal increase in the CSF volume inside the cranial CSF spaces. It is believed that the reason for the imbalance is the obstruction of the CSF pathways between the site of CSF formation and the site of its absorption, which diminishes or prevents CSF outflow from the cranium. In spite of the general acceptance of the classical hypothesis, there are a considerable number of experimental results that do not support such a hypothesis and the generally accepted pathophysiology of hydrocephalus. A recently proposed new working hypothesis suggests that osmotic and hydrostatic forces at the central nervous system microvessels are crucial for the regulation of interstial fluid and CSF volume which constitute a functional unit. Based on that hypothesis, the generally accepted mechanisms of hydrocephalus development are not plausible. Therefore, the recent understanding of the correlation between CSF physiology and the development of hydrocephalus has been thoroughly presented, analyzed and evaluated, and new insights into hydrocephalus etiopathology have been proposed, which are in accordance with the experimental data and the new working hypothesis. PMID:21641963

  17. Quantification of the cerebrospinal fluid from a new whole body MRI sequence

    NASA Astrophysics Data System (ADS)

    Lebret, Alain; Petit, Eric; Durning, Bruno; Hodel, Jérôme; Rahmouni, Alain; Decq, Philippe

    2012-03-01

    Our work aims to develop a biomechanical model of hydrocephalus both intended to perform clinical research and to assist the neurosurgeon in diagnosis decisions. Recently, we have defined a new MR imaging sequence based on SPACE (Sampling Perfection with Application optimized Contrast using different flip-angle Evolution). On these images, the cerebrospinal fluid (CSF) appears as a homogeneous hypersignal. Therefore such images are suitable for segmentation and for volume assessment of the CSF. In this paper we present a fully automatic 3D segmentation of such SPACE MRI sequences. We choose a topological approach considering that CSF can be modeled as a simply connected object (i.e. a filled sphere). First an initial object which must be strictly included in the CSF and homotopic to a filled sphere, is determined by using a moment-preserving thresholding. Then a priority function based on an Euclidean distance map is computed in order to control the thickening process that adds "simple points" to the initial thresholded object. A point is called simple if its addition or its suppression does not result in change of topology neither for the object, nor for the background. The method is validated by measuring fluid volume of brain phantoms and by comparing our volume assessments on clinical data to those derived from a segmentation controlled by expert physicians. Then we show that a distinction between pathological cases and healthy adult people can be achieved by a linear discriminant analysis on volumes of the ventricular and intracranial subarachnoid spaces.

  18. Cryptococcal meningitis--a follow-up study of a serious clinical entity: quick cytological and microbiological diagnostics using a special staining procedure in cerebrospinal fluid specimens.

    PubMed

    Adam, P; Sobek, O; Dolezil, D; Lodin, Z; Kasík, J; Hajduková, L; Cihelková, S; Svatonová, J; Hybel'ová, M; Adam, D; Melezinková, V

    2009-11-01

    A routine diagnostic procedure of cryptococcal meningitis using Alcian Blue and Nuclear Fast Red staining is described in a group of 16 patients. Cerebrospinal fluid findings, including clinical cytology, routine biochemistry and protein fractions, are presented. PMID:20140729

  19. Uptake of Melatonin into the Cerebrospinal Fluid After Nasal and Intravenous Delivery: Studies in Rats and Comparison with a Human Study

    Microsoft Academic Search

    Mascha P. van den Berg; Paul Merkus; Stefan G. Romeijn; J. Coos Verhoef; Frans W. H. M. Merkus

    2004-01-01

    Purpose. To investigate the possibility of direct transport of melatonin from the nasal cavity into the cerebrospinal fluid (CSF) after nasal administration in rats and to compare the animal results with a human study.

  20. Body Height, Estimated Cerebrospinal Fluid Pressure and Open-Angle Glaucoma. The Beijing Eye Study 2011

    PubMed Central

    Wang, Ya Xing; You, Qi Sheng; Xie, Xiaobin; Yang, Diya; Xu, Liang

    2014-01-01

    Purpose To examine potential associations between body height, cerebrospinal fluid pressure (CSFP), trans-lamina cribrosa pressure difference (TLCPD) and prevalence of open-angle glaucoma (OAG) in a population-based setting. Methods The population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6±9.8 years (range:50–93 years). A detailed ophthalmic examination was performed. Based on a previous study with lumbar cerebrospinal fluid pressure (CSFP) measurements, CSFP was calculated as CSFP[mmHg]?=?0.44×Body Mass Index[kg/m2]+0.16×Diastolic Blood Pressure[mmHg]-0.18×Age[Years]-1.91 Results Data of IOP and CSFP were available for 3353 (96.7%) subjects. Taller body height was associated with higher CSFP (P<0.001; standardized correlation coefficient beta:0.13; regression coefficient B:0.29; 95% confidence interval (CI):0.25,0.33) after adjusting for male gender, urban region of habitation, higher educational level, and pulse rate. If TLCPD instead of CSFP was added, taller body height was associated with lower TLCPD (P<0.001;beta:?0.10;B:?0.20;95%CI:?0.25,?0.15). Correspondingly, higher CSFP was associated with taller body height (P?=?0.003;beta:0.02;B:0.01;95%CI:0.00,0.02), after adjusting for age, gender, body mass index, pulse, systolic blood pressure, and blood concentration of cholesterol. If IOP was added to the model, higher CSFP was associated with higher IOP (P<0.001;beta:0.02;B:0.02;95%CI:0.01,0.03). TLCPD was associated with lower body height (P?=?0.003;beta:?0.04;B ?0.02,95%CI:?0.04,?0.01) after adjusting for age, body mass index, systolic blood pressure, pulse, blood concentrations of triglycerides, axial length, central corneal thickness, corneal curvature radius, and anterior chamber depth. Adding the prevalence of OAG to the multivariate analysis revealed, that taller body height was associated with a lower OAG prevalence (P?=?0.03;beta:?0.03;B:?1.20;95%CI:?2.28,?0.12) after adjusting for educational level and gender. Conclusions Taller body height was associated with higher CSFP and lower TLCPD (and vice versa), after adjusting for systemic and ocular parameters. Parallel to the associations between a higher prevalence of glaucoma with a lower CSFP or higher TLCPD, taller body height was associated with a lower prevalence of OAG. PMID:24489767

  1. Properties of subependymal cerebrospinal fluid contacting neurones in the dorsal vagal complex of the mouse brainstem

    PubMed Central

    Orts-Del'Immagine, Adeline; Wanaverbecq, Nicolas; Tardivel, Catherine; Tillement, Vanessa; Dallaporta, Michel; Trouslard, Jérôme

    2012-01-01

    Cerebrospinal fluid (CSF) contacting neurones have been observed in various brain regions such as the hypothalamus, the dorsal nucleus of the raphe and around the central canal (cc) of the spinal cord but their functional role remains unclear. At the level of the spinal cord, subependymal cerebrospinal fluid contacting neurones (S-CSF-cNs) present a peculiar morphology with a soma close to the ependymal layer, a process projecting towards the cc and ending with a bud and a cilium. These neurones were recently shown to express polycystin kidney disease 2-like 1 (PKD2L1 or TRPP3) channels that are members of the polycystin subtype of the transient receptor potential (TRP) channel superfamily and that have been proposed as either chemo- or mechanoreceptors in several tissues. Using immunohistological techniques and whole-cell electrophysiological recordings in brain slices obtained from PKD2L1:EGFP transgenic adult mice, we looked for and determined the functional properties of S-CSF-cNs in the dorsal vagal complex (DVC), a hindbrain structure controlling autonomic functions such as blood pressure, energy balance and food intake. Here, we demonstrate that S-CSF-cNs received GABAergic and/or glycinergic synaptic entries and were also characterised by the presence of non-selective cationic channels of large conductance that could be detected even under whole-cell configuration. The channel activity was not affected by Psalmopoeus cambridgei toxin 1, a blocker of acid sensing ion channels (ASICs), but was blocked by amiloride and by a strong extracellular acidification. In contrast, extracellular alkalinisation and hypo-osmotic shocks increased channel activity. Based on these properties, we suggest that the single-channel activity recorded in medullar S-CSF-cNs is carried by PKD2L1 channels. Our study therefore reinforces the idea that PKD2L1 is a marker of S-CSF-cNs and points toward a role for S-CSF-cNs in the detection of circulating signals and of modifications in the extracellular environment. PMID:22570378

  2. Properties of subependymal cerebrospinal fluid contacting neurones in the dorsal vagal complex of the mouse brainstem.

    PubMed

    Orts-Del'immagine, Adeline; Wanaverbecq, Nicolas; Tardivel, Catherine; Tillement, Vanessa; Dallaporta, Michel; Trouslard, Jérôme

    2012-08-15

    Cerebrospinal fluid (CSF) contacting neurones have been observed in various brain regions such as the hypothalamus, the dorsal nucleus of the raphe and around the central canal (cc) of the spinal cord but their functional role remains unclear. At the level of the spinal cord, subependymal cerebrospinal fluid contacting neurones (S-CSF-cNs) present a peculiar morphology with a soma close to the ependymal layer, a process projecting towards the cc and ending with a bud and a cilium. These neurones were recently shown to express polycystin kidney disease 2-like 1 (PKD2L1 or TRPP3) channels that are members of the polycystin subtype of the transient receptor potential (TRP) channel superfamily and that have been proposed as either chemo- or mechanoreceptors in several tissues. Using immunohistological techniques and whole-cell electrophysiological recordings in brain slices obtained from PKD2L1:EGFP transgenic adult mice, we looked for and determined the functional properties of S-CSF-cNs in the dorsal vagal complex (DVC), a hindbrain structure controlling autonomic functions such as blood pressure, energy balance and food intake. Here, we demonstrate that S-CSF-cNs received GABAergic and/or glycinergic synaptic entries and were also characterised by the presence of non-selective cationic channels of large conductance that could be detected even under whole-cell configuration. The channel activity was not affected by Psalmopoeus cambridgei toxin 1, a blocker of acid sensing ion channels (ASICs), but was blocked by amiloride and by a strong extracellular acidification. In contrast, extracellular alkalinisation and hypo-osmotic shocks increased channel activity. Based on these properties, we suggest that the single-channel activity recorded in medullar S-CSF-cNs is carried by PKD2L1 channels. Our study therefore reinforces the idea that PKD2L1 is a marker of S-CSF-cNs and points toward a role for S-CSF-cNs in the detection of circulating signals and of modifications in the extracellular environment. PMID:22570378

  3. Neuraxial anesthesia in patients with intracranial hypertension or cerebrospinal fluid shunting systems: what should the anesthetist know?

    PubMed

    Guerci, P; Vial, F; Mcnelis, U; Losser, M R; Raft, J; Klein, O; Iohom, G; Audibert, G; Bouaziz, H

    2014-09-01

    The management of patients with central nervous system disorders such as brain tumours, hydrocephalus, intracranial hypertension, or subarachnoid hemorrhage has improved in recent years resulting in increased life expectancy. Consequently, the prevalence of patients with increased intracranial pressure or cerebrospinal fluid shunting devices presenting for non-neurological procedures has increased. These patients commonly receive a general anesthetic, as the safety profile of neuraxial anesthesia in this clinical setting remains uncertain. This article reviews literature on neuraxial anesthesia in patients with intracranial hypertension or cerebrospinal fluid shunting systems. It describes current knowledge, exposes and weighs the real benefits and risks of this technique in this setting. It provides several scenarios and anesthetic options to help the practitioner with choosing a tailored approach in this specific population. PMID:24280821

  4. Cerebrospinal Fluid Concentrations of Somatostatin and Biogenic Amines in Grown Primates Reared by Mothers Exposed to Manipulated Foraging Conditions

    Microsoft Academic Search

    Jeremy D. Coplan; Ronald C. Trost; Michael J. Owens; Thomas B. Cooper; Jack M. Gorman; Charles B. Nemeroff; Leonard A. Rosenblum

    1998-01-01

    Background: In an earlier study, infant primates were nursed by mothers randomly assigned to variable forag- ing demand (VFD) or nonvariable foraging conditions (non-VFD). A group of grown VFD-reared subjects demonstrated elevations of cisternal cerebrospinal fluid (CSF) corticotropin-releasing factor concentra- tions and decreased CSF cortisol levels vs non-VFD counterparts. To further characterize neurobiological sequelae of disturbed early rearing, CSF concentrations

  5. Cerebrospinal fluid 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) following probenecid in unipolar depressives treated with amitriptyline

    Microsoft Academic Search

    Malcolm B. Bowers

    1972-01-01

    Lumbar cerebrospinal fluid 5-HIAA, HVA, and the ratio 5-HIAA\\/HVA were measured followed probenecid administration in eleven patints with unipolar depression before and during treatment with amitriptyline (AMI). Control values were obtained from a group of inmate volunteers. Prior to treatment CSF 5HIAA formation in the depressives was not different from controls. During treatment with AMI, CSF 5-HIAA formation decreased. One

  6. Cerebrospinal fluid antibodies to aquaporin-4 in neuromyelitis optica and related disorders: frequency, origin, and diagnostic relevance

    Microsoft Academic Search

    Diego Franciotta; Friedemann Paul; Klemens Ruprecht; Roberto Bergamaschi; Paulus S Rommer; Reinhard Reuss; Christian Probst; Wolfgang Kristoferitsch; Klaus Peter Wandinger; Brigitte Wildemann

    2010-01-01

    BACKGROUND: In 70-80% of cases, neuromyelitis optica (NMO) is associated with highly specific serum auto-antibodies to aquaporin-4 (termed AQP4-Ab or NMO-IgG). Recent evidence strongly suggests that AQP4-Ab are directly involved in the immunopathogenesis of NMO. OBJECTIVE: To assess the frequency, syndrome specificity, diagnostic relevance, and origin of cerebrospinal fluid (CSF) AQP4-Ab in patients with NMO spectrum disorders (NMOSD). METHODS: 87

  7. Effects of Diazepam on Sleep, Temperature, 5-Hydroxyindoleacetic and Homovanillic Acids in Cisternal Cerebrospinal Fluid of Cats

    Microsoft Academic Search

    Mindaugas L. Griauzde; Edwin H. Chen

    1979-01-01

    The effects of diazepam (DZ) (0.3–1.5 mg\\/kg, i.p.) on sleep, cisternal cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), and rectal temperature of cats were examined. The results showed that administration of DZ produced a significant increase (p = 0.02) in slow-wave sleep (SWS) with a peak occurring at a dose of 0.9 mg\\/kg. Further increase

  8. Tumour necrosis factor alpha is elevated in serum and cerebrospinal fluid in multiple sclerosis and inflammatory neuropathies

    Microsoft Academic Search

    M. Rentzos; C. Nikolaou; A. Rombos; K. Voumvourakis; I. Segditsa; C. Papageorgiou

    1996-01-01

    Tumour necrosis factor alpha (TNF?) is a peptide that is derived from T lymphocytes and macrophages and is used as a marker\\u000a of activated cellular immune responses. TNF? was measured in paired sera and cerebrospinal fluid (CSF) from 30 patients with\\u000a multiple sclerosis (MS) with worsening disability, 54 patients with other neurological diseases, and 20 normal subjects. A\\u000a sensitive enzyme-linked

  9. Intraoperative management to prevent cerebrospinal fluid leakage after microvascular decompression: dural closure with a “plugging muscle” method

    Microsoft Academic Search

    Jae Sung Park; Doo-Sik Kong; Jeong-A. Lee; Kwan Park

    2007-01-01

    Our objective is to present surgical techniques used for the prevention of cerebrospinal fluid leakage after microvascular\\u000a decompression (MVD). From January 1996 to February 2006, microvascular decompression for hemifacial spasm or trigeminal neuralgia\\u000a was performed in 678 consecutive patients. In order to achieve watertight dural closure, several pieces of muscle were interposed\\u000a between the dura when the dura was sutured;

  10. Intrathecal 4-Hydroperoxycyclophosphamide: Neurotoxicity, Cerebrospinal Fluid Pharmacokinetics, and Antitumor Activity in a Rabbit Model of VX2 Leptomeningeal Carcinomatosisl

    Microsoft Academic Search

    Peter C. Phillips; Thuy T. Than; Linda C. Cork; John Hilton; Benjamin S. Carson; O. Michael Colvin; Louise B. Grochow

    Dissemination of tumor to the leptomeninges and cerebrospinal fluid represents a common pattern of metastasis for many cancers; however, few chemotherapeutic agents are available for intrathecal (i.t.) use and treatment results are often poor. We studied the neurotoxicity and phar- macokinetics of i.t. 4-hydroperoxycyclophosphamide (4-HC) in the rab bit and the activity of i.t. 4-HC in a VX2 rabbit model

  11. Brain Magnetic Resonance Imaging White-Matter Lesions and Cerebrospinal Fluid Findings in Patients with Acute Intermittent Porphyria

    Microsoft Academic Search

    Ingemar Bylesjö; Ole-Lars Brekke; Jan Prytz; Trine Skjeflo; Rolf Salvesen

    2004-01-01

    Background: Case reports display similaritiesbetween multiple sclerosis and acute intermittent porphyria (AIP). This study examines whether patients with AIP in general demonstrate white-matter lesions on brain magnetic resonance imaging (MRI) and\\/or abnormalities in plasma and\\/or cerebrospinal fluid (CSF) when examined outside attacks. We looked particularly for the presence of oligoclonal bands (OB) of immunoglobulin (Ig) in liquor. Methods:Eight AIP gene

  12. Cerebrospinal fluid 3,4-dihydroxyphenylacetic acid level after tolcapone administration as an indicator of nigrostriatal degeneration

    Microsoft Academic Search

    Christine Thiffault; J. William Langston; Donato A Di Monte

    2003-01-01

    The development of reliable biological markers of nigrostriatal degeneration has important implications from both experimental and clinical viewpoints, since such biomarkers could be used for diagnostic and monitoring purposes in models of parkinsonism as well as in Parkinson’s disease patients. In this study, levels of the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were measured in the cerebrospinal fluid (CSF) of normal

  13. Cerebrospinal fluid from amyotrophic lateral sclerosis has no effect on intracellular free calcium in cultured cortical neurons

    Microsoft Academic Search

    Ole Gredal; Michael Robin Witt; Kim Dekermendjian; Svend Erik Møller; Mogens Nielsen

    1996-01-01

    The data from the literature regarding the presence of a neurotoxic factor in amyotrophic lateral sclerosis (ALS) plasma or\\u000a cerebrospinal fluid (CSF) remain controversial. As a new approach to this question, we have studied the effect of CSF from\\u000a ALS patients on the temporal dynamics of the intracellular free calcium concentration ([Ca2+]i) of murine cortical neurons in cultures using Fura-2

  14. Detection by PCR of Enteroviruses in Cerebrospinal Fluid during a Summer Outbreak of Aseptic Meningitis in Switzerland

    Microsoft Academic Search

    MERI GORGIEVSKI-HRISOHO; JEAN-DANIEL SCHUMACHER; NEVENKA VILIMONOVIC; DANIEL GERMANN; LUKAS MATTER

    1998-01-01

    Enteroviruses (EV) are among the most common causes of aseptic meningitis. Standard diagnostic tech- niques are often too slow and lack sensitivity to be of clinical relevance. EV RNA can be detected withi n5hb y a commercially available reverse transcription-PCR (RT-PCR) test kit. Cerebrospinal fluid (CSF) samples from 68 patients presenting with aseptic meningitis during a summer outbreak in Switzerland

  15. MiRNA profiles in cerebrospinal fluid from patients with central hypersomnias.

    PubMed

    Holm, Anja; Bang-Berthelsen, Claus Heiner; Knudsen, Stine; Modvig, Signe; Kornum, Birgitte Rahbek; Gammeltoft, Steen; Jennum, Poul J

    2014-12-15

    MicroRNAs (miRNAs) are involved in the pathogenesis of many human diseases, including some neurological disorders. Recently, we have reported dysregulated miRNAs in plasma from patients with central hypersomnias including type 1 and type 2 narcolepsy, and idiopathic hypersomnia. This study addressed whether miRNA levels are altered in the cerebrospinal fluid (CSF) of patients with central hypersomnias. We conducted high-throughput analyses of miRNAs in CSF from patients using quantitative real-time polymerase chain reaction panels. We identified 13, 9, and 11 miRNAs with a more than two-fold change in concentration in CSF from patients with type 1 and type 2 narcolepsy and idiopathic hypersomnia, respectively, compared with matched healthy controls. Most miRNAs differed in more than one of the sleep disorders. However, all miRNAs were detected at low levels in CSF and varied between individuals. None of them showed significant differences in concentrations between groups after correcting for multiple testing, and none could be validated in an independent cohort. Nevertheless, approximately 60% of the most abundant miRNAs in the profile reported here have previously been identified in the CSF of healthy individuals, showing consistency with previous miRNA profiles found in CSF. In conclusion, we were not able to demonstrate distinct levels or patterns of miRNAs in CSF from central hypersomnia patients. PMID:25451005

  16. Natural killer cell subsets in cerebrospinal fluid of patients with multiple sclerosis.

    PubMed

    Rodríguez-Martín, E; Picón, C; Costa-Frossard, L; Alenda, R; Sainz de la Maza, S; Roldán, E; Espiño, M; Villar, L M; Álvarez-Cermeño, J C

    2015-05-01

    Changes in blood natural killer (NK) cells, important players of the immune innate system, have been described in multiple sclerosis (MS). We studied percentages and total cell counts of different effector and regulatory NK cells in cerebrospinal fluid (CSF) of MS patients and other neurological diseases to gain clearer knowledge of the role of these cells in neuroinflammation. NK cell subsets were assessed by flow cytometry in CSF of 85 consecutive MS patients (33 with active disease and 52 with stable MS), 16 with other inflammatory diseases of the central nervous system (IND) and 17 with non-inflammatory neurological diseases (NIND). MS patients showed a decrease in percentages of different CSF NK subpopulations compared to the NIND group. However, absolute cell counts showed a significant increase of all NK subsets in MS and IND patients, revealing that the decrease in percentages does not reflect a real reduction of these immune cells. Remarkably, MS patients showed a significant increase of regulatory/effector (CD56(bright) /CD56(dim) ) NK ratio compared to IND and NIND groups. In addition, MS activity associated with an expansion of NK?T cells. These data show that NK cell subsets do not increase uniformly in all inflammatory neurological disease and suggest strongly that regulatory CD56(bright) and NK?T cells may arise in CSF of MS patients as an attempt to counteract the CNS immune activation characteristic of the disease. PMID:25565222

  17. Lipidomic analysis of cerebrospinal fluid by mass spectrometry-based methods.

    PubMed

    Colsch, Benoit; Seyer, Alexandre; Boudah, Samia; Junot, Christophe

    2015-01-01

    Lipids are natural substances found in all living organisms. Essential to the integrity of cell membranes, they also have many biological functions linked to energy storage and cell signaling, and are involved in a large number of heterogeneous diseases such as cancer, diabetes, neurological disorders, and inherited metabolic diseases. Lipids are challenging to analyze because of their huge structural diversity and numerous species. Up to now, lipid analysis has been achieved by targeted approaches focusing on selected families and relying on extraction protocols and chromatographic methods coupled to various detectors including mass spectrometry. Thanks to the technological improvements achieved in the fields of chromatography, high-resolution mass spectrometry and bioinformatics, it is possible to perform global lipidomic analyses enabling the concomitant detection, identification and relative quantification of many lipid species belonging to different families. The aim of this review is to focus on mass spectrometry-based methods to perform lipid and lipidomic analyses and on their application to the analysis of cerebrospinal fluid. PMID:25488626

  18. Neuronal and Glia-Related Biomarkers in Cerebrospinal Fluid of Patients with Acute Ischemic Stroke

    PubMed Central

    Hjalmarsson, Clara; Bjerke, Maria; Andersson, Björn; Blennow, Kaj; Zetterberg, Henrik; Åberg, N David; Olsson, Bob; Eckerström, Carl; Bokemark, Lena; Wallin, Anders

    2014-01-01

    BACKGROUND Cerebral ischemia promotes morphological reactions of the neurons, astrocytes, oligodendrocytes, and microglia in experimental studies. Our aim was to examine the profile of CSF (cerebrospinal fluid) biomarkers and their relation to stroke severity and degree of white matter lesions (WML). METHODS A total of 20 patients (mean age 76 years) were included within 5–10 days after acute ischemic stroke (AIS) onset. Stroke severity was assessed using NIHSS (National Institute of Health stroke scale). The age-related white matter changes (ARWMC) scale was used to evaluate the extent of WML on CT-scans. The concentrations of specific CSF biomarkers were analyzed. RESULTS Patients with AIS had significantly higher levels of NFL (neurofilament, light), T-tau, myelin basic protein (MBP), YKL-40, and glial fibrillary acidic protein (GFAP) compared with controls; T-Tau, MBP, GFAP, and YKL-40 correlated with clinical stroke severity, whereas NFL correlated with severity of WML (tested by Mann–Whitney test). CONCLUSIONS Several CSF biomarkers increase in AIS, and they correlate to clinical stroke severity. However, only NFL was found to be a marker of degree of WML. PMID:24932109

  19. A Luminex assay detects amyloid ? oligomers in Alzheimer's disease cerebrospinal fluid.

    PubMed

    Herskovits, Adrianna Z; Locascio, Joseph J; Peskind, Elaine R; Li, Ge; Hyman, Bradley T

    2013-01-01

    Amyloid beta (a?) protein assembles into larger protein aggregates during the pathogenesis of Alzheimer's disease (AD) and there is increasing evidence that soluble a? oligomers are a critical pathologic species. Diagnostic evaluations rely on the measurement of increased tau and decreased a?42 in the cerebrospinal fluid (CSF) from AD patients and evidence for oligomeric a? in patient CSF is conflicting. In this study, we have adapted a monoclonal single antibody sandwich ELISA assay to a Luminex platform and found that this assay can detect oligomerized a?42 and sAPP? fragments. We evaluated oligomeric a? reactivity in 20 patients with AD relative to 19 age matched controls and compared these values with a commercially available Alzbio3 kit that detects tau, phosphorylated tau and a?42 on the same diagnostic platform. We found that CSF samples of patients with AD had elevated a? oligomers compared to control subjects (p < 0.05) and the ratio of a? oligomers to a?42 was also significantly elevated (p < 0.0001). Further research to develop high sensitivity analytical platforms and rigorous methods of developing stable assay standards will be needed before the analysis of oligomeric a? becomes a routine diagnostic assay for the evaluation of late onset AD patients. PMID:23844122

  20. Plasmacytoid dendritic cells are increased in cerebrospinal fluid of untreated patients during multiple sclerosis relapse.

    PubMed

    Longhini, Ana Leda F; von Glehn, Felipe; Brandão, Carlos Otávio; de Paula, Rosemeire F O; Pradella, Fernando; Moraes, Adriel S; Farias, Alessandro S; Oliveira, Elaine C; Quispe-Cabanillas, Juan G; Abreu, Cassiana Horta; Damasceno, Alfredo; Damasceno, Benito P; Balashov, Konstantin E; Santos, Leonilda M B

    2011-01-01

    The plasmacytoid dendritic cells (pDCs) express a high level of Toll-like receptor 9 (TLR-9), which recognizes viral DNA. Activated via TLR-9, pDCs also secrete large amounts of type I interferon which are involved either in stimulation or down regulation of immune response in multiple sclerosis (MS). In the present study, we determinate pDCs levels by flow cytometry in Cerebrospinal Fluid (CSF) and Peripheral Blood from MS patients in relapsing and in remitting phases of the disease, comparing with other non-inflammatory diseases (OND). We provide evidence that MS patients in relapse without any treatment have a significantly (p < 0.01) higher percentage of pDCs in CSF than do patients in remission or those with OND. No change in the percentage of pDCs was observed in the peripheral blood of any of these patients. The increase of pDCs in central nervous system during relapse may be explained either by a virus infection or a down regulatory process. PMID:21214939

  1. Plasmacytoid dendritic cells are increased in cerebrospinal fluid of untreated patients during multiple sclerosis relapse

    PubMed Central

    2011-01-01

    The plasmacytoid dendritic cells (pDCs) express a high level of Toll-like receptor 9 (TLR-9), which recognizes viral DNA. Activated via TLR-9, pDCs also secrete large amounts of type I interferon which are involved either in stimulation or down regulation of immune response in multiple sclerosis (MS). In the present study, we determinate pDCs levels by flow cytometry in Cerebrospinal Fluid (CSF) and Peripheral Blood from MS patients in relapsing and in remitting phases of the disease, comparing with other non-inflammatory diseases (OND). We provide evidence that MS patients in relapse without any treatment have a significantly (p < 0.01) higher percentage of pDCs in CSF than do patients in remission or those with OND. No change in the percentage of pDCs was observed in the peripheral blood of any of these patients. The increase of pDCs in central nervous system during relapse may be explained either by a virus infection or a down regulatory process. PMID:21214939

  2. Role of cerebrospinal fluid biomarkers in clinical trials for Alzheimer's disease modifying therapies.

    PubMed

    Kang, Ju-Hee; Ryoo, Na-Young; Shin, Dong Wun; Trojanowski, John Q; Shaw, Leslie M

    2014-12-01

    Until now, a disease-modifying therapy (DMT) that has an ability to slow or arrest Alzheimer's disease (AD) progression has not been developed, and all clinical trials involving AD patients enrolled by clinical assessment alone also have not been successful. Given the growing consensus that the DMT is likely to require treatment initiation well before full-blown dementia emerges, the early detection of AD will provide opportunities to successfully identify new drugs that slow the course of AD pathology. Recent advances in early detection of AD and prediction of progression of the disease using various biomarkers, including cerebrospinal fluid (CSF) A?1-42, total tau and p-tau181 levels, and imagining biomarkers, are now being actively integrated into the designs of AD clinical trials. In terms of therapeutic mechanisms, monitoring these markers may be helpful for go/no-go decision making as well as surrogate markers for disease severity or progression. Furthermore, CSF biomarkers can be used as a tool to enrich patients for clinical trials with prospect of increasing statistical power and reducing costs in drug development. However, the standardization of technical aspects of analysis of these biomarkers is an essential prerequisite to the clinical uses. To accomplish this, global efforts are underway to standardize CSF biomarker measurements and a quality control program supported by the Alzheimer's Association. The current review summarizes therapeutic targets of developing drugs in AD pathophysiology, and provides the most recent advances in the. PMID:25598657

  3. Cerebrospinal fluid norepinephrine and cognition in subjects across the adult age span

    PubMed Central

    Wang, Lucy Y.; Murphy, Richard R.; Hanscom, Brett; Li, Ge; Millard, Steven P.; Petrie, Eric C.; Galasko, Douglas R.; Sikkema, Carl; Raskind, Murray A.; Wilkinson, Charles W.; Peskind, Elaine R.

    2013-01-01

    Adequate central nervous system noradrenergic activity enhances cognition, but excessive noradrenergic activity may have adverse effects on cognition. Previous studies have also demonstrated that noradrenergic activity is higher in older than younger adults. We aimed to determine relationships between cerebrospinal fluid (CSF) norepinephrine (NE) concentration and cognitive performance by using data from a CSF bank that includes samples from 258 cognitively normal participants aged 21–100 years. After adjusting for age, gender, education, and ethnicity, higher CSF NE levels (units of 100 pg/mL) are associated with poorer performance on tests of attention, processing speed, and executive function (Trail Making A: regression coefficient 1.5, standard error [SE] 0.77, p = 0.046; Trail Making B: regression coefficient 5.0, SE 2.2, p = 0.024; Stroop Word-Color Interference task: regression coefficient 6.1, SE 2.0, p = 0.003). Findings are consistent with the earlier literature relating excess noradrenergic activity with cognitive impairment. PMID:23639207

  4. Elevated Levels of Cerebrospinal Fluid and Plasma Interleukin-37 in Patients with Guillain-Barré Syndrome

    PubMed Central

    Li, Cong; Zhao, Pingwei; Sun, Xiguang; Che, Yuanyuan; Jiang, Yanfang

    2013-01-01

    Aims. Interleukin-37 (IL-37) is an anti-inflammatory cytokine. This study aims to investigate the concentrations of plasma and cerebrospinal fluid (CSF) IL-37 in patients with Guillain-Barré Syndrome (GBS). Methods. The levels of plasma and CSF IL-37, IL-17A, IFN-?, and TNF-? in 25 GBS patients and 20 healthy controls (HC) were determined by enzyme-linked immunoabsorbent assay and flow cytometric bead array assay, respectively. The values of clinical parameters in the patients were also measured. Results. The concentrations of plasma IL-37, IL-17A, IFN-?, and TNF-? and CSF IL-37 and IL-17A in patients at the acute phase of GBS were significantly higher than those in the HC. The levels of plasma IL-37, IL-17A, IFN-?, and TNF-? were positively correlated in those patients, and the levels of CSF IL-37 and IL-17A as well as the levels of plasma TNF-? were correlated positively with the GBS disability scale scores (GDSs) in those patients. Treatment with intravenous immunoglobulin significantly reduced the levels of plasma IL-37, IL-17A, IFN-?, and TNF-? in the drug-responding patients. Conclusions. Our findings indicate higher levels of plasma and CSF IL-37 and IL-17A and other proinflammatory cytokines in patients with GBS. PMID:24174711

  5. Analysis of cerebrospinal fluid ?-aminobutyric acid by capillary electrophoresis with laser-induced fluorescence detection.

    PubMed

    Casado, Mercedes; Molero, Marta; Sierra, Cristina; García-Cazorla, Angels; Ormazabal, Aida; Artuch, Rafael

    2014-04-01

    The measurement of ?-aminobutyric acid (GABA) is suitable for investigating various neurological disorders. In this study, a sensitive and selective method for free GABA quantification in cerebrospinal fluid (CSF) has been standardised. This method is based on CE with LIF detection using 4-fluoro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-F) as a derivatisating agent. The reaction conditions (NBD-F concentration, pH, temperature and reaction time) and the electrophoretic parameters (run buffer composition and pH and separation voltage) were optimised to obtain the maximum derivatisation efficiency and electrophoretic resolution. The best resolution was obtained using 200 mM sodium borate, 10 mM SDS, 8.5 mM ?-CD, pH 10 and 20 kV voltage. The method was linear in the concentration range of 2.5-1000 nM with good inter- and intra-assay precision values. The effects of CSF handling on free GABA concentrations were also evaluated. Our results show that the time delay between CSF collection and freezing strongly increases the CSF GABA values. Age-related reference values were established in 55 paediatric controls. The influence of antiepileptic therapy on free CSF GABA was studied in 38 neuropaediatric patients. Significantly, higher GABA values were obtained in patients taking valproic acid or vigabatrin therapy, which are antiepileptic drugs that modulate GABA metabolism. PMID:24338894

  6. Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer's disease.

    PubMed

    Blennow, Kaj; Dubois, Bruno; Fagan, Anne M; Lewczuk, Piotr; de Leon, Mony J; Hampel, Harald

    2015-01-01

    Several potential disease-modifying drugs for Alzheimer's disease (AD) have failed to show any effect on disease progression in clinical trials, conceivably because the AD subjects are already too advanced to derive clinical benefit from treatment and because diagnosis based on clinical criteria alone introduces a high misdiagnosis rate. Thus, well-validated biomarkers for early detection and accurate diagnosis are crucial. Low cerebrospinal fluid (CSF) concentrations of the amyloid-? (A?1-42) peptide, in combination with high total tau and phosphorylated tau, are sensitive and specific biomarkers highly predictive of progression to AD dementia in patients with mild cognitive impairment. However, interlaboratory variations in the results seen with currently available immunoassays are of concern. Recent worldwide standardization efforts and quality control programs include standard operating procedures for both preanalytical (e.g., lumbar puncture and sample handling) and analytical (e.g., preparation of calibration curve) procedures. Efforts are also ongoing to develop highly reproducible assays on fully automated instruments. These global standardization and harmonization measures will provide the basis for the generalized international application of CSF biomarkers for both clinical trials and routine clinical diagnosis of AD. PMID:24795085

  7. Update on the core and developing cerebrospinal fluid biomarkers for Alzheimer disease

    PubMed Central

    Babi?, Mirjana; Švob Štrac, Dubravka; Mück-Šeler, Dorotea; Pivac, Nela; Stani?, Gabrijela; Hof, Patrick R.; Šimi?, Goran

    2014-01-01

    Alzheimer disease (AD) is a complex neurodegenerative disorder, whose prevalence will dramatically rise by 2050. Despite numerous clinical trials investigating this disease, there is still no effective treatment. Many trials showed negative or inconclusive results, possibly because they recruited only patients with severe disease, who had not undergone disease-modifying therapies in preclinical stages of AD before severe degeneration occurred. Detection of AD in asymptomatic at risk individuals (and a few presymptomatic individuals who carry an autosomal dominant monogenic AD mutation) remains impractical in many of clinical situations and is possible only with reliable biomarkers. In addition to early diagnosis of AD, biomarkers should serve for monitoring disease progression and response to therapy. To date, the most promising biomarkers are cerebrospinal fluid (CSF) and neuroimaging biomarkers. Core CSF biomarkers (amyloid ?1-42, total tau, and phosphorylated tau) showed a high diagnostic accuracy but were still unreliable for preclinical detection of AD. Hence, there is an urgent need for detection and validation of novel CSF biomarkers that would enable early diagnosis of AD in asymptomatic individuals. This article reviews recent research advances on biomarkers for AD, focusing mainly on the CSF biomarkers. In addition to core CSF biomarkers, the potential usefulness of novel CSF biomarkers is discussed. PMID:25165049

  8. Unilateral Endoscopic Approach for Repair of Frontal Sinus Cerebrospinal Fluid Leak

    PubMed Central

    Roehm, Corrie E.; Brown, Seth M.

    2011-01-01

    Cerebrospinal fluid (CSF) leak closure remains one of the most difficult surgeries for skull base surgeons, particularly with frontal sinus involvement. Technological advances in endoscopic surgery increasingly allow for less morbid approaches to the frontal sinus. We describe a series of patients who underwent endoscopic frontal sinus CSF leak repair utilizing a unilateral approach, to evaluate the utility and outcomes of this method. We performed a retrospective review of four cases in tertiary care centers. Participants included patients with CSF leak involving the frontal sinus. Main outcome measures included cessation of CSF leak and frontal sinus patency. Three patients were closed on the first surgical attempt; one with a communicating hydrocephalus required a revision procedure. Leak etiologies included prior craniotomy for frontal sinus mucopyocele, spontaneous meningoencephalocele, erosion due to mucormycosis, and prior endoscopic sinus surgery. The frontal sinus remained patent in three of four patients. No patients have evidence of a leak at a minimum of 1 year after surgery. The repair of frontal sinus CSF leaks is possible in specific cases with an endoscopic unilateral approach in leaks with multiple etiologies. Surgeons should consider this approach when selecting the appropriate procedure for repair of frontal sinus CSF leaks. PMID:22451816

  9. Effects of Blood Contamination and the Rostro-Caudal Gradient on the Human Cerebrospinal Fluid Proteome

    PubMed Central

    Aasebø, Elise; Opsahl, Jill Anette; Bjørlykke, Yngvild; Myhr, Kjell-Morten; Kroksveen, Ann Cathrine; Berven, Frode S.

    2014-01-01

    Over the last years there has been an increased focus on the importance of knowing the effect of pre-analytical influence on the proteomes under study, particularly in the field of biomarker discovery. We present three proteomics studies examining the effect of blood contamination and the rostro-caudal gradient (RCG) on the cerebrospinal fluid (CSF) proteome, in addition to plasma/CSF protein ratios. The studies showed that the central nervous system (CNS) derived proteins appeared to be unaffected by the RCG, while the plasma-derived proteins showed an increase in concentration towards the lumbar area. This implies that the concentration of the plasma-derived proteins in CSF will vary depending on the volume of CSF that is collected. In the CSF samples spiked with blood, 262 of 814 quantified proteins showed an abundance increase of more than 1.5 fold, while 403 proteins had a fold change of less than 1.2 and appeared to be unaffected by blood contamination. Proteins with a high plasma/CSF ratio appeared to give the largest effect on the CSF proteome upon blood contamination. The results give important background information on how factors like blood contamination, RCG and blood-CNS-barrier influences the CSF proteome. This information is particularly important in the field of biomarker discovery, but also for routine clinical measurements. The data from the blood contamination and RCG discovery studies have been deposited to the ProteomeXchange with identifier PXD000401. PMID:24599184

  10. Changes in Cerebrospinal Fluid Biomarkers in Human Herpesvirus-6-Associated Acute Encephalopathy/Febrile Seizures

    PubMed Central

    Tanuma, Naoyuki; Miyata, Rie; Nakajima, Keisuke; Okumura, Akihisa; Kubota, Masaya; Hamano, Shin-ichiro; Hayashi, Masaharu

    2014-01-01

    To determine the involvement of oxidative stress in the pathogenesis of acute encephalopathy associated with human herpesvirus-6 (HHV-6) infection, we measured the levels of oxidative stress markers 8-hydroxy-2?-deoxyguanosine (8-OHdG) and hexanoyl-lysine adduct (HEL), tau protein, and cytokines in cerebrospinal fluid (CSF) obtained from patients with HHV-6-associated acute encephalopathy (HHV-6 encephalopathy) (n = 16) and complex febrile seizures associated with HHV-6 (HHV-6 complex FS) (n = 10). We also examined changes in CSF-8OHdG and CSF-HEL levels in patients with HHV-6 encephalopathy before and after treatment with edaravone, a free radical scavenger. CSF-8-OHdG levels in HHV-6 encephalopathy and HHV-6 complex FS were significantly higher than in control subjects. In contrast, CSF-HEL levels showed no significant difference between groups. The levels of total tau protein in HHV-6 encephalopathy were significantly higher than in control subjects. In six patients with HHV-6 infection (5 encephalopathy and 1 febrile seizure), the CSF-8-OHdG levels of five patients decreased after edaravone treatment. Our results suggest that oxidative DNA damage is involved in acute encephalopathy associated with HHV-6 infection. PMID:25294958

  11. Sequential analysis of biomarkers in cerebrospinal fluid and serum during invasive meningococcal disease.

    PubMed

    Beran, O; Lawrence, D A; Andersen, N; Dzupova, O; Kalmusova, J; Musilek, M; Holub, M

    2009-07-01

    The aim of the present study was to determine the profile of different inflammatory molecules in serum and cerebrospinal fluid (CSF) during invasive meningococcal disease (IMD). Their relationship with IMD severity was also assessed. A cohort of 12 patients with IMD was investigated. Paired serum and CSF samples were obtained at the time of diagnostic and follow-up lumbar puncture and were examined using Luminex analysis. IMD severity correlated with serum interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1 ra) on admission. Furthermore, the CSF levels of IL-1 beta, IL-1 ra, IL-6, IL-8, macrophage inflammatory protein-1 beta (MIP-1 beta), and monocyte chemoattractant protein-1 (MCP-1) were significantly higher than their respective serum levels. The strongest correlations were found between serum concentrations of IL-1 beta and IL-1 ra, IL-6, IL-8, and MIP-1 beta, whereas the strongest correlations in CSF were found between endotoxin and IL-8, IL-17, MIP-1 beta, and MCP-1. As was expected, the concentrations of inflammatory molecules in both serum and CSF significantly decreased after antibiotic treatment. With regard to kinetics, a severe course of IMD correlated positively with rapid declines of CSF IL-6 and cortisol levels. Sequential multiple analyses revealed patterns of inflammatory responses that were associated with the severity of IMD, as well as with the compartmentalization and kinetics of the immune reaction. PMID:19205764

  12. Identification of a New Cyclovirus in Cerebrospinal Fluid of Patients with Acute Central Nervous System Infections

    PubMed Central

    Tan, Le Van; van Doorn, H. Rogier; Nghia, Ho Dang Trung; Chau, Tran Thi Hong; Tu, Le Thi Phuong; de Vries, Michel; Canuti, Marta; Deijs, Martin; Jebbink, Maarten F.; Baker, Stephen; Bryant, Juliet E.; Tham, Nguyen Thi; BKrong, Nguyen Thi Thuy Chinh; Boni, Maciej F.; Loi, Tran Quoc; Phuong, Le Thi; Verhoeven, Joost T. P.; Crusat, Martin; Jeeninga, Rienk E.; Schultsz, Constance; Chau, Nguyen Van Vinh; Hien, Tran Tinh; van der Hoek, Lia; Farrar, Jeremy; de Jong, Menno D.

    2013-01-01

    ABSTRACT Acute central nervous system (CNS) infections cause substantial morbidity and mortality, but the etiology remains unknown in a large proportion of cases. We identified and characterized the full genome of a novel cyclovirus (tentatively named cyclovirus-Vietnam [CyCV-VN]) in cerebrospinal fluid (CSF) specimens of two Vietnamese patients with CNS infections of unknown etiology. CyCV-VN was subsequently detected in 4% of 642 CSF specimens from Vietnamese patients with suspected CNS infections and none of 122 CSFs from patients with noninfectious neurological disorders. Detection rates were similar in patients with CNS infections of unknown etiology and those in whom other pathogens were detected. A similar detection rate in feces from healthy children suggested food-borne or orofecal transmission routes, while high detection rates in feces from pigs and poultry (average, 58%) suggested the existence of animal reservoirs for such transmission. Further research is needed to address the epidemiology and pathogenicity of this novel, potentially zoonotic virus. PMID:23781068

  13. Analysis of brain nuclei accessible to ghrelin present in the cerebrospinal fluid.

    PubMed

    Cabral, A; Fernandez, G; Perello, M

    2013-12-01

    Ghrelin is a stomach-derived peptide hormone that acts in the brain to regulate many important physiological functions. Ghrelin receptor, named the growth hormone secretagogue receptor (GHSR), is present in many brain areas with or without obvious direct access to ghrelin circulating in the bloodstream. Ghrelin is also present in the cerebrospinal fluid (CSF) but the brain targets of CSF ghrelin are unclear. Here, we studied which brain areas are accessible to ghrelin present in the CSF. For this purpose, we centrally injected mice with fluorescein-labeled ghrelin (F-ghrelin) peptide tracer and then systematically mapped the distribution of F-ghrelin signal through the brain. Our results indicated that centrally injected F-ghrelin labels neurons in most of the brain areas where GHSR is present. Also, we detected F-ghrelin uptake in the ependymal cells of both wild-type and GHSR-null mice. We conclude that CSF ghrelin is able to reach most of brain areas expressing GHSR. Also, we propose that the accessibility of CSF ghrelin to the brain parenchyma occurs through the ependymal cells in a GHSR-independent manner. PMID:24042041

  14. Role of cerebrospinal fluid-contacting nucleus in sodium sensing and sodium appetite.

    PubMed

    Xing, Dan; Wu, Yuehong; Li, Guangling; Song, Siyuan; Liu, Yuepeng; Liu, He; Wang, Xing; Fei, Yan; Zhang, Chao; Li, Ying; Zhang, Licai

    2015-08-01

    The brainstem plays an important role in controlling sodium and water homeostasis. It is a major regulatory site for autonomic and motor functions. Moreover, it integrates cerebrospinal fluid (CSF) signals with neuronal and hormonal signals. Evidence suggests that the CSF-contacting nucleus (CSF-CN) transmits and integrates CSF signals, but, the definitive role of CSF-CN in sodium homeostasis is poorly understood. In this study, we used c-Fos as a marker of neuronal activity and causing colocalization of Nax channel and 5-HT. This proved that CSF-CN played a role in sensing the increase of CSF sodium level. Then, we determined the role of the CSF-contacting nucleus in increasing the sodium appetite of rats. So, we performed targeted lesion of the CSF-contacting nucleus in the brainstem using the cholera toxin subunit B-saporin (CB-SAP), a cytotoxin coupled to cholera toxin subunit B. The lesion of the CSF-CN showed decreased and degenerative neurons, while sodium appetite have increased and Fos immunocytochemistry detected neuronal activity in the lateral parabrachial nucleus (LPBN), but not in the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT). These results indicate that the CSF-CN plays an important role in sensing CSF sodium level and satiating sodium appetite by influencing the LPBN but not SFO and OVLT. The Nax channel and 5-HT might be the molecular mechanisms through which contribute to sodium homeostasis. PMID:25911266

  15. Diagnosis of acute leukemia in cerebrospinal fluid (CSF-acute leukemia).

    PubMed

    Crespo-Solis, Erick; López-Karpovitch, Xavier; Higuera, Jesús; Vega-Ramos, Beatriz

    2012-10-01

    Cerebrospinal fluid-acute leukemia (CSF-acute leukemia) is a frequent and serious complication in patients with acute leukemia. One of the major problems of this complication is the diagnosis process itself. CSF cytology is currently considered the gold standard for establishing the diagnosis, a technique which presents various processing limitations, seriously impacting the predictive values. In the last 11 years, studies of CSF flow cytometry analysis done in patients with acute leukemia have demonstrated superiority in comparison with CSF cytology. Although comparative studies between these two techniques have been reported since 2001, no new consensus or formal changes to the gold standard have been established for the CSF acute leukemia diagnosis. The evidence suggests that positive flow cytometry cases, considered as indeterminate cases, will behave like disease in the central nervous system (CNS). Nevertheless, we think there are some variables and considerations that must be first evaluated under research protocols before CNS relapse can be established with only one positive flow cytometry analysis in the setting of indeterminate CSF samples. This paper proposes a diagnostic algorithm and complementary strategies. PMID:22639108

  16. Effect of clomipramine on monoamine metabolites in the cerebrospinal fluid of behaviorally normal dogs.

    PubMed Central

    Hewson, C J; Luescher, U A; Parent, J M; Ball, R O

    2000-01-01

    The tricyclic antidepressant, clomipramine, is an effective treatment for canine compulsive disorder (canine CD). This disorder is a clinical syndrome of abnormal conflict behaviors and its pathophysiology is unknown. However, because clomipramine is an effective treatment, information about the drug's neurochemical effect could enhance the understanding of canine CD. The following experiment used 6 behaviorally normal dogs to assess the effect of clomipramine (3 mg/kg, q24h, PO) on the central turnover of 3 monoamines (serotonin, dopamine, and norepinephrine) as measured by the concentrations of their respective metabolites in cerebrospinal fluid (CSF). In a randomized, placebo-controlled, AB-BA crossover experiment, cisternal CSF was taken after 1, 2, 4, and 6 wk on each treatment. No effect of clomipramine was detected. This contrasts with human studies that have suggested that clomipramine affects the concentrations of monoamine metabolites in lumbar CSF. However, those papers do not address methodological assumptions, such as (i) metabolites in CSF originate only from the brain, and (ii) concentrations of metabolites in cisternal/lumbar CSF reflect the concentrations in local areas of the brain. Notwithstanding the small sample size, our results suggest that more localized sampling techniques (e.g. microdialysis) are needed when examining the effect of drugs on central monoamine metabolites. Clomipramine's efficacy for canine CD indicates the need for neurobiological research and, to our knowledge, our study is the first of its kind in dogs. The resulting data are preliminary but they can inform optimal neurobiological studies of canine CD. PMID:10805252

  17. Inductively coupled microfluidic pressure meter for in vivo monitoring of cerebrospinal fluid shunt function.

    PubMed

    Song, S-H; Gillies, G T; Begley, M R; Utz, M; Broaddus, W C

    2012-04-01

    A microfluidic pressure sensor with inductively coupled, wireless readout capability has been developed for integration into cerebrospinal fluid shunt valve implants. The sensor consists of a deformable PDMS film that is bonded over a microfluidic reservoir, forming a fluidic capacitor. Deflection of the capacitor membrane is detected remotely through a shift in the resonance frequency of a micro-fabricated LC circuit. Sensors were fabricated by a combination of conventional MEMS technologies and rapid soft lithography. A direct pattern transfer technique was used to pattern the deformable PDMS film with a metal coating for the capacitive readout. The mechanical response of the fluidic capacitor was characterized by measuring the deflection of the PDMS film using an extrinsic Fabry-Perot interferometer (EFPI), and wireless sensing was demonstrated by the shift in resonance frequency of the sensor via an inductively coupled antenna. The sensor transduces pressure into a change in resonant frequency with sensitivity >?3.4?ppm Pa?¹ and responsivity 4.6?kHz Pa?¹, over a dynamic range of 0~3 kPa. PMID:22316101

  18. Measurement of cerebrospinal fluid formation and absorption by ventriculo-cisternal perfusion: what is really measured?

    PubMed

    Oreškovi?, Darko; Klarica, Marijan

    2014-08-28

    The generally accepted hypothesis on cerebrospinal fluid (CSF) hydrodynamics suggests that CSF is actively formed mainly by the choroid plexuses, circulates unidirectionally along the brain ventricles and subarachnoid space, and is passively absorbed mainly into the dural venous sinuses. CSF formation rate (Vf) has been extensively studied using the ventriculo-cisternal perfusion technique and the results have been used as the key evidence confirming the mentioned hypothesis. This technique and the equation for Vf calculation are based on the assumption that the dilution of the indicator substance is a consequence of the newly formed CSF, ie, that a higher CSF formation rate will result in a higher degree of dilution. However, it has been experimentally shown that the indicator substance dilution inside the CSF system does not occur because of a "newly formed" CSF, but as consequence of a number of other factors (departure of substances into the surrounding tissue, flowing around the collecting cannula into the cortical and spinal subarachnoid space, departure into the contralateral ventricle, etc). This technique allows "calculation" of the CSF formation even in dead animals, in an in vitro model, and in any other part of the CSF system outside the ventricles that is being perfused. Therefore, this method is indirect and any dilution of the indicator substance in the perfusate caused by other reasons would result in questionable and often contradictory conclusions regarding CSF formation rates. PMID:25165046

  19. Partial characterization of a novel endogenous opioid in human cerebrospinal fluid

    SciTech Connect

    Miller, B.E.; Lipman, J.J.; Byrne, W.L.

    1987-12-07

    Human cerebrospinal fluid (CSF) contains many uncharacterized endogenous opioids, in addition to the known enkephalins, endorphins, and dynorphins. These opioids may be separated by gel filtration chromatography and identified by radioreceptor assay for opioid activity. One region of the chromatographic elution profile, designated Peak B has previously been shown to be related to the pain status of chronic pain patients. The authors now report that human Peak B isolated from the CSF of pain-free elective surgery patients is present at a typical concentration equivalent in activity to 1.4 pmol of morphine sulfate per ml of CSF measured by radioreceptor assay. At a dose of 0.06 and 0.12 pmol morphine sulfate equivalents of CSF (MSE), injected into the cerebroventricular system of the mouse, Peak B produced an antinociceptive effect, the intensity and duration of which was dose-dependent and which was antagonized by naloxone. The mouse vas deferens (MVD) preparation was inhibited by Peak B in a manner that was sensitive to antagonism by naloxone only at low (< 1.0 ..mu..M) but not at higher (>6.0 ..mu..M) concentrations of the antagonist. Peak B activity in the MVD assay was unaffected by treatment with trypsin or ..cap alpha..-chymotrypsin. 32 references, 4 figures, 1 table.

  20. Detection of Human Herpesvirus 6 in Cerebrospinal Fluid of Children With Possible Encephalitis

    PubMed Central

    Yavarian, Jila; Gavvami, Nastaran; Mamishi, Setareh

    2013-01-01

    Background: Encephalitis is swelling and inflammation of brain, usually due to viral infection. Viral encephalitis symptoms could be fever, headache, altered level of consciousness, and seizures. Objectives: The aim of this study was detection of human herpesvirus-6 (HHV-6) DNA in cerebrospinal fluid (CSF) of patients with symptoms of possible acute encephalitis and without typical signs or symptoms of roseola infantum, using real-time polymerase chain reaction (PCR). Patients and Methods: We studied children two years old or younger, admitted to the pediatric emergency ward with encephalitis-like symptoms. Our evaluation included detection of HHV-6 in CSF of these patients. After DNA extraction, real-time PCR was performed with primers and a probe specific for the U22 open reading frame of both HHV-6A and B. Results: From a total of 114 patients, HHV-6 was detected in 10 (8.8%), 90% of which were boys with mean age 7.7 months and median of 7.5 months. No significant differences were found in clinical presentations and laboratory findings between the patients positive and negative for HHV-6. All the children had complete recovery without neurological deficit or death. Conclusions: According to this research and prevalence of HHV-6 in children, evaluation of CSF (detecting the HHV-6 DNA by PCR) is recommended in patients younger than 13 months with possible encephalitis. PMID:25485059

  1. Analysis of Brain Nuclei Accessible to Ghrelin Present in the Cerebrospinal Fluid

    PubMed Central

    Cabral, Agustina; Fernandez, Gimena; Perello, Mario

    2013-01-01

    Ghrelin is a stomach-derived peptide hormone that acts in the brain to regulate many important physiological functions. Ghrelin receptor, named the growth hormone secretagogue receptor (GHSR), is present in many brain areas with or without obvious direct access to ghrelin circulating in the bloodstream. Ghrelin is also present in the cerebrospinal fluid (CSF) but the brain targets of CSF ghrelin are unclear. Here, we studied which brain areas are accessible to ghrelin present in the CSF. For this purpose, we centrally injected mice with fluorescein-labeled ghrelin (F-ghrelin) peptide tracer and then systematically mapped the distribution of F-ghrelin signal trough the brain. Our results indicated that centrally injected F-ghrelin labels neurons in most of the brain areas where GHSR is present. Also, we detected F-ghrelin uptake in the ependymal cells of both wild type and GHSR-null mice. We conclude that CSF ghrelin is able to reach most of brain areas expressing GHSR. Also, we propose that the accessibility of CSF ghrelin to the brain parenchyma occurs through the ependymal cells in a GHSR-independent manner. PMID:24042041

  2. Evidence for fungal infection in cerebrospinal fluid and brain tissue from patients with amyotrophic lateral sclerosis.

    PubMed

    Alonso, Ruth; Pisa, Diana; Marina, Ana Isabel; Morato, Esperanza; Rábano, Alberto; Rodal, Izaskun; Carrasco, Luis

    2015-01-01

    Among neurogenerative diseases, amyotrophic lateral sclerosis (ALS) is a fatal illness characterized by a progressive motor neuron dysfunction in the motor cortex, brainstem and spinal cord. ALS is the most common form of motor neuron disease; yet, to date, the exact etiology of ALS remains unknown. In the present work, we have explored the possibility of fungal infection in cerebrospinal fluid (CSF) and in brain tissue from ALS patients. Fungal antigens, as well as DNA from several fungi, were detected in CSF from ALS patients. Additionally, examination of brain sections from the frontal cortex of ALS patients revealed the existence of immunopositive fungal antigens comprising punctate bodies in the cytoplasm of some neurons. Fungal DNA was also detected in brain tissue using PCR analysis, uncovering the presence of several fungal species. Finally, proteomic analyses of brain tissue demonstrated the occurrence of several fungal peptides. Collectively, our observations provide compelling evidence of fungal infection in the ALS patients analyzed, suggesting that this infection may play a part in the etiology of the disease or may constitute a risk factor for these patients. PMID:25892962

  3. Cerebrospinal fluid biomarkers of neurovascular dysfunction in mild dementia and Alzheimer's disease.

    PubMed

    Sweeney, Melanie D; Sagare, Abhay P; Zlokovic, Berislav V

    2015-07-01

    Alzheimer's disease (AD) is the most common form of age-related dementias. In addition to genetics, environment, and lifestyle, growing evidence supports vascular contributions to dementias including dementia because of AD. Alzheimer's disease affects multiple cell types within the neurovascular unit (NVU), including brain vascular cells (endothelial cells, pericytes, and vascular smooth muscle cells), glial cells (astrocytes and microglia), and neurons. Thus, identifying and integrating biomarkers of the NVU cell-specific responses and injury with established AD biomarkers, amyloid-? (A?) and tau, has a potential to contribute to better understanding of the disease process in dementias including AD. Here, we discuss the existing literature on cerebrospinal fluid biomarkers of the NVU cell-specific responses during early stages of dementia and AD. We suggest that the clinical usefulness of established AD biomarkers, A? and tau, could be further improved by developing an algorithm that will incorporate biomarkers of the NVU cell-specific responses and injury. Such biomarker algorithm could aid in early detection and intervention as well as identify novel treatment targets to delay disease onset, slow progression, and/or prevent AD. PMID:25899298

  4. Increased Cerebrospinal Fluid Production as a Possible Mechanism Underlying Caffeine's Protective Effect against Alzheimer's Disease

    PubMed Central

    Wostyn, Peter; Van Dam, Debby; Audenaert, Kurt; De Deyn, Peter Paul

    2011-01-01

    Alzheimer's disease (AD), the most common type of dementia among older people, is characterized by the accumulation of ?-amyloid (A?) senile plaques and neurofibrillary tangles composed of hyperphosphorylated tau in the brain. Despite major advances in understanding the molecular etiology of the disease, progress in the clinical treatment of AD patients has been extremely limited. Therefore, new and more effective therapeutic approaches are needed. Accumulating evidence from human and animal studies suggests that the long-term consumption of caffeine, the most commonly used psychoactive drug in the world, may be protective against AD. The mechanisms underlying the suggested beneficial effect of caffeine against AD remain to be elucidated. In recent studies, several potential neuroprotective effects of caffeine have been proposed. Interestingly, a recent study in rats showed that the long-term consumption of caffeine increased cerebrospinal fluid (CSF) production, associated with the increased expression of Na+-K+ ATPase and increased cerebral blood flow. Compromised function of the choroid plexus and defective CSF production and turnover, with diminished clearance of A?, may be one mechanism implicated in the pathogenesis of late-onset AD. If reduced CSF turnover is a risk factor for AD, then therapeutic strategies to improve CSF flow are reasonable. In this paper, we hypothesize that long-term caffeine consumption could exert protective effects against AD at least in part by facilitating CSF production, turnover, and clearance. Further, we propose a preclinical experimental design allowing evaluation of this hypothesis. PMID:21660211

  5. Drug Transporters on Arachnoid Barrier Cells Contribute to the Blood–Cerebrospinal Fluid Barrier

    PubMed Central

    Yasuda, Kazuto; Cline, Cynthia; Vogel, Peter; Onciu, Mihaela; Fatima, Soghra; Sorrentino, Brian P.; Thirumaran, Ranjit K.; Ekins, Sean; Urade, Yoshihiro; Fujimori, Ko

    2013-01-01

    The subarachnoid space, where cerebrospinal fluid (CSF) flows over the brain and spinal cord, is lined on one side by arachnoid barrier (AB) cells that form part of the blood-CSF barrier. However, despite the fact that drugs are administered into the CSF and CSF drug concentrations are used as a surrogate for brain drug concentration following systemic drug administration, the tight-junctioned AB cells have never been examined for whether they express drug transporters that would influence CSF and central nervous system drug disposition. Hence, we characterized drug transporter expression and function in AB cells. Immunohistochemical analysis showed P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) in mouse AB cells but not other meningeal tissue. The Gene Expression Nervous System Atlas (GENSAT) database and the Allen Mouse Brain Atlas confirmed these observations. Microarray analysis of mouse and human arachnoidal tissue revealed expression of many drug transporters and some drug-metabolizing enzymes. Immortalized mouse AB cells express functional P-gp on the apical (dura-facing) membrane and BCRP on both apical and basal (CSF-facing) membranes. Thus, like blood-brain barrier cells and choroid plexus cells, AB cells highly express drug transport proteins and likely contribute to the blood-CSF drug permeation barrier. PMID:23298861

  6. Oxytocin-messages via the cerebrospinal fluid: behavioral effects; a review.

    PubMed

    Veening, Jan G; de Jong, Trynke; Barendregt, Henk P

    2010-09-01

    The cerebrospinal fluid (CSF) usually is considered as a protective 'nutrient and waste control' system for the brain. Recent findings suggest, however, that the composition of CSF is actively controlled and may play an influential role in the changes in brain activity, underlying different behavioral states. In the present review, we present an overview of available data concerning the release of oxytocin into the CSF, the location of the oxytocin-receptive brain areas and the behavioral effects of intracerebroventricular oxytocin. About 80% of the oxytocin-receptive areas are located close to the ventricular or subarachnoid CSF, including the hypothalamic 'Behavior Control Column' (L.W.Swanson, 2003). As a conclusion we suggest that 'CSF-oxytocin' contributes considerably to the non-synaptic communication processes involved in hypothalamic-, brainstem- and olfactory brain areas and behavioral states and that the flowing CSF is used as a 'broadcasting system' to send coordinated messages to a wide variety of nearby and distant brain areas. PMID:20493198

  7. Identification of a Biomarker in Cerebrospinal Fluid for Neuronopathic Forms of Gaucher Disease

    PubMed Central

    Zigdon, Hila; Savidor, Alon; Levin, Yishai; Meshcheriakova, Anna; Schiffmann, Raphael; Futerman, Anthony H.

    2015-01-01

    Gaucher disease, a recessive inherited metabolic disorder caused by defects in the gene encoding glucosylceramidase (GlcCerase), can be divided into three subtypes according to the appearance of symptoms associated with central nervous system involvement. We now identify a protein, glycoprotein non-metastatic B (GPNMB), that acts as an authentic marker of brain pathology in neurological forms of Gaucher disease. Using three independent techniques, including quantitative global proteomic analysis of cerebrospinal fluid (CSF) in samples from Gaucher disease patients that display neurological symptoms, we demonstrate a correlation between the severity of symptoms and GPNMB levels. Moreover, GPNMB levels in the CSF correlate with disease severity in a mouse model of Gaucher disease. GPNMB was also elevated in brain samples from patients with type 2 and 3 Gaucher disease. Our data suggest that GPNMB can be used as a marker to quantify neuropathology in Gaucher disease patients and as a marker of treatment efficacy once suitable treatments towards the neurological symptoms of Gaucher disease become available. PMID:25775479

  8. Cerebrospinal fluid from a 7-month-old dog with seizure-like episodes.

    PubMed

    Amude, Alexandre M; Alfieri, Amauri A; Balarin, Mara R S; dos Reis, Antônio C F; Alfieri, Alice F

    2006-03-01

    A 7-month-old dog was presented to the Veterinary Teaching Hospital of the Universidade Estadual de Londrina, Paraná, Brazil with a 1-week history of seizure-like activity and compulsive walking. Neurological deficits included seizures, nystagmus, absence of a menace reaction, depressed postural reactions, spastic tetraparesis, opisthotonos, and spasticity of the thoracic limbs. Cerebrospinal fluid (CSF) evaluation showed severe lymphocytic pleocytosis (554 cells/microL, with 70% lymphocytes) and a protein concentration of 17 mg/dL. The histopathologic findings in cerebrum, cerebellum, and brainstem obtained at necropsy were compatible with acute encephalomyelitis caused by canine distemper virus (CDV). Using reverse transcription-polymerase chain reaction (RT-PCR), CDV RNA was detected in both CSF and fragments of fresh brain tissue. The results indicated that CDV was the agent responsible for the clinical and laboratory presentation. Severe pleocytosis with lymphocyte predominance is an unusual finding in canine distemper and must be differentiated from granulomatous meningoencephalitis. RT-PCR on CSF is a useful, fast, and specific method to diagnose CDV infection in dogs. PMID:16511803

  9. Cerebrospinal fluid biomarkers for differentiation of frontotemporal lobar degeneration from Alzheimer's disease

    PubMed Central

    Irwin, David J.; Trojanowski, John Q.; Grossman, Murray

    2013-01-01

    Accurate ante mortem diagnosis in frontotemporal lobar degeneration (FTLD) is crucial to the development and implementation of etiology-based therapies. Several neurodegenerative disease-associated proteins, including the major protein constituents of inclusions in Alzheimer's disease (AD) associated with amyloid-beta (A?1?42) plaque and tau neurofibrillary tangle pathology, can be measured in cerebrospinal fluid (CSF) for diagnostic applications. Comparative studies using autopsy-confirmed samples suggest that CSF total-tau (t-tau) and A?1?42 levels can accurately distinguish FTLD from AD, with a high t-tau to A?1?42 ratio diagnostic of AD; however, there is also an urgent need for FTLD-specific biomarkers. These analytes will require validation in large autopsy-confirmed cohorts and face challenges of standardization of within- and between-laboratory sources of error. In addition, CSF biomarkers with prognostic utility and longitudinal study of CSF biomarker levels over the course of disease are also needed. Current goals in the field include identification of analytes that are easily and reliably measured and can be used alone or in a multi-modal approach to provide an accurate prediction of underlying neuropathology for use in clinical trials of disease modifying treatments in FTLD. To achieve these goals it will be of the utmost importance to view neurodegenerative disease, including FTLD, as a clinicopathological entity, rather than exclusively a clinical syndrome. PMID:23440936

  10. Cerebrospinal fluid biomarkers and cerebral atrophy in distinct clinical variants of probable Alzheimer's disease.

    PubMed

    Ossenkoppele, Rik; Mattsson, Niklas; Teunissen, Charlotte E; Barkhof, Frederik; Pijnenburg, Yolande; Scheltens, Philip; van der Flier, Wiesje M; Rabinovici, Gil D

    2015-08-01

    Different clinical variants of probable Alzheimer's disease (AD) share underlying plaques and tangles but show distinct atrophy patterns. We included 52 posterior cortical atrophy, 29 logopenic variant primary progressive aphasia, 53 early-onset and 42 late-onset AD patients, selected for abnormal cerebrospinal fluid (CSF)-amyloid-beta42, with CSF and magnetic resonance imaging data available. Bootstrapping revealed no differences in the prevalence of abnormal CSF total-tau and phosphorylated-tau between probable AD variants (range total-tau: 84.9%-92.3%, phosphorylated-tau: 79.2%-93.1%, p > 0.05). Voxelwise linear regressions showed various relationships between lower CSF-A?42 and syndrome-specific atrophy, involving precuneus, posterior cingulate, and medial temporal lobe in early-onset AD, occipital cortex and middle temporal gyrus in posterior cortical atrophy; anterior cingulate, insular cortex and precentral gyrus (left > right) in logopenic variant primary progressive aphasia; and medial temporal lobe, thalamus, and temporal pole in late-onset AD (all at p < 0.001 uncorrected). In contrast, CSF-tau was not related to gray matter atrophy in any group. Our findings suggest that lower CSF-amyloid-beta42 - and not increased total-tau and phosphorylated-tau - relates to reduced gray matter volumes, mostly in regions that are typically atrophied in distinct clinical variants of probable AD. PMID:25990306

  11. Cerebrospinal fluid-iophendylate contrast on gradient-echo MR images.

    PubMed

    Jack, C R; Gehring, D G; Ehman, R L; Felmlee, J P

    1988-11-01

    The effect on the signal intensities of cerebrospinal fluid (CSF) and iophendylate (Pantopaque) and on CSF-iophendylate contrast was studied in vitro with a small-nutation-angle (alpha) gradient refocused magnetic resonance (MR) imaging technique (GRASS) as alpha, repetition time (TR), and echo time (TE) were varied. CSF signal intensity was consistently greater than that of iophendylate. Therefore, retained intraspinal iophendylate may be considered in the differential diagnosis of focal areas of low signal intensity at the periphery of the spinal canal on GRASS images. At constant TE and TR, an increase in alpha from 6 degrees to 45 degrees increased the signal intensities of CSF and iophendylate but decreased CSF-iophendylate contrast. At constant alpha and TR, an increase in TE from 13 to 28 msec decreased the signal intensities of CSF and iophendylate but increased contrast. At constant alpha and TE, an increase in TR from 50 to 400 msec increased the signal intensities of CSF and iophendylate, as well as contrast. Clinical examples of the contrast behavior of retained intraspinal iophendylate on both spin-echo and GRASS images corroborate the experimental findings. Retained intraspinal iophendylate may mimic the appearance of intra-or extra-dural lesions, magnetic susceptibility artifact, and flow on gradient-echo MR images of the spine. PMID:3175007

  12. A New Technique for Collection of Cerebrospinal Fluid in Rat Pups

    PubMed Central

    Rodríguez-Fanjul, Javier; Fernández-Feijóo, Cristina Durán; Camprubí, Marta Camprubí

    2015-01-01

    BACKGROUND Neuroprotective strategies to prevent or decrease brain injury in hypoxic ischemic newborns are one of the main research lines in neonatology. Animal models have been used to assess the efficiency of new therapeutic strategies. Brain damage biomarkers in cerebrospinal fluid (CSF) are frequently used to evaluate the outcome at the bedside. Despite the importance of this approach in clinical practice, there are many difficulties in using it in small animals. The aim of this paper was to describe a new technique for collecting CSF in rat pups. Furthermore the reference values of S100? protein levels, commonly used in common clinical practice, were analyzed in animals between 7 to 12 days. METHODS 42 Wistar rat pups aged 7 to 12 days were used. CSF was obtained by direct puncture of the cisterna magna with a 24-gauge needle. S100? protein levels were determined with enzyme-linked immunosorbent assay (ELISA). RESULTS CSF was successfully obtained in 96% of the cases, with an average amount of 21.28 ?l (5–40 ?l). Normal values for S100? were described. HI animals presented higher S100? values than controls. CONCLUSIONS A simple, reproducible technique for CSF collection in rat pups has been described. This new method will allow study of brain injury biomarkers in newborn hypoxic ischemic animal models. PMID:26056488

  13. Cerebrospinal fluid-derived Semaphorin3B orients neuroepithelial cell divisions in the apicobasal axis.

    PubMed

    Arbeille, Elise; Reynaud, Florie; Sanyas, Isabelle; Bozon, Muriel; Kindbeiter, Karine; Causeret, Frédéric; Pierani, Alessandra; Falk, Julien; Moret, Frédéric; Castellani, Valérie

    2015-01-01

    The spatial orientation of cell divisions is fundamental for tissue architecture and homeostasis. Here we analysed neuroepithelial progenitors in the developing mouse spinal cord to determine whether extracellular signals orient the mitotic spindle. We report that Semaphorin3B (Sema3B) released from the floor plate and the nascent choroid plexus in the cerebrospinal fluid (CSF) controls progenitor division orientation. Delivery of exogenous Sema3B to neural progenitors after neural tube opening in living embryos promotes planar orientation of their division. Preventing progenitor access to cues present in the CSF by genetically engineered canal obstruction affects the proportion of planar and oblique divisions. Sema3B knockout phenocopies the loss of progenitor access to the CSF. Sema3B binds to the apical surface of mitotic progenitors and exerts its effect via Neuropilin receptors, GSK3 activation and subsequent inhibition of the microtubule stabilizer CRMP2. Thus, extrinsic control mediated by the Semaphorin signalling orients progenitor divisions in neurogenic zones. PMID:25721514

  14. Cerebrospinal fluid B cells from Multiple Sclerosis patients are subject to normal germinal center selection

    PubMed Central

    Harp, Christopher; Lee, Jane; Lambracht-Washington, Doris; Cameron, Elizabeth; Olsen, Gregory; Frohman, Elliot; Racke, Michael; Monson, Nancy

    2007-01-01

    Previous findings from our laboratory demonstrated that some clonally expanded cerebrospinal fluid (CSF) B cells from MS patients exhibit diminished mutation targeting patterns in comparison to typical B cells selected in the context of germinal centers (GCs). In order to determine whether the overall CSF B cell repertoires adhered to mutation patterns typical of GC-selected B cells, we analyzed the immunoglobulin repertoires from CSF B cells of 8 MS patients for mutation characteristics typical of GC-derived B cells. Mutation targeting was preserved. Thus, clonal expansion of some CSF B cells may occur independently of GC, but the CSF B cell pool is governed by typical GC selection. Interestingly, the heavy chain CDR3’s of CSF B cells from MS patients had a net acidic charge, similar to GC-derived B cells, but a tendency towards longer CDR3’s, consistent with autoreactive B cells. How these findings may support current hypotheses regarding the origin of CSF B cells is discussed. PMID:17169437

  15. Spontaneous cerebrospinal fluid leakage through fistulas at the clivus repaired with endoscopic endonasal approach

    PubMed Central

    Hayashi, Yasuhiko; Iwato, Masayuki; Kita, Daisuke; Fukui, Issei

    2015-01-01

    Background: Causes of cerebrospinal fluid (CSF) leakage are primarily traumatic or iatrogenic in origin. In contrast, spontaneous CSF leakage is somewhat rare, and detection of the fistula can be challenging. Meningitis associated with CSF leakage can be life threatening. It is therefore critical to surgically repair the fistula once the underlying cause has been accurately identified. Spontaneous CSF leakage located at the clivus is an extremely rare condition. Case Description: We present the case of a 38-year-old male with sudden-onset headache and subsequent disturbances of consciousness. The patient was diagnosed with severe meningitis caused by CSF leakage through fistulas at the clivus, which were clearly identified on dynamic imaging using high-resolution computed tomography (CT) with intrathecal injection of contrast medium. After the meningitis was resolved, successful endoscopic repair of the CSF fistula with autologous materials was performed. There has been no recurrence of meningitis for 5 years. Conclusion: Spontaneous CSF leakage at the clivus is an extremely rare condition. High-resolution CT cisternogram could accurately detect CSF leakage through the clivus. A transnasal endoscopic approach was a useful and reliable method of repairing the fistula at the clivus.

  16. Glioblastoma multiforme with epithelial differentiation: A potential diagnostic pitfall in cerebrospinal fluid cytology.

    PubMed

    Gill, Simpal K; Padmanabhan, Vijayalakshmi; Hickey, William F; Marotti, Jonathan D

    2015-08-01

    Cerebrospinal fluid (CSF) cytology provides valuable diagnostic and prognostic information for diseases of the central nervous system (CNS) and remains the gold standard for the detection of neoplastic meningitis. Metastatic involvement of the CSF by non-CNS neoplasms far surpasses that of primary brain tumors, although conventional glioblastoma multiforme (GBM) can occasionally be identified in the CSF. GBM with epithelial differentiation is an uncommon variant that may contain features such as adenoid structures, signet ring cells, or squamous metaplasia. Herein, we present a case of GBM with epithelial differentiation to highlight a potential diagnostic pitfall in CSF cytology. A 55-year-old man presented with neurological symptoms and a 6.4 cm left temporal lobe cystic mass. Primary resection revealed GBM with focal epithelial differentiation confirmed by cytokeratin, epithelial membrane antigen, and glial fibrillary acidic protein immunohistochemical studies. Four months following primary resection, the patient developed severe headache for which a lumbar puncture with CSF cytologic evaluation was performed. The cytospin preparation showed numerous malignant epithelioid cells with high nuclear-cytoplasmic ratio and prominent cytoplasmic vacuoles resembling metastatic carcinoma. However, the lesional cells were cytomorphologically identical to the epithelial component present in the patient's recently diagnosed GBM. This case illustrates the potential for GBM with epithelial differentiation to closely mimic metastatic carcinoma from a non-CNS site in CSF cytology, which expands the differential diagnosis and emphasizes the necessity of clinical correlation. Diagn. Cytopathol. 2015;43:638-641. © 2015 Wiley Periodicals, Inc. PMID:25913842

  17. Role of Cerebrospinal Fluid Biomarkers in Clinical Trials for Alzheimer's Disease Modifying Therapies

    PubMed Central

    Ryoo, Na-Young; Shin, Dong Wun; Trojanowski, John Q

    2014-01-01

    Until now, a disease-modifying therapy (DMT) that has an ability to slow or arrest Alzheimer's disease (AD) progression has not been developed, and all clinical trials involving AD patients enrolled by clinical assessment alone also have not been successful. Given the growing consensus that the DMT is likely to require treatment initiation well before full-blown dementia emerges, the early detection of AD will provide opportunities to successfully identify new drugs that slow the course of AD pathology. Recent advances in early detection of AD and prediction of progression of the disease using various biomarkers, including cerebrospinal fluid (CSF) A?1-42, total tau and p-tau181 levels, and imagining biomarkers, are now being actively integrated into the designs of AD clinical trials. In terms of therapeutic mechanisms, monitoring these markers may be helpful for go/no-go decision making as well as surrogate markers for disease severity or progression. Furthermore, CSF biomarkers can be used as a tool to enrich patients for clinical trials with prospect of increasing statistical power and reducing costs in drug development. However, the standardization of technical aspects of analysis of these biomarkers is an essential prerequisite to the clinical uses. To accomplish this, global efforts are underway to standardize CSF biomarker measurements and a quality control program supported by the Alzheimer's Association. The current review summarizes therapeutic targets of developing drugs in AD pathophysiology, and provides the most recent advances in the PMID:25598657

  18. High cerebrospinal fluid levels of interleukin-10 attained by AAV in dogs.

    PubMed

    Pleticha, J; Malkmus, S A; Heilmann, L F; Veesart, S L; Rezek, R; Xu, Q; Yaksh, T L; Beutler, A S

    2015-02-01

    Intrathecal (IT) gene transfer using adeno-associated virus (AAV) may be clinically promising as a treatment for chronic pain if it can produce sufficiently high levels of a transgene product in the cerebrospinal fluid (CSF). Although this strategy was developed in rodents, no studies investigating CSF levels of an analgesic or antiallodynic protein delivered by IT AAV have been performed in large animals. Interleukin-10 (IL-10) is an antiallodynic cytokine for which target therapeutic levels have been established in rats. The present study tested IT AAV8 encoding either human IL-10 (hIL-10) or enhanced green fluorescent protein (EGFP) in a dog model of IT drug delivery. AAV8/hIL-10 at a dose of 3.5 × 10(12) genome copies induced high hIL-10 levels in the CSF, exceeding the target concentration previously found to be antiallodynic in rodents by >1000-fold. AAV8/EGFP targeted the primary sensory and motor neurons and the meninges. hIL-10, a xenogeneic protein in dogs, induced anti-hIL-10 antibodies detectable in the CSF and serum of dogs. The high hIL-10 levels demonstrate the efficacy of AAV for delivery of secreted transgenes into the IT space of large animals, suggesting a strong case for further development toward clinical testing. PMID:25354684

  19. Approach to Cerebrospinal Fluid (CSF) Biomarker Discovery and Evaluation in HIV Infection

    SciTech Connect

    Price, Richard W.; Peterson, Julia; Fuchs, Dietmar; Angel, Thomas E.; Zetterberg, Henrik; Hagberg, Lars; Spudich, Serena S.; Smith, Richard D.; Jacobs, Jon M.; Brown, Joseph N.; Gisslen, Magnus

    2013-12-13

    Central nervous system (CNS) infection is a nearly universal facet of systemic HIV infection that varies in character and neurological consequences. While clinical staging and neuropsychological test performance have been helpful in evaluating patients, cerebrospinal fluid (CSF) biomarkers present a valuable and objective approach to more accurate diagnosis, assessment of treatment effects and understanding of evolving pathobiology. We review some lessons from our recent experience with CSF biomarker studies. We have used two approaches to biomarker analysis: targeted, hypothesis-driven and non-targeted exploratory discovery methods. We illustrate the first with data from a cross-sectional study of defined subject groups across the spectrum of systemic and CNS disease progression and the second with a longitudinal study of the CSF proteome in subjects initiating antiretroviral treatment. Both approaches can be useful and, indeed, complementary. The first is helpful in assessing known or hypothesized biomarkers while the second can identify novel biomarkers and point to broad interactions in pathogenesis. Common to both is the need for well-defined samples and subjects that span a spectrum of biological activity and biomarker concentrations. Previouslydefined guide biomarkers of CNS infection, inflammation and neural injury are useful in categorizing samples for analysis and providing critical biological context for biomarker discovery studies. CSF biomarkers represent an underutilized but valuable approach to understanding the interactions of HIV and the CNS and to more objective diagnosis and assessment of disease activity. Both hypothesis-based and discovery methods can be useful in advancing the definition and use of these biomarkers.

  20. Diagnostic value of cerebrospinal fluid antibodies in herpes simplex virus encephalitis.

    PubMed

    Koskiniemi, M L; Vaheri, A

    1982-03-01

    Antibodies to different viruses and bacteria were measured in the cerebrospinal fluid (CSF) of six patients with herpes simplex virus encephalitis proven by brain biopsy and in five others with a presumptive diagnosis. Antibodies to herpes simplex virus but not to other organisms appeared in the CSF of all patients after the first weeks of the illness. Herpes simplex virus antibodies were not found in control CSF. The antibodies persisted in the CSF and the serum/CSF antibody ratio remained altered, 32:1 to less than 1:1, in all cases during the follow-up to 29 months or until death. The CSF albumin level was normal and the IgG index (formula: see text) elevated in four proven and three presumptive cases indicating a local antibody production; in four patients the findings were inconsistent. These results suggest that prolonged antigen stimulation is present in the central nervous system after acute herpes simplex encephalitis and that serological measurements combined with immunoglobulin and albumin determinations may provide a tentative but not definite diagnosis in some cases after the acute phase of encephalitis together with a method for follow-up of patients. PMID:6283030

  1. [Radioimmunofixation: a new technic for characterizing immunoglobulins in unconcentrated cerebrospinal fluid. Preliminary results].

    PubMed

    Chazot, G; Lasne, Y; Benzerara, O; Confavreux, C; Schott, B

    1980-01-01

    The restriction of heterogenicity of immunoglobulins G (IgG), or oligoclonal distribution, in the cerebrospinal fluid (CSF) can be observed after electrophoresis or electrofocalization, the IgG nature of each oligoclonal band being confirmed by subsequent immuno-electrophoresis. Using immunofixation, the oligoclonal bands can be visualized and characterized simultaneously, but requires previous concentration of the CSF, which is a source of error. The technique of radioimmunofixation, here described, allows the study of IgG with 20 microliters of non-concentrated CSF. It demonstrates that the oligoclonal characteristic is present in normal CSF and is a more quantitative than qualitative feature. Preliminary results show that the method can be applied to the study of all CSF proteins. By using a viral antigen labelled with I-125, for example, it should be possible to reveal and visualize the antibody activity of each oligoclonal band and to determine whether the quantitative increase in an oligoclonal band corresponds to a definite antigenic stimulation. PMID:7209242

  2. Volume transmission of beta-endorphin via the cerebrospinal fluid; a review

    PubMed Central

    2012-01-01

    There is increasing evidence that non-synaptic communication by volume transmission in the flowing CSF plays an important role in neural mechanisms, especially for extending the duration of behavioral effects. In the present review, we explore the mechanisms involved in the behavioral and physiological effects of ?-endorphin (?-END), especially those involving the cerebrospinal fluid (CSF), as a message transport system to reach distant brain areas. The major source of ?-END are the pro-opio-melano-cortin (POMC) neurons, located in the arcuate hypothalamic nucleus (ARH), bordering the 3rd ventricle. In addition, numerous varicose ?-END-immunoreactive fibers are situated close to the ventricular surfaces. In the present paper we surveyed the evidence that volume transmission via the CSF can be considered as an option for messages to reach remote brain areas. Some of the points discussed in the present review are: release mechanisms of ?-END, independence of peripheral versus central levels, central ?-END migration over considerable distances, behavioral effects of ?-END depend on location of ventricular administration, and abundance of mu and delta opioid receptors in the periventricular regions of the brain. PMID:22883598

  3. Isobaric tagging-based selection and quantitation of cerebrospinal fluid tryptic peptides with reporter calibration curves.

    PubMed

    Dayon, Loïc; Turck, Natacha; Kienle, Stefan; Schulz-Knappe, Peter; Hochstrasser, Denis F; Scherl, Alexander; Sanchez, Jean-Charles

    2010-02-01

    In the past few years, mass spectrometry (MS) has emerged as an efficient tool for the multiplexed peptide and protein concentration determination by isotope dilution. Despite the growing use of isobaric tagging to perform relative quantitation for the discovery of potential biomarkers in biological fluids, no real application has so far been presented for their absolute quantitation. Isobaric tandem mass tags (TMTs) were used herein for the selection and quantitation of tryptic peptides derived from brain damage related proteins in cerebrospinal fluid (CSF). Proteotypic tryptic peptide analogues were synthesized, prepared in four reference amounts, differentially labeled with four isobaric TMTs with reporter-ions at m/z = 128.1, 129.1, 130.1, and 131.1, and mixed with CSF sample previously labeled with TMT 126.1. Off-gel electrophoresis (OGE) was used as first-dimension separation of the pooled sample. The resulting fractions were analyzed with reversed-phase liquid chromatography (RP-LC) tandem mass spectrometry (MS/MS), using tandem time-of-flight (TOF/TOF) and hybrid linear ion trap-orbitrap (LTQ-OT) instruments. Under collision-induced dissociation (CID) or higher-energy C-trap dissociation (HCD), the release of the reporter fragments from the TMT-labeled peptide standards provided an internal calibration curve to assess the concentration of these peptides in the CSF. This tool also allowed identifying selectively these peptides in CSF as only the targeted peptides showed specific fragmentation pattern in the TMT reporter-ion zone of the tandem mass spectra. Assays for the concentration measurements of peptides from PARK7, GSTP1, NDKA, and S100B proteins in CSF were further characterized using this novel, efficient, and straightforward approach. PMID:20058875

  4. Prion-seeding activity in cerebrospinal fluid of deer with chronic wasting disease.

    PubMed

    Haley, Nicholas J; Van de Motter, Alexandra; Carver, Scott; Henderson, Davin; Davenport, Kristen; Seelig, Davis M; Mathiason, Candace; Hoover, Edward

    2013-01-01

    Transmissible spongiform encephalopathies (TSEs), or prion diseases, are a uniformly fatal family of neurodegenerative diseases in mammals that includes chronic wasting disease (CWD) of cervids. The early and ante-mortem identification of TSE-infected individuals using conventional western blotting or immunohistochemistry (IHC) has proven difficult, as the levels of infectious prions in readily obtainable samples, including blood and bodily fluids, are typically beyond the limits of detection. The development of amplification-based seeding assays has been instrumental in the detection of low levels of infectious prions in clinical samples. In the present study, we evaluated the cerebrospinal fluid (CSF) of CWD-exposed (n=44) and naïve (n=4) deer (n=48 total) for CWD prions (PrP(d)) using two amplification assays: serial protein misfolding cyclic amplification with polytetrafluoroethylene beads (sPMCAb) and real-time quaking induced conversion (RT-QuIC) employing a truncated Syrian hamster recombinant protein substrate. Samples were evaluated blindly in parallel with appropriate positive and negative controls. Results from amplification assays were compared to one another and to obex immunohistochemistry, and were correlated to available clinical histories including CWD inoculum source (e.g. saliva, blood), genotype, survival period, and duration of clinical signs. We found that both sPMCAb and RT-QuIC were capable of amplifying CWD prions from cervid CSF, and results correlated well with one another. Prion seeding activity in either assay was observed in approximately 50% of deer with PrP(d) detected by IHC in the obex region of the brain. Important predictors of amplification included duration of clinical signs and time of first tonsil biopsy positive results, and ultimately the levels of PrP(d) identified in the obex by IHC. Based on our findings, we expect that both sPMCAb and RT-QuIC may prove to be useful detection assays for the detection of prions in CSF. PMID:24282599

  5. Ciliogenesis and cerebrospinal fluid flow in the developing Xenopus brain are regulated by foxj1

    PubMed Central

    2013-01-01

    Background Circulation of cerebrospinal fluid (CSF) through the ventricular system is driven by motile cilia on ependymal cells of the brain. Disturbed ciliary motility induces the formation of hydrocephalus, a pathological accumulation of CSF resulting in ventricle dilatation and increased intracranial pressure. The mechanism by which loss of motile cilia causes hydrocephalus has not been elucidated. The aim of this study was: (1) to provide a detailed account of the development of ciliation in the brain of the African clawed frog Xenopus laevis; and (2) to analyze the relevance of ependymal cilia motility for CSF circulation and brain ventricle morphogenesis in Xenopus. Methods Gene expression analysis of foxj1, the bona fide marker for motile cilia, was used to identify potentially ciliated regions in the developing central nervous system (CNS) of the tadpole. Scanning electron microscopy (SEM) was used to reveal the distribution of mono- and multiciliated cells during successive stages of brain morphogenesis, which was functionally assessed by bead injection and video microscopy of ventricular CSF flow. An antisense morpholino oligonucleotide (MO)-mediated gene knock-down that targeted foxj1 in the CNS was applied to assess the role of motile cilia in the ventricles. Results RNA transcripts of foxj1 in the CNS were found from neurula stages onwards. Following neural tube closure, foxj1 expression was seen in distinct ventricular regions such as the zona limitans intrathalamica (ZLI), subcommissural organ (SCO), floor plate, choroid plexus (CP), and rhombomere boundaries. In all areas, expression of foxj1 preceded the outgrowth of monocilia and the subsequent switch to multiciliated ependymal cells. Cilia were absent in foxj1 morphants, causing impaired CSF flow and fourth ventricle hydrocephalus in tadpole-stage embryos. Conclusions Motile ependymal cilia are important organelles in the Xenopus CNS, as they are essential for the circulation of CSF and maintenance of homeostatic fluid pressure. The Xenopus CNS ventricles might serve as a novel model system for the analysis of human ciliary genes whose deficiency cause hydrocephalus. PMID:24229449

  6. Effect of Embryonic Cerebrospinal Fluid on Proliferation and Differentiation of Neuroprogenitor Cells

    PubMed Central

    Yari, Siamak; Parivar, Kazem; Nabiuni, Mohammad; Keramatipour, Mohammad

    2013-01-01

    Objective: Embryonic cerebrospinal fluid (e-CSF) has an important role in development of embryonic and adult brain. Proteomic analysis suggests that this fluid has many morphogenes and cytokines that alter in time and space throughout embryonic life. The aim of this study was to evaluate the developmental effect of embryonic CSF on proliferation and differentiation of neuroprogenitor cells in different gestational age. Materials and Methods: In this In this experimental study, we examined the role of e- CSF on proliferation and differentiation of neuroprogenitor cells using neurosphere culture method. Neurospheres size analysis and MTT assay were used to assess cell proliferation after four days in vitro. Glial differentiation study was carried out by immunocytochemistry. Neurospheres size and percentage of glial fibrialy acidic protein (GFAP) positive cells were measured by image analyzer (image J). The data were analyzed by one-way ANOVA, followed by the Tukey’s post hoc test. Data were expressed as mean ± SEM, and differences were considered significant when p<0.05, 0.01 and 0.001. Results: Viability and proliferation of neuro progenitor cells in cultures conditioned with E16 CSF and E18 CSF were significantly increased compare to control group. A dramatic decrease in percentage of GFAP-positive cells was found following the application of CSF from E16 and E18 embryos, but not E20 CSF. Conclusion: Our data suggest that, e-CSF altered proliferation and differentiation of neuro progenitor cells in age dependent manner. E16 and E18 CSF enhanced proliferation and viability of neuro progenitor cells, and inhibited differentiation to glial fate in comparison with control group. PMID:23700558

  7. Integration of the subarachnoid space and lymphatics: Is it time to embrace a new concept of cerebrospinal fluid absorption?

    PubMed Central

    Koh, Lena; Zakharov, Andrei; Johnston, Miles

    2005-01-01

    In most tissues and organs, the lymphatic circulation is responsible for the removal of interstitial protein and fluid but the parenchyma of the brain and spinal cord is devoid of lymphatic vessels. On the other hand, the literature is filled with qualitative and quantitative evidence supporting a lymphatic function in cerebrospinal fluid (CSF) absorption. The experimental data seems to warrant a re-examination of CSF dynamics and consideration of a new conceptual foundation on which to base our understanding of disorders of the CSF system. The objective of this paper is to review the key studies pertaining to the role of the lymphatic system in CSF absorption. PMID:16174293

  8. Amyloid-beta peptide and oligomers in the brain and cerebrospinal fluid of aged canines.

    PubMed

    Head, Elizabeth; Pop, Viorela; Sarsoza, Floyd; Kayed, Rakez; Beckett, Tina L; Studzinski, Christa M; Tomic, Jennifer L; Glabe, Charles G; Murphy, M Paul

    2010-01-01

    The study of Alzheimer's disease (AD) pathogenesis requires the use of animal models that develop some amount of amyloid pathology in the brain. Aged canines (beagles) naturally accumulate human-type amyloid-beta peptide (Abeta) and develop parallel declines in cognitive function. However, the type and quantity of biochemically extracted Abeta in brain and cerebrospinal fluid (CSF), its link to aging, and similarity to human aging has not been examined systematically. Thirty beagles, aged 4.5-15.7 years, were studied. Abeta40 and Abeta42 were measured in CSF by ELISA, and from SDS and formic acid extracted prefrontal cortex. A sample of the contralateral hemisphere, used to assess immunohistochemical amyloid load, was used for comparison. In the brain, increases in Abeta42 were detected at a younger age, prior to increases in Abeta40, and were correlated with an increased amyloid load. In the CSF, Abeta42 decreased with age while Abeta40 levels remained constant. The CSF Abeta42/40 ratio was also a good predictor of the amount of Abeta in the brain. The amount of soluble oligomers in CSF was inversely related to brain extractable Abeta, whereas oligomers in the brain were correlated with SDS soluble Abeta42. These findings indicate that the Abeta in the brain of the aged canine exhibits patterns that mirror Abeta deposited in the human brain. These parallels support the idea that the aged canine is a useful intermediate between transgenic mice and humans for studying the development of amyloid pathology and is a potentially useful model for the refinement of therapeutic interventions. PMID:20164551

  9. Cerebrospinal fluid biomarkers for Alzheimer disease and subcortical axonal damage in 5,542 clinical samples

    PubMed Central

    2013-01-01

    Introduction The neuronal loss in Alzheimer disease (AD) has been described to affect grey matter in the cerebral cortex. However, in the elderly, AD pathology is likely to occur together with subcortical axonal degeneration on the basis of cerebrovascular disease. Therefore, we hypothesized that biomarkers for AD and subcortical axonal degeneration would correlate in patients undergoing testing for dementia biomarkers, particularly in older age groups. Methods We performed correlation and cluster analyses of cerebrospinal fluid (CSF) biomarker data from 5,542 CSF samples analyzed in our routine clinical neurochemistry laboratory in 2010 through 2012 for the established CSF AD biomarkers total tau (T-tau), phosphorylated-tau (P-tau), amyloid ?1-42 (A?42), and for neurofilament light (NFL), which is a protein expressed in large-caliber myelinated axons, the CSF levels of which correlate with subcortical axonal injury. Results A?42, T-tau, and P-tau correlated with NFL. By cluster analysis, we found a bimodal data distribution in which a group with a low A?42/P-tau ratio (suggesting AD pathology) had high levels of NFL. High levels of NFL also correlated with the presence of an AD biomarker pattern defined by A?42/P-tau and T-tau. Only 29% of those with an AD biomarker signature had normal NFL levels. Age was a possible confounding factor for the associations between NFL and established AD biomarkers, but in a logistic regression analysis, both age and NFL independently predicted the AD biomarker pattern. Conclusions The association between an AD-like signature using the established biomarkers A?42, T-tau, and P-tau with increased levels of NFL provides in vivo evidence of an association between AD and subcortical axonal degeneration in this uniquely large dataset of CSF samples tested for dementia biomarkers. PMID:24479774

  10. Cerebrospinal fluid estrone in pseudotumor cerebri: a change in cerebral steroid hormone metabolism?

    PubMed

    Toscano, V; Sancesario, G; Bianchi, P; Cicardi, C; Casilli, D; Giacomini, P

    1991-02-01

    Estrogen and androgen hormones were studied in the plasma and cerebrospinal fluid (CSF) of five patients affected by pseudotumor cerebri (PTC). Six men and six women without cerebral or endocrine diseases were selected as controls. Androstenedione (A), testosterone (T), 17-hydroxyprogesterone (17OH-P), E1 and E2 were measured in plasma and CSF in baseline conditions and following 1 month prednisone therapy (2 mg/die, per os) using RIA following chromatographic separation on celite microcolumns. Men and women affected by PTC show increased CSF E1 levels and marked decreased CSF A levels, with respect to controls. In plasma, on the contrary, normal values of these parameters were observed in PTC. In normal subjects A/E1 ratio shows the same values in plasma and CSF, suggesting for the two hormones analogous feasibility to cross the blood brain barrier. In PTC patients A/E1 ratio is comparable to controls in plasma, but lower in CSF as a result of decreased A and increased E1 contents. The CSF imbalance between A and E1 attenuates but does not disappear after treatment. No correlation is found between pressure levels and steroid pattern both in baseline condition or after one month of treatment. In conclusion, our results demonstrate that PTC is not only associated with increased CSF E1 levels, as previously suggested, but, above all, with decreased CSF A levels and this hormonal impairement seems to be confined to the CSF compartment and not observed in plasma. These data do not lead to any definitive conclusion about the role of altered CSF estrogen and androgen levels in PTC pathogenesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2061573

  11. The Streptococcus suis transcriptional landscape reveals adaptation mechanisms in pig blood and cerebrospinal fluid

    PubMed Central

    Wu, Zongfu; Wu, Chunyan; Shao, Jing; Zhu, Zhenzhen; Wang, Weixue; Zhang, Wenwei; Tang, Min; Pei, Na; Fan, Hongjie; Li, Jiguang; Yao, Huochun; Gu, Hongwei; Xu, Xun; Lu, Chengping

    2014-01-01

    Streptococcus suis (SS) is an important pathogen of pigs, and it is also recognized as a zoonotic agent for humans. SS infection may result in septicemia or meningitis in the host. However, little is known about genes that contribute to the virulence process and survival within host blood or cerebrospinal fluid (CSF). Small RNAs (sRNA) have emerged as key regulators of virulence in several bacteria, but they have not been investigated in SS. Here, using a differential RNA-sequencing approach and RNAs from SS strain P1/7 grown in rich medium, pig blood, or CSF, we present the SS genome-wide map of 793 transcriptional start sites and 370 operons. In addition to identifying 29 sRNAs, we show that five sRNA deletion mutants attenuate SS virulence in a zebrafish infection model. Homology searches revealed that 10 sRNAs were predicted to be present in other pathogenic Streptococcus species. Compared with wild-type strain P1/7, sRNAs rss03, rss05, and rss06 deletion mutants were significantly more sensitive to killing by pig blood. It is possible that rss06 contributes to SS virulence by indirectly activating expression of SSU0308, a virulence gene encoding a zinc-binding lipoprotein. In blood, genes involved in the synthesis of capsular polysaccharide (CPS) and subversion of host defenses were up-regulated. In contrast, in CSF, genes for CPS synthesis were down-regulated. Our study is the first analysis of SS sRNAs involved in virulence and has both improved our understanding of SS pathogenesis and increased the number of sRNAs known to play definitive roles in bacterial virulence. PMID:24759092

  12. Development of a cerebrospinal fluid lateral reservoir model in rhesus monkeys (Macaca mulatta).

    PubMed

    Lester McCully, Cynthia M; Bacher, John; MacAllister, Rhonda P; Steffen-Smith, Emilie A; Saleem, Kadharbatcha; Thomas, Marvin L; Cruz, Rafael; Warren, Katherine E

    2015-02-01

    Rapid, serial, and humane collection of cerebrospinal fluid (CSF) in nonhuman primates (NHP) is an essential element of numerous research studies and is currently accomplished via two different models. The CSF reservoir model (FR) combines a catheter in the 4th ventricle with a flexible silastic reservoir to permit circulating CSF flow. The CSF lateral port model (LP) consists of a lateral ventricular catheter and an IV port that provides static access to CSF and volume restrictions on sample collection. The FR model is associated with an intensive, prolonged recovery and frequent postsurgical hydrocephalus and nonpatency, whereas the LP model is associated with an easier recovery. To maximize the advantages of both systems, we developed the CSF lateral reservoir model (LR), which combines the beneficial features of the 2 previous models but avoids their limitations by using a reservoir for circulating CSF flow combined with catheter placement in the lateral ventricle. Nine adult male rhesus monkeys were utilized in this study. Pre-surgical MRI was performed to determine the coordinates of the lateral ventricle and location of choroid plexus (CP). The coordinates were determined to avoid the CP and major blood vessels. The predetermined coordinates were 100% accurate, according to MRI validation. The LR system functioned successfully in 67% of cases for 221 d, and 44% remain functional at 426 to 510 d postoperatively. Compared with established models, our LR model markedly reduced postoperative complications and recovery time. Development of the LR model was successful in rhesus macaques and is a useful alternative to the FR and LP methods of CSF collection from nonhuman primates. PMID:25730761

  13. Identification of extracellular miRNA in human cerebrospinal fluid by next-generation sequencing

    PubMed Central

    Burgos, Kasandra Lovette; Javaherian, Ashkan; Bomprezzi, Roberto; Ghaffari, Layla; Rhodes, Susan; Courtright, Amanda; Tembe, Waibhav; Kim, Seungchan; Metpally, Raghu; Van Keuren-Jensen, Kendall

    2013-01-01

    There has been a growing interest in using next-generation sequencing (NGS) to profile extracellular small RNAs from the blood and cerebrospinal fluid (CSF) of patients with neurological diseases, CNS tumors, or traumatic brain injury for biomarker discovery. Small sample volumes and samples with low RNA abundance create challenges for downstream small RNA sequencing assays. Plasma, serum, and CSF contain low amounts of total RNA, of which small RNAs make up a fraction. The purpose of this study was to maximize RNA isolation from RNA-limited samples and apply these methods to profile the miRNA in human CSF by small RNA deep sequencing. We systematically tested RNA isolation efficiency using ten commercially available kits and compared their performance on human plasma samples. We used RiboGreen to quantify total RNA yield and custom TaqMan assays to determine the efficiency of small RNA isolation for each of the kits. We significantly increased the recovery of small RNA by repeating the aqueous extraction during the phenol-chloroform purification in the top performing kits. We subsequently used the methods with the highest small RNA yield to purify RNA from CSF and serum samples from the same individual. We then prepared small RNA sequencing libraries using Illumina’s TruSeq sample preparation kit and sequenced the samples on the HiSeq 2000. Not surprisingly, we found that the miRNA expression profile of CSF is substantially different from that of serum. To our knowledge, this is the first time that the small RNA fraction from CSF has been profiled using next-generation sequencing. PMID:23525801

  14. Identification of human cerebrospinal fluid proteins and their distribution in an in vitro microdialysis sampling system.

    PubMed

    Wetterhall, Magnus; Bergquist, Jonas; Hillered, Lars; Hjort, Klas; Dahlin, Andreas P

    2014-06-16

    A qualitative study is presented on how proteins from a complex biological sample are distributed in a microdialysis sample system. A comparison between proteins identified in the human ventricular cerebrospinal fluid (CSF) sample, the collected dialysate and the proteins adsorbed onto the membrane was conducted. The microdialysis experiment was performed in vitro at 37°C for the duration of 24h. Thereafter, the membranes were removed from the catheter and the adsorbed proteins were tryptically digested using the on-surface enzymatic digestion (oSED) protocol. The CSF samples and the dialysates were digested using a standard in-solution trypsin digestion protocol. In the final phase, the samples were analysed using nano-liquid chromatography in combination with tandem mass spectrometry. In the four sample compartments analysed (CSF start, Membrane, Dialysate, CSF end) a total of 134 different proteins were found. However, most of the identified proteins (n=87) were uniquely found in one sample compartment only. Common CSF proteins such as albumin, apolipoproteins and cystatin C together with plasma proteins such as hemoglobin and fibrinogen were among the 11 proteins that were found in all samples. These proteins are present in high concentrations in CSF, which means that they effectively block out the detection signal of less abundant proteins. Therefore, only 25% of the proteins adsorbed onto the membrane were detected in the CSF compared with the dialysate that shared 44% of its proteins with the CSF. The proteins adsorbed onto the membrane were significantly more hydrophobic, had a lower instability index and more thermostable compared to the proteins in the CSF and the dialysate. The results suggest that proteins adsorbed onto the microdialysis membranes may escape detection because they are prevented from passing the membrane into the dialysate. Thus, the membrane needs to be examined after sample collection in order to better verify the protein content in the original sample. This is particularly important when searching for new protein biomarkers for neurodegenerative diseases. PMID:24361471

  15. Reduced alpha-synuclein in cerebrospinal fluid in synucleinopathies: evidence from a meta-analysis.

    PubMed

    Sako, Wataru; Murakami, Nagahisa; Izumi, Yuishin; Kaji, Ryuji

    2014-11-01

    Alpha-synuclein plays a key role in the pathology of synucleinopathies including Parkinson's disease (PD) and multiple system atrophy (MSA). However, whether alpha-synuclein level in cerebrospinal fluid (CSF) could distinguish synucleinopathies from progressive supranuclear palsy (PSP) is still a contentious issue. A comprehensive literature search yielded nine eligible studies. We expressed the between-group difference of the concentration of alpha-synuclein in CSF as the standardized mean difference. The proportion of variation attributable to heterogeneity was computed and expressed as I(2) . Nine studies involved 537 controls, 843 PD, 130 MSA, and 98 PSP patients. The overall effect of PD on alpha-synuclein in CSF was significantly different from normal control or disease control (standardized mean difference = -0.67, P < 0.00001). These studies were heterogeneous (I(2) = 40%). Alpha-synuclein in CSF in MSA was significantly reduced relative to controls with heterogeneous studies (standardized mean difference = -0.75, P < 0.0001; I(2) = 62%). In contrast, no significant difference of alpha-synuclein in CSF was observed between PSP and controls with heterogeneous studies (standardized mean difference = -0.28, P = 0.13; I(2) = 53%). Alpha-synuclein in CSF was significantly reduced in synucleinopathies compared with PSP ("PD vs. PSP": standardized mean difference = -0.38, P = 0.001; "MSA vs. PSP": standardized mean difference = -0.66, P < 0.00001). The included studies were homogeneous (I(2) = 0%). Our study showed that alpha-synuclein levels in CSF in synucleinopathies was significantly lower than in PSP. This finding provides insights into the pathophysiological difference between synucleinopathies and PSP as well as possibility of development of a tool for differential diagnosis between MSA and PSP using enzyme-linked immunosorbent assay (ELISA) and similar methods. PMID:25258345

  16. Effects of Lowering Cerebrospinal Fluid Pressure on the Shape of the Peripapillary Retina in Intracranial Hypertension

    PubMed Central

    Sibony, Patrick; Kupersmith, Mark J.; Honkanen, Robert; Rohlf, F. James; Torab-Parhiz, Ali

    2014-01-01

    Purpose. To analyze the deformations of the peripapillary retinal pigment epithelium–basement membrane (ppRPE/BM) layer in response to procedures that lower intracranial pressure (ICP). Second, to demonstrate how shape changes may complement the mean retinal nerve fiber layer (RNFL) thickness as a measure of intracranial hypertension (ICH) and papilledema. Methods. We used geometric morphometrics on spectral-domain optical coherence tomography images to analyze shape change of the ppRPE/BM layer after several interventions that lower cerebrospinal fluid (CSF) pressure. We also evaluated the effects of pressure-lowering interventions on both the anterior–posterior displacement of ppRPE/BM and the mean RNFL thickness. Forty-one patients with ICH and papilledema were studied before and after lumbar puncture (20), CSF shunt (9), and medical treatment of idiopathic ICH (23). We also compared the shape of 30 normal subjects to 23 patients whose papilledema resolved after medical treatment. Results. The ppRPE/BM-layer in ICH and papilledema is characterized by an asymmetric anterior deformation that moves posteriorly and becomes more V-shaped after each pressure-lowering intervention. The differences were statistically significant for all three groups. These shape changes also occur in patients with ongoing ICH who have secondary optic atrophy (without papilledema). Posterior displacement at the margin of the ppRPE/BM layer correlated strongly with overall shape changes. Conclusions. The subsurface contour of the ppRPE/BM layer is a dynamic property that changes with CSF pressure-lowering interventions. It can supplement the RNFL thickness as an indirect gauge of ICP and is particularly helpful in patients with secondary optic atrophy. Direct measurements of displacement at the basement membrane opening may serve as a more convenient office-based surrogate for shape analysis. PMID:25406288

  17. Intracranial pressure pulse waveform correlates with aqueductal cerebrospinal fluid stroke volume

    PubMed Central

    Hamilton, Robert; Baldwin, Kevin; Fuller, Jennifer; Vespa, Paul; Hu, Xiao

    2012-01-01

    This study identifies a novel relationship between cerebrospinal fluid (CSF) stroke volume through the cerebral aqueduct and the characteristic peaks of the intracranial pulse (ICP) waveform. ICP waveform analysis has become much more advanced in recent years; however, clinical practice remains restricted to mean ICP, mainly due to the lack of physiological understanding of the ICP waveform. Therefore, the present study set out to shed some light on the physiological meaning of ICP morphological metrics derived by the morphological clustering and analysis of continuous intracranial pulse (MOCAIP) algorithm by investigating their relationships with a well defined physiological variable, i.e., the stroke volume of CSF through the cerebral aqueduct. Seven patients received both overnight ICP monitoring along with a phase-contrast MRI (PC-MRI) of the cerebral aqueduct to quantify aqueductal stroke volume (ASV). Waveform morphological analysis of the ICP signal was performed by the MOCAIP algorithm. Following extraction of morphological metrics from the ICP signal, nine temporal ICP metrics and two amplitude-based metrics were compared with the ASV via Spearman's rank correlation. Of the nine temporal metrics correlated with the ASV, only the width of the P2 region (ICP-Wi2) reached significance. Furthermore, both ICP pulse pressure amplitude and mean ICP did not reach significance. In this study, we showed the width of the second peak (ICP-Wi2) of an ICP pulse wave is positively related to the volume of CSF movement through the cerebral aqueduct. This finding is an initial step in bridging the gap between ICP waveform morphology research and clinical practice. PMID:22995390

  18. Role of the cerebrospinal fluid-contacting nucleus in the descending inhibition of spinal pain transmission.

    PubMed

    Liu, He; Yan, Wei-Wei; Lu, Xiao-Xing; Zhang, Xiu-Li; Wei, Jing-Qiu; Wang, Xiao-Yu; Wang, Tiao; Wu, Tong; Cao, Jing; Shao, Cui-Jie; Zhou, Fang; Zhang, Hong-Xing; Zhang, Peng; Zang, Ting; Lu, Xian-Fu; Cao, Jun-Li; Ding, Hai-Lei; Zhang, Li-Cai

    2014-11-01

    The brainstem is well recognized as a critical site for integrating descending modulatory systems that both inhibit and facilitate pain at the level of the spinal cord. The cerebrospinal fluid-contacting nucleus (CSF-contacting nucleus) distributes and localizes in the ventral periaqueductal central gray of the brainstem. Although emerging lines of evidence suggest that the CSF-contacting nucleus may be closely linked to transduction and regulation of pain signals, the definitive role of the CSF-contacting nucleus in pain modulation remains poorly understood. In the present study, we determined the role of the CSF-contacting nucleus in rat nocifensive behaviors after persistent pain by targeted ablation of the CSF-contacting nucleus in the brainstem using the cholera toxin subunit B-saporin (CB-SAP), a cytotoxin coupled to cholera toxin subunit B. Compared with CB/SAP, CB-SAP induced complete ablation of the CSF-contacting nucleus, and the CB-SAP-treated rats showed hypersensitivity in responses to acute nociceptive stimulation, and exacerbated spontaneous nocifensive responses induced by formalin, thermal hyperalgesia and mechanical allodynia induced by plantar incision. Furthermore, immunohistochemical experiments showed that the CSF-contacting nucleus was a cluster of 5-HT-containing neurons in the brainstem, and the spinal projection of serotonergic axons originating from the CSF-contacting nucleus constituted the descending 5-HT pathway to the spinal cord. CB-SAP induced significant downregulation of 5-HT in the spinal dorsal horn, and intrathecal injection of 5-HT significantly reversed hypersensitivity in responses to acute nociceptive stimulation in the CB-SAP-treated rats. These results indicate that the CSF-contacting nucleus 5-HT pathway is an important component of the endogenous descending inhibitory system in the control of spinal nociceptive transmission. PMID:25108066

  19. Proteomic analysis of the cerebrospinal fluid of patients with restless legs syndrome/Willis-Ekbom disease

    PubMed Central

    2013-01-01

    Background Restless Legs Syndrome/Willis-Ekbom Disease (RLS/WED) is a sensorimotor disorder that causes patients to experience overwhelming and distressing sensations in the legs compelling the patient to move their legs to provide relief. The purpose of this study was to determine if biomarkers in the cerebrospinal fluid can distinguish RLS/WED patients from neurological controls. Methods We obtained CSF samples by lumbar puncture from 5 early-onset RLS/WED patients and 5 controls. We performed 2-dimensional difference in-gel electrophoresis (2D-DIGE). Proteins that were significantly altered were identified by Student’s t-test. Protein spots that were differentially expressed (p ? 0.05, Av. Ratio ? 2.0) between RLS/WED and control CSF samples were identified using MALDI-TOF-MS. Statistical analyses of the validation immunoblot assays were performed using Student’s t-test. Results In this discovery study we identified 6 candidate CSF protein markers for early-onset RLS/WED. Four proteins (Cystatin C, Lipocalin-type Prostaglandin D2 Synthase, Vitamin D binding Protein, and ?-Hemoglobin) were increased and 2 proteins (Apolipoprotein A1 and ?-1-acid Glycoprotein) were decreased in RLS/WED patients. Conclusions Our results reveal a protein profile in the RLS/WED CSF that is consistent with clinical findings of disruptive sleep, cardiovascular dysfunction and painful symptoms. Moreover, protein profiles are consistent with neuropathological findings of activation of hypoxia inducible factor (HIF) pathways and alterations in dopaminergic systems. These data indicate the CSF of RLS/WED patients may provide information relevant to biological basis for RLS/WED, treatment strategies and potential new treatment targets. PMID:23758918

  20. Features of the Sinushunt® and its influence on the cerebrospinal fluid system

    PubMed Central

    Eklund, A; Koskinen, L; Malm, J

    2004-01-01

    Objectives: A new cerebrospinal fluid (CSF) shunt system, Sinushunt®, has recently been introduced. CSF is shunted from the ventricles to the transverse sinus. The Sinushunt is not a classical differential pressure shunt; instead, it opens as soon as there is a positive pressure over the shunt and the flow is dependent on the resistance of the system, which is high compared with traditional CSF shunts. The objective of this study was to characterise the features of the Sinushunt and to evaluate its influence on the CSF system. Methods: Five brand new Sinushunts with distal catheters were tested. An automated, computerised experimental apparatus based on regulation of pressure, built into an incubator at 37 °C, was used. Opening pressure, resistance, and anti-reflux properties were determined. Results: The mean (SD) opening pressure was highly dependent on the pressure in the sinus: Popen = 1.3 (0.6) mm Hg with Psinus = 0.0 mm Hg, and Popen = 7.5 (0.6) mm Hg for Psinus = 6.5 mm Hg. The mean (SD) resistance of the shunts was 7.9 (0.3) mm Hg/ml/min and not clinically significantly affected by the sinus pressure. In one shunt there was reflux, and in another two shunts there was a very small, but similar, tendency. Conclusions: This study confirms that the resistance of the Sinushunt is comparable to the physiological values in humans. However, the optimal post-operative resistance for different hydrocephalus types is unknown, and randomised clinical trials are needed to confirm improved outcome and reduced complication rate for the Sinushunt compared with traditional low resistance ventriculoperitoneal shunts. A weakness of the anti-reflux system of the Sinushunt must be suspected and has to be further investigated. PMID:15258219

  1. Cerebrospinal fluid protein dynamic driver network: At the crossroads of brain tumorigenesis.

    PubMed

    Tan, Zhou; Liu, Rui; Zheng, Le; Hao, Shiying; Fu, Changlin; Li, Zhen; Deng, Xiaohong; Jang, Taichang; Merchant, Milton; Whitin, John C; Guo, Minyi; Cohen, Harvey J; Recht, Lawrence; Ling, Xuefeng B

    2015-07-15

    To get a better understanding of the ongoing in situ environmental changes preceding the brain tumorigenesis, we assessed cerebrospinal fluid (CSF) proteome profile changes in a glioma rat model in which brain tumor invariably developed after a single in utero exposure to the neurocarcinogen ethylnitrosourea (ENU). Computationally, the CSF proteome profile dynamics during the tumorigenesis can be modeled as non-smooth or even abrupt state changes. Such brain tumor environment transition analysis, correlating the CSF composition changes with the development of early cellular hyperplasia, can reveal the pathogenesis process at network level during a time before the image detection of the tumors. In our controlled rat model study, matched ENU- and saline-exposed rats' CSF proteomics changes were quantified at approximately 30, 60, 90, 120, 150days of age (P30, P60, P90, P120, P150). We applied our transition-based network entropy (TNE) method to compute the CSF proteome changes in the ENU rat model and test the hypothesis of the critical transition state prior to impending hyperplasia. Our analysis identified a dynamic driver network (DDN) of CSF proteins related with the emerging tumorigenesis progressing from the non-hyperplasia state. The DDN associated leading network CSF proteins can allow the early detection of such dynamics before the catastrophic shift to the clear clinical landmarks in gliomas. Future characterization of the critical transition state (P60) during the brain tumor progression may reveal the underlying pathophysiology to device novel therapeutics preventing tumor formation. More detailed method and information are accessible through our website at http://translationalmedicine.stanford.edu. PMID:25982164

  2. SCO-spondin from embryonic cerebrospinal fluid is required for neurogenesis during early brain development.

    PubMed

    Vera, A; Stanic, K; Montecinos, H; Torrejón, M; Marcellini, S; Caprile, T

    2013-01-01

    The central nervous system (CNS) develops from the neural tube, a hollow structure filled with embryonic cerebrospinal fluid (eCSF) and surrounded by neuroepithelial cells. Several lines of evidence suggest that the eCSF contains diffusible factors regulating the survival, proliferation, and differentiation of the neuroepithelium, although these factors are only beginning to be uncovered. One possible candidate as eCSF morphogenetic molecule is SCO-spondin, a large glycoprotein whose secretion by the diencephalic roof plate starts at early developmental stages. In vitro, SCO-spondin promotes neuronal survival and differentiation, but its in vivo function still remains to be elucidated. Here we performed in vivo loss of function experiments for SCO-spondin during early brain development by injecting and electroporating a specific shRNA expression vector into the neural tube of chick embryos. We show that SCO-spondin knock down induces an increase in neuroepithelial cells proliferation concomitantly with a decrease in cellular differentiation toward neuronal lineages, leading to hyperplasia in both the diencephalon and the mesencephalon. In addition, SCO-spondin is required for the correct morphogenesis of the posterior commissure and pineal gland. Because SCO-spondin is secreted by the diencephalon, we sought to corroborate the long-range function of this protein in vitro by performing gain and loss of function experiments on mesencephalic explants. We find that culture medium enriched in SCO-spondin causes an increased neurodifferentiation of explanted mesencephalic region. Conversely, inhibitory antibodies against SCO-spondin cause a reduction in neurodifferentiation and an increase of mitosis when such explants are cultured in eCSF. Our results suggest that SCO-spondin is a crucial eCSF diffusible factor regulating the balance between proliferation and differentiation of the brain neuroepithelial cells. PMID:23761733

  3. SCO-spondin from embryonic cerebrospinal fluid is required for neurogenesis during early brain development

    PubMed Central

    Vera, A.; Stanic, K.; Montecinos, H.; Torrejón, M.; Marcellini, S.; Caprile, T.

    2013-01-01

    The central nervous system (CNS) develops from the neural tube, a hollow structure filled with embryonic cerebrospinal fluid (eCSF) and surrounded by neuroepithelial cells. Several lines of evidence suggest that the eCSF contains diffusible factors regulating the survival, proliferation, and differentiation of the neuroepithelium, although these factors are only beginning to be uncovered. One possible candidate as eCSF morphogenetic molecule is SCO-spondin, a large glycoprotein whose secretion by the diencephalic roof plate starts at early developmental stages. In vitro, SCO-spondin promotes neuronal survival and differentiation, but its in vivo function still remains to be elucidated. Here we performed in vivo loss of function experiments for SCO-spondin during early brain development by injecting and electroporating a specific shRNA expression vector into the neural tube of chick embryos. We show that SCO-spondin knock down induces an increase in neuroepithelial cells proliferation concomitantly with a decrease in cellular differentiation toward neuronal lineages, leading to hyperplasia in both the diencephalon and the mesencephalon. In addition, SCO-spondin is required for the correct morphogenesis of the posterior commissure and pineal gland. Because SCO-spondin is secreted by the diencephalon, we sought to corroborate the long-range function of this protein in vitro by performing gain and loss of function experiments on mesencephalic explants. We find that culture medium enriched in SCO-spondin causes an increased neurodifferentiation of explanted mesencephalic region. Conversely, inhibitory antibodies against SCO-spondin cause a reduction in neurodifferentiation and an increase of mitosis when such explants are cultured in eCSF. Our results suggest that SCO-spondin is a crucial eCSF diffusible factor regulating the balance between proliferation and differentiation of the brain neuroepithelial cells. PMID:23761733

  4. A technique for cannulating the Cisterna magna and sampling cerebrospinal fluid from socially housed birds.

    PubMed

    Moore, M S; Kuenzel, W J; Mench, J A

    1994-04-01

    The measurement of central levels of neurochemicals is an important approach to the understanding of the neurophysiological basis of behavior patterns in animals. Previous studies have utilized central sampling techniques developed for individually housed animals. The purpose of this study was to develop a cannulation technique and a method for sampling cerebrospinal fluid (CSF) from socially housed birds to facilitate the study of the neurophysiological basis of social behaviors. The cannulation technique involved the surgical implantation of a 22-gauge concentric guide cannula into the cisterna magna of 16-wk-old, feed-restricted male broiler breeders (n = 6). Individual-specific coordinates and optimum angle and depth of implantation of the cannula were determined in order to place the cannula correctly in the designated site. Once implanted, the guide cannula proved to be unobtrusive and secure and did not attract aggressive pecking from other birds in the pen. Two methods of CSF sampling were then examined. The first method required the use of a push-pull perfusion pump to withdraw CSF at a rate of 1 to 2 microL/min. The second method (passive), which did not use a pump, involved simply removing a "dummy" cannula from the guide cannula to release the CSF, which was then collected with a glass Hamilton syringe. Samples ranging from 100 to 500 microL were collected using the passive method. The combination of the cannulation technique described and the passive sampling method proved to be the most simple, efficient, and reliable method for measuring central levels of neurochemicals in socially housed broiler breeder males. PMID:8202435

  5. Lumbar nerve rootlet entrapment by an iatrogenically spliced percutaneous intra-thecal lumbar cerebrospinal fluid catheter

    PubMed Central

    Yue, James J.; Castro, Carlos A.; Scott, David

    2015-01-01

    Background Complications associated with the use of percutaneous intra-thecal lumbar indwelling spinal catheters include infection, hematoma, neurologic dysfunction, and persistent undesired retention among others. A case of iatrogenic splicing associated with neurologic dysfunction with the use of a percutaneous intra-thecal indwelling spinal catheter is presented in this study. Method Single case study review. Results Review of case materials indicate Y pattern splicing/fragmentation of an indwelling intra-thecal catheter causing neurologic dysfunction and resistance to removal during attempted removal. Pain and weakness were evident soon after insertion of the catheter and were amplified with attempted catheter removal. Computed tomography revealed a double dot sign on axial view and a Y appearance on sagittal view. Surgical findings revealed entrapment of nerve rootlets in the axilla of the spliced catheter. Conclusions Splicing/fragmentation causing neurologic dysfunction as well as catheter retention is described as a potential complication of intra-thecal indwelling cerebrospinal fluid catheters. A symptom of fragmentation of a catheter may include neurologic dysfunction including pain and weakness of a lumbar nerve root. If resistance is experienced upon attempted catheter removal, with or without associated neurologic dysfunction, further attempts at removal should not be attempted. In those cases in which pain and/or lumbar weakness are evident post catheter placement and/or following attempted removal, computed tomography should be performed. If fragmentation of a catheter is evident on CT scan, spinal surgical consultation should be obtained. Recommended spinal surgical intervention includes an open durotomy and visualization of catheter fragments and nerve rootlets and removal of catheter fragments. PMID:25600724

  6. [Significance of measurement of serum and cerebrospinal fluid trace elements in the diagnosis of brain tumors].

    PubMed

    Jiang, H M

    1991-05-01

    Cu, Zn, Cd, Mn, Se in serum and Cu, Cd and Mn in cerebrospinal fluid (CSF) of 150 patients were measured by flame, flameless and hydride generation atomic absorption spectrophotometry. The patients were divided into three groups: malignant brain tumor group (MTG), benign brain tumor group (BTG), and non-neoplastic neurological disease group (no evidence of brain tumor group, NENG). The results were as follows: 1. Serum Cu, Zn, Cd, Mn, Se levels before operation were higher than those after operation; 2. Cu Cd, Mn serum levels were positively correlated with the CSF in the three groups. The correlation coefficients of serum Cu-CSFCU were 0.8935 (MTG), 0.6074 (BTG), 0.5349 NETG); serum Cd-CSFCd 0.7963, 0.2671, 0.5398; serum Mn- CSF Mn 0.5855, 0.4474, 0.5163, (P less than 0.01). 3. Serum and CSF Cu levels in MTG were significantly higher than in BTG and NETG (P less than 0.01). 4. A group of discrimination function equations was established with stepwise discrimination analysis. The six factors, i. e. serum Cu, Cd, Mn, Se and CSF Cu, Mn were significant in the equations. The conformation rate of diagnosis and discrimination by the equations in the malignant and benign brain tumors with clinical diagnosis was 81 percent. The equations could describe the relationship of coordination and antagonism among trace elements in serum and CSF. The authors believe that discrimination equations may have potential use both in diagnosing and discriminating patients in the 3 groups mentioned above and in following patients after excision of the brain tumor. PMID:1786758

  7. Potential error in ventriculocisternal perfusion method for determination of cerebrospinal fluid formation rate in cats.

    PubMed

    Marakovi?, Jurica; Oreskovi?, Darko; Jurjevi?, Ivana; Rados, Milan; Chudy, Darko; Klarica, Marijan

    2011-01-01

    The cerebrospinal fluid (CSF) formation rate (Vf) has been extensively studied by the ventriculocisternal perfusion, a method still regarded as the most precise one. This method as well as the equation for the calculation of the CSF formation rate (Vf) was established by Heisey et al on indicator dilution in perfusate. They assumed that the dilution of the indicator substance in perfusion is a consequence of newly formed CSF i.e. a higher CSF formation rate would result in a higher degree of dilution of the indicator substance. Therefore, such method is indirect and any mistake in the interpretation of the degree of indicator dilution would lead to questionable and often contradictory results regarding CSF formation rates. According to Heisey's equation, Vf shoud not depend on the rate of ventriculocisternal perfusion. However it has been shown that Vf is perfusion dependt value, and also that during perfusion the indicator substance is partially absorbed into surrounding tissue. It is possible that obtained Vf dependence on perfusion rate was caused by observed absorption of indicator substances. For that reason, in anaesthetised cats ventriculocisternal perfusion was performed at higher (252.0 microL/min) and at lower perfusion rate (65.5 microL/min) and Vf was calculated at both experimental and corrected (just for absorbed amount) values of indicator substance. Since (inspite of the correction) the difference of 12.4 microL/min between lower (15.0 microL/min) and higher perfusion rate (27.4 microL/min) was obtained, it is obvious that ventriculocisternal perfusion method cannot be considered reliable for measuring CSF formation rate. PMID:21648314

  8. Increased Interleukin-17 in Peripheral Blood and Cerebrospinal Fluid of Neurosyphilis Patients

    PubMed Central

    Wang, Cuini; Zhu, Lin; Gao, Zixiao; Guan, Zhifang; Lu, Haikong; Shi, Mei; Gao, Ying; Xu, Huanbin; Yang, X. Frank; Zhou, Pingyu

    2014-01-01

    Background Treponema pallidum infection evokes vigorous immune responses, resulting in tissue damage. Several studies have demonstrated that IL-17 may be involved in the pathogenesis of syphilis. However, the role of Th17 response in neurosyphilis remains unclear. Methodology/Principal Findings In this study, Th17 in peripheral blood from 103 neurosyphilis patients, 69 syphilis patients without neurological involvement, and 70 healthy donors were analyzed by flow cytometry. The level of IL-17 in cerebrospinal fluid (CSF) was quantified by ELISA. One-year follow up for 44 neurosyphilis patients was further monitored to investigate the role of Th17/IL-17 in neurosyphilis. We found that the frequency of Th17 cells was significantly increased in peripheral blood of patients with neurosyphilis, in comparison to healthy donors. IL-17 in CSF were detected from 55.3% neurosyphilis patients (in average of 2.29 (0–59.83) pg/ml), especially in those with symptomatic neurosyphilis (61.9%). CSF IL-17 was predominantly derived from Th17 cells in neurosyphilis patients. Levels of IL-17 in CSF of neurosyphilis patients were positively associated with total CSF protein levels and CSF VDRL (Venereal Disease Research Laboratory) titers. Notably, neurosyphilis patients with undetectable CSF IL-17 were more likely to confer to CSF VDRL negative after treatment. Conclusions These findings indicate that Th17 response may be involved in central nervous system damage and associated with clinical symptoms in neurosyphilis patients. Th17/IL-17 may be used as an alternative surrogate marker for assessing the efficacy of clinical treatment of neurosyphilis patients. PMID:25080350

  9. Neuropharmacokinetics of two investigational compounds in rats: divergent temporal profiles in the brain and cerebrospinal fluid.

    PubMed

    Tang, Cuyue; Chen, Ting; Kapadnis, Sudarshan; Hodgdon, Hilliary; Tao, Yi; Chen, Xing; Wen, Melody; Costa, Don; Murphy, Deirdre; Nolan, Scott; Flood, Dorothy G; Welty, Devin F; Koenig, Gerhard

    2014-10-15

    Two investigational compounds (FRM-1, (R)-7-fluoro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide and FRM-2, (R)-7-cyano-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide) resided in rat brain longer than in systemic circulation. In Caco-2 directional transport studies, they both showed good intrinsic passive permeability but differed significantly in efflux susceptibility (efflux ratio of <2 and ?7, respectively), largely attributed to P-glycoprotein (P-gp). Capitalizing on these interesting properties, we investigated how cerebrospinal fluid (CSF) concentration (CCSF) would be shaped by unbound plasma concentration (Cu,p) and unbound brain concentration (Cu,b) in disequilibrium conditions and at steady state. Following subcutaneous administration, FRM-1CCSF largely followed Cu,p initially and leveled between Cu,p and Cu,b. However, it gradually approached Cu,b and became lower than, but parallel to Cu,b at the terminal phase. In contrast, FRM-2CCSF temporal profile mostly paralleled the Cu,p but was at a much lower level. Upon intravenous infusion to steady state, FRM-1CCSF and Cu,b were similar, accounting for 61% and 69% of the Cu,p, indicating a case of largely passive diffusion-governed brain penetration where CCSF served as a good surrogate for Cu,b. On the contrary, FRM-2CCSF and Cu,b were remarkably lower than Cu,p (17% and 8% of Cu,p, respectively), suggesting that FRM-2 brain penetration was severely impaired by P-gp-mediated efflux and CCSF underestimated this impact. A semi-physiologically based pharmacokinetic (PBPK) model was constructed that adequately described the temporal profiles of the compounds in the plasma, brain and CSF. Our work provided some insight into the relative importance of blood-brain barrier (BBB) and blood-CSF barrier (BCSFB) in modulating CCSF. PMID:25091561

  10. Cerebrospinal Fluid Lysosomal Enzymes and Alpha-Synuclein in Parkinson's Disease

    PubMed Central

    Parnetti, Lucilla; Chiasserini, Davide; Persichetti, Emanuele; Eusebi, Paolo; Varghese, Shiji; Qureshi, Mohammad M; Dardis, Andrea; Deganuto, Marta; De Carlo, Claudia; Castrioto, Anna; Balducci, Chiara; Paciotti, Silvia; Tambasco, Nicola; Bembi, Bruno; Bonanni, Laura; Onofrj, Marco; Rossi, Aroldo; Beccari, Tommaso; El-Agnaf, Omar; Calabresi, Paolo

    2014-01-01

    To assess the discriminating power of multiple cerebrospinal fluid (CSF) biomarkers for Parkinson's disease (PD), we measured several proteins playing an important role in the disease pathogenesis. The activities of ?-glucocerebrosidase and other lysosomal enzymes, together with total and oligomeric ?-synuclein, and total and phosphorylated tau, were thus assessed in CSF of 71 PD patients and compared to 45 neurological controls. Activities of ?-glucocerebrosidase, ?-mannosidase, ?-hexosaminidase, and ?-galactosidase were measured with established enzymatic assays, while ?-synuclein and tau biomarkers were evaluated with immunoassays. A subset of PD patients (n = 44) was also screened for mutations in the ?-glucocerebrosidase-encoding gene (GBA1). In the PD group, ?-glucocerebrosidase activity was reduced (P < 0.05) and patients at earlier stages showed lower enzymatic activity (P < 0.05); conversely, ?-hexosaminidase activity was significantly increased (P < 0.05). Eight PD patients (18%) presented GBA1 sequence variations; 3 of them were heterozygous for the N370S mutation. Levels of total ?-synuclein were significantly reduced (P < 0.05) in PD, in contrast to increased levels of ?-synuclein oligomers, with a higher oligomeric/total ?-synuclein ratio in PD patients when compared with controls (P < 0.001). A combination of ?-glucocerebrosidase activity, oligomeric/total ?-synuclein ratio, and age gave the best performance in discriminating PD from neurological controls (sensitivity 82%; specificity 71%, area under the receiver operating characteristic curve = 0.87). These results demonstrate the possibility of detecting lysosomal dysfunction in CSF and further support the need to combine different biomarkers for improving the diagnostic accuracy of PD. PMID:24436092

  11. A common variant in ERBB4 regulates GABA concentrations in human cerebrospinal fluid.

    PubMed

    Luykx, Jurjen J; Vinkers, Christiaan H; Bakker, Steven C; Visser, Wouter F; van Boxmeer, Loes; Strengman, Eric; van Eijk, Kristel R; Lens, Judith A; Borgdorff, Paul; Keijzers, Peter; Kappen, Teus H; van Dongen, Eric P A; Bruins, Peter; Verhoeven, Nanda M; de Koning, Tom J; Kahn, René S; Ophoff, Roel A

    2012-08-01

    The neuregulin 1 (NRG1) receptor ErbB4 is involved in the development of cortical inhibitory GABAergic circuits and NRG1-ErbB4 signaling has been implicated in schizophrenia (SCZ). A magnetic resonance spectroscopy ((1)H-MRS) study has demonstrated that a single-nucleotide polymorphism in ERBB4, rs7598440, influences human cortical GABA concentrations. Other work has highlighted the significant impact of this genetic variant on expression of ERBB4 in the hippocampus and dorsolateral prefrontal cortex in human post mortem tissue. Our aim was to examine the association of rs7598440 with cerebrospinal fluid (CSF) GABA levels in healthy volunteers (n=155). We detected a significant dose-dependent association of the rs7598440 genotype with CSF GABA levels (G-allele standardized ?=-0.23; 95% CIs: -0.39 to -0.07; P=0.0066). GABA concentrations were highest in A homozygous, intermediate in heterozygous, and lowest in G homozygous subjects. When excluding subjects on psychotropic medication (three subjects using antidepressants), the results did not change (G-allele standardized ?=-0.23; 95% CIs: -0.40 to -0.07; P=0.0051). The explained variance in CSF GABA by rs7598440 in our model is 5.2% (P=0.004). The directionality of our findings agrees with the aforementioned (1)H-MRS and gene expression studies. Our observation therefore strengthens the evidence that the A-allele of rs7598440 in ERBB4 is associated with increased GABA concentrations in the human central nervous system (CNS). To our knowledge, our finding constitutes the first confirmation that CSF can be used to study genotype-phenotype correlations of GABA levels in the CNS. Such quantitative genetic analyses may be extrapolated to other CSF constituents relevant to SCZ in future studies. PMID:22549119

  12. A Common Variant in ERBB4 Regulates GABA Concentrations in Human Cerebrospinal Fluid

    PubMed Central

    Luykx, Jurjen J; Vinkers, Christiaan H; Bakker, Steven C; Visser, Wouter F; van Boxmeer, Loes; Strengman, Eric; van Eijk, Kristel R; Lens, Judith A; Borgdorff, Paul; Keijzers, Peter; Kappen, Teus H; van Dongen, Eric P A; Bruins, Peter; Verhoeven, Nanda M; de Koning, Tom J; Kahn, René S; Ophoff, Roel A

    2012-01-01

    The neuregulin 1 (NRG1) receptor ErbB4 is involved in the development of cortical inhibitory GABAergic circuits and NRG1-ErbB4 signaling has been implicated in schizophrenia (SCZ). A magnetic resonance spectroscopy (1H-MRS) study has demonstrated that a single-nucleotide polymorphism in ERBB4, rs7598440, influences human cortical GABA concentrations. Other work has highlighted the significant impact of this genetic variant on expression of ERBB4 in the hippocampus and dorsolateral prefrontal cortex in human post mortem tissue. Our aim was to examine the association of rs7598440 with cerebrospinal fluid (CSF) GABA levels in healthy volunteers (n=155). We detected a significant dose-dependent association of the rs7598440 genotype with CSF GABA levels (G-allele standardized ?=?0.23; 95% CIs: ?0.39 to ?0.07; P=0.0066). GABA concentrations were highest in A homozygous, intermediate in heterozygous, and lowest in G homozygous subjects. When excluding subjects on psychotropic medication (three subjects using antidepressants), the results did not change (G-allele standardized ?=?0.23; 95% CIs: ?0.40 to ?0.07; P=0.0051). The explained variance in CSF GABA by rs7598440 in our model is 5.2% (P=0.004). The directionality of our findings agrees with the aforementioned 1H-MRS and gene expression studies. Our observation therefore strengthens the evidence that the A-allele of rs7598440 in ERBB4 is associated with increased GABA concentrations in the human central nervous system (CNS). To our knowledge, our finding constitutes the first confirmation that CSF can be used to study genotype–phenotype correlations of GABA levels in the CNS. Such quantitative genetic analyses may be extrapolated to other CSF constituents relevant to SCZ in future studies. PMID:22549119

  13. Season of Sampling and Season of Birth Influence Serotonin Metabolite Levels in Human Cerebrospinal Fluid

    PubMed Central

    Luykx, Jurjen J.; Bakker, Steven C.; Lentjes, Eef; Boks, Marco P. M.; van Geloven, Nan; Eijkemans, Marinus J. C.; Janson, Esther; Strengman, Eric; de Lepper, Anne M.; Westenberg, Herman; Klopper, Kai E.; Hoorn, Hendrik J.; Gelissen, Harry P. M. M.; Jordan, Julian; Tolenaar, Noortje M.; van Dongen, Eric P. A.; Michel, Bregt; Abramovic, Lucija; Horvath, Steve; Kappen, Teus; Bruins, Peter; Keijzers, Peter; Borgdorff, Paul; Ophoff, Roel A.; Kahn, René S.

    2012-01-01

    Background Animal studies have revealed seasonal patterns in cerebrospinal fluid (CSF) monoamine (MA) turnover. In humans, no study had systematically assessed seasonal patterns in CSF MA turnover in a large set of healthy adults. Methodology/Principal Findings Standardized amounts of CSF were prospectively collected from 223 healthy individuals undergoing spinal anesthesia for minor surgical procedures. The metabolites of serotonin (5-hydroxyindoleacetic acid, 5-HIAA), dopamine (homovanillic acid, HVA) and norepinephrine (3-methoxy-4-hydroxyphenylglycol, MPHG) were measured using high performance liquid chromatography (HPLC). Concentration measurements by sampling and birth dates were modeled using a non-linear quantile cosine function and locally weighted scatterplot smoothing (LOESS, span?=?0.75). The cosine model showed a unimodal season of sampling 5-HIAA zenith in April and a nadir in October (p-value of the amplitude of the cosine?=?0.00050), with predicted maximum (PCmax) and minimum (PCmin) concentrations of 173 and 108 nmol/L, respectively, implying a 60% increase from trough to peak. Season of birth showed a unimodal 5-HIAA zenith in May and a nadir in November (p?=?0.00339; PCmax?=?172 and PCmin?=?126). The non-parametric LOESS showed a similar pattern to the cosine in both season of sampling and season of birth models, validating the cosine model. A final model including both sampling and birth months demonstrated that both sampling and birth seasons were independent predictors of 5-HIAA concentrations. Conclusion In subjects without mental illness, 5-HT turnover shows circannual variation by season of sampling as well as season of birth, with peaks in spring and troughs in fall. PMID:22312427

  14. Genome-wide association study of monoamine metabolite levels in human cerebrospinal fluid.

    PubMed

    Luykx, J J; Bakker, S C; Lentjes, E; Neeleman, M; Strengman, E; Mentink, L; DeYoung, J; de Jong, S; Sul, J H; Eskin, E; van Eijk, K; van Setten, J; Buizer-Voskamp, J E; Cantor, R M; Lu, A; van Amerongen, M; van Dongen, E P A; Keijzers, P; Kappen, T; Borgdorff, P; Bruins, P; Derks, E M; Kahn, R S; Ophoff, R A

    2014-02-01

    Studying genetic determinants of intermediate phenotypes is a powerful tool to increase our understanding of genotype-phenotype correlations. Metabolic traits pertinent to the central nervous system (CNS) constitute a potentially informative target for genetic studies of intermediate phenotypes as their genetic underpinnings may elucidate etiological mechanisms. We therefore conducted a genome-wide association study (GWAS) of monoamine metabolite (MM) levels in cerebrospinal fluid (CSF) of 414 human subjects from the general population. In a linear model correcting for covariates, we identified one locus associated with MMs at a genome-wide significant level (standardized ?=0.32, P=4.92 × 10(-8)), located 20 kb from SSTR1, a gene involved with brain signal transduction and glutamate receptor signaling. By subsequent whole-genome expression quantitative trait locus (eQTL) analysis, we provide evidence that this variant controls expression of PDE9A (?=0.21; P unadjusted=5.6 × 10(-7); P corrected=0.014), a gene previously implicated in monoaminergic transmission, major depressive disorder and antidepressant response. A post hoc analysis of loci significantly associated with psychiatric disorders suggested that genetic variation at CSMD1, a schizophrenia susceptibility locus, plays a role in the ratio between dopamine and serotonin metabolites in CSF. The presented DNA and mRNA analyses yielded genome-wide and suggestive associations in biologically plausible genes, two of which encode proteins involved with glutamate receptor functionality. These findings will hopefully contribute to an exploration of the functional impact of the highlighted genes on monoaminergic transmission and neuropsychiatric phenotypes. PMID:23319000

  15. Cerebrospinal fluid inflammatory cytokines and chemokines in naturally occurring canine spinal cord injury.

    PubMed

    Taylor, Amanda R; Welsh, C Jane; Young, Colin; Spoor, Erich; Kerwin, Sharon C; Griffin, John F; Levine, Gwendolyn J; Cohen, Noah D; Levine, Jonathan M

    2014-09-15

    Canine intervertebral disk herniation (IVDH) is a common, naturally occurring form of spinal cord injury (SCI) that is increasingly being used in pre-clinical evaluation of therapies. Although IVDH bears critical similarities to human SCI with respect to lesion morphology, imaging features, and post-SCI treatment, limited data are available concerning secondary injury mechanisms. Here, we characterized cerebrospinal fluid (CSF) cytokines, and chemokines in dogs with acute, surgically treated, thoracolumbar IVDH (n=39) and healthy control dogs (n=21) to investigate early inflammatory events after SCI. A bioplex system was used to measure interleukin (IL)-2, -6, -7, -8, -10, -15, and -18, granulocyte macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-?), keratinocyte chemoattractant (KC)-like protein, IFN-?-inducible protein-10, monocyte chemotactic protein 1 (MCP-1), and tumor necrosis factor alpha. Cytokine and chemokine concentrations in the CSF of healthy and SCI dogs were compared and, in SCI dogs, were correlated to the duration of SCI, behavioral measures of injury severity at the time of sampling, and neurological outcome 42 days post-SCI as determined by a validated ordinal score. IL-8 concentration was significantly higher in SCI cases than healthy controls (p=0.0013) and was negatively correlated with the duration of SCI (p=0.042). CSF MCP-1 and KC-like protein were positively correlated with CSF microprotein concentration in dogs with SCI (p<0.0001 and p=0.004). CSF MCP-1 concentration was negatively associated with 42-day postinjury outcome (p<0.0001). Taken together, these data indicate that cytokines and chemokines present after SCI in humans and rodent models are associated with SCI pathogenesis in canine IVDH. PMID:24786364

  16. Fructose Levels Are Markedly Elevated in Cerebrospinal Fluid Compared to Plasma in Pregnant Women

    PubMed Central

    Hwang, Janice J.; Johnson, Andrea; Cline, Gary; Belfort-DeAguiar, Renata; Snegovskikh, Denis; Khokhar, Babar; Han, Christina S.; Sherwin, Robert S.

    2015-01-01

    Background Fructose, unlike glucose, promotes feeding behavior in rodents and its ingestion exerts differential effects in the human brain. However, plasma fructose is typically 1/1000th of glucose levels and it is unclear to what extent fructose crosses the blood-brain barrier. We investigated whether local endogenous central nervous system (CNS) fructose production from glucose via the polyol pathway (glucose?sorbitol?fructose) contributes to brain exposure to fructose. Methods In this observational study, fasting glucose, sorbitol and fructose concentrations were measured using gas-chromatography-liquid mass spectroscopy in cerebrospinal fluid (CSF), maternal plasma, and venous cord blood collected from 25 pregnant women (6 lean, 10 overweight/obese, and 9 T2DM/gestational DM) undergoing spinal anesthesia and elective cesarean section. Results As expected, CSF glucose was ~60% of plasma glucose levels. In contrast, fructose was nearly 20-fold higher in CSF than in plasma (p < 0.001), and CSF sorbitol was ~9-times higher than plasma levels (p < 0.001). Moreover, CSF fructose correlated positively with CSF glucose (? 0.45, p = 0.02) and sorbitol levels (? 0.75, p < 0.001). Cord blood sorbitol was also ~7-fold higher than maternal plasma sorbitol levels (p = 0.001). There were no differences in plasma, CSF, and cord blood glucose, fructose, or sorbitol levels between groups. Conclusions These data raise the possibility that fructose may be produced endogenously in the human brain and that the effects of fructose in the human brain and placenta may extend beyond its dietary consumption. PMID:26035307

  17. Endostatin/collagen XVIII is increased in cerebrospinal fluid after severe traumatic brain injury.

    PubMed

    Chen, Hao; Xue, Li-Xia; Cao, He-Li; Chen, Shi-Wen; Guo, Yan; Gao, Wen-Wei; Ju, Shi-Ming; Tian, Heng-Li

    2013-01-01

    Recent studies have suggested that endogenous angiogenesis inhibitor endostatin/collagen XVIII might play an important role in the secondary brain injury following traumatic brain injury (TBI). In this study, we measured endostatin/collagen XVIII concentrations serially for 1 week after hospitalization by using the enzyme-linked immunosorbent assay method in the cerebrospinal fluid (CSF) of 30 patients with TBI and a Glasgow Coma Scale (GCS) score of 8 or less on admission. There was a significant trend toward increased CSF levels of endostatin after TBI versus control from 72?h after injury. In patients with GCS score of 3-5, CSF endostatin concentration was substantially higher at 72?h after injury than that in patients with GCS score of 6-8 (P < 0.05) and peaked rapidly at day 5 after injury, but decreased thereafter. The CSF endostatin concentration in 12 patients with an unfavorable outcome was significantly higher than that in 18 patients with a favorable outcome at day 5 (P = 0.043) and day 7 (P = 0.005) after trauma. Receiver operating characteristic curve analysis suggested a reliable operating point for the 7-day CSF endostatin concentration predicting poor prognosis to be 67.29?pg/mL. Our preliminary findings provide new evidence that endostatin/collagen XVIII concentration in the CSF increases substantially in patients with sTBI. Its dynamic change may have some clinical significance on the judgment of brain injury severity and the assessment of prognosis. This trial is registered with the ClinicalTrials.gov Identifier: NCT01846546. PMID:24089677

  18. Alterations in Cerebrospinal Fluid Proteins in a Presymptomatic Primary Glioma Model

    PubMed Central

    Whitin, John C.; Jang, Taichang; Merchant, Milton; Yu, Tom T-S.; Lau, Kenneth; Recht, Benjamin; Cohen, Harvey J.; Recht, Lawrence

    2012-01-01

    Background Understanding the early relationship between brain tumor cells and their environment could lead to more sensitive biomarkers and new therapeutic strategies. We have been using a rodent model of neurocarcinogenesis in which all animals develop brain tumors by six months of age to establish two early landmarks in glioma development: the appearance of a nestin+ cell at thirty days of age and the appearance of cellular hyperplasia between 60 and 120 days of age. We now report an assessment of the CSF proteome to determine the changes in protein composition that occur during this period. Materials and Methods Nestin+ cell clusters and microtumors were assessed in 63 ethylnitrosourea-exposed rats on 30, 60, and 90 days of age. CSF was obtained from the cisterna magna from 101 exposed and control rats at 30, 60, and 90 days and then analyzed using mass spectrometry. Differentially expressed peaks were isolated and identified. Results Nestin+ cells were noted in all ethylnitrosourea-exposed rats assessed pathologically. Small microtumors were noted in 0%, 18%, and 67% of 30-, 60-, and 90-day old rats, respectively (p<0.05, Chi square). False Discovery Rate analysis of peak intensities showed that the number of true discoveries with p<0.05 increased markedly with increasing age. Isolation and identification of highly differentially detected proteins at 90 days of age revealed increases in albumin and a fragment of ?1 macroglobulin and alterations in glutathionylated transthyretin. Conclusions The presence of increased albumin, fragments of cerebrospinal fluid proteins, and glutathione breakdown in temporal association with the development of cellular hyperplasia, suggests that, similar to many other systemic cancers, inflammation and oxidative stress is playing an important early role in the host’s response to brain tumor development and may be involved in affecting the early growth of brain tumor. PMID:23185417

  19. Diagnostic performance of amplified Mycobacterium tuberculosis direct test with cerebrospinal fluid, other nonrespiratory, and respiratory specimens.

    PubMed Central

    Pfyffer, G E; Kissling, P; Jahn, E M; Welscher, H M; Salfinger, M; Weber, R

    1996-01-01

    The Gen-Probe Amplified Mycobacterium tuberculosis Direct Test (MTD) was adapted to be used for cerebrospinal fluid (CSF) and a large variety of other nonrespiratory specimens. Standardized with artificially spiked dilution series of CSF, the modified MTD procedure consists of (i) increasing the amount of sample 10-fold, (ii) pretreating the specimen with a detergent, and (iii) increasing the amplification time from 2 to 3 h. Performance of MTD in a clinical mycobacteriology laboratory was tested over an extended period of time, involving a total of 322 nonrespiratory as well as 1,117 respiratory specimens from 998 patients. Results from MTD were compared with those from microscopy, culture, analysis of tuberculostearic acid by gas-liquid chromatography-mass spectrometry (CSF only), and the final clinical diagnosis. When MTD results were compared with resolved data, the sensitivity, specificity, and positive and negative predictive values for MTD were 93.1, 97.7, 90.0, and 98.5%, respectively, for nonrespiratory specimens and 86.6, 96.4, 76.8, and 98.1%, respectively, for respiratory specimens. Our data demonstrate that (i) MTD is a robust, highly sensitive and specific technique for the rapid detection of M. tuberculosis complex in all types of clinical specimens, (ii) there was no statistically significant difference (P > 0.005) in sensitivity and specificity for nonrespiratory compared with respiratory specimens, and (iii) repeating all MTDs which yield a result between 30,000 and 200,000 relative light units would help prevent a large number of false positives and, thus, enhance test specificity. PMID:8815093

  20. Concentration of soluble adhesion molecules in cerebrospinal fluid and serum of epilepsy patients.

    PubMed

    Luo, Jing; Wang, Wei; Xi, Zhiqin; Dan, Chen; Wang, Liang; Xiao, Zheng; Wang, Xuefeng

    2014-12-01

    Mounting evidence supports the involvement of brain inflammation and the associated blood-brain barrier damage from which spontaneous and recurrent seizures originate. Detection of the soluble form of adhesion molecules (AM) has also been proven to predict outcomes in central nervous system (CNS) disorders. A recent study has shown that expression of AM in brain vessels was upregulated 24 h after kainic acid (KA) induced seizures. The aim of the present study was to investigate soluble AM levels in the cerebrospinal fluid (CSF) and serum of epilepsy patients. Paired CSF and serum samples were analyzed by sandwich enzyme-linked immunosorbent assay (ELISA) to determine the concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1). Increased serum concentrations of sICAM-1 were present in epileptic patients (41 localization-related of unknown etiology, 19 idiopathic generalized). Serum sICAM-1 level in drug-refractory epilepsy was elevated as compared to new diagnosis epilepsy and drug-responsive epilepsy. CSF sVCAM-1 and serum sVCAM-1 concentrations in the epilepsy group were higher as compared to the neurosis group. Moreover, CSF sVCAM-1 and serum sVCAM-1 concentrations in drug-refractory epilepsy were raised as compared to drug-responsive epilepsy and new diagnosis epilepsy. However, there were no significant differences in concentrations of CSF sICAM-1 between the epilepsy and neurosis groups. Our results suggest that sVCAM-1 and sICAM-1 could play an important role in the drug-refractory epilepsy. PMID:25001004

  1. In Vitro Study of Cerebrospinal Fluid Dynamics in a Shaken Basal Cistern after Experimental Subarachnoid Hemorrhage

    PubMed Central

    Kertzscher, Ulrich; Schneider, Torsten; Goubergrits, Leonid; Affeld, Klaus; Hänggi, Daniel; Spuler, Andreas

    2012-01-01

    Background Cerebral arterial vasospasm leads to delayed cerebral ischemia and constitutes the major delayed complication following aneurysmal subarachnoid hemorrhage. Cerebral vasospasm can be reduced by increased blood clearance from the subarachnoid space. Clinical pilot studies allow the hypothesis that the clearance of subarachnoid blood is facilitated by means of head shaking. A major obstacle for meaningful clinical studies is the lack of data on appropriate parameters of head shaking. Our in vitro study aims to provide these essential parameters. Methodology/Principal Findings A model of the basal cerebral cistern was derived from human magnetic resonance imaging data. Subarachnoid hemorrhage was simulated by addition of dyed experimental blood to transparent experimental cerebrospinal fluid (CSF) filling the model of the basal cerebral cistern. Effects of various head positions and head motion settings (shaking angle amplitudes and shaking frequencies) on blood clearance were investigated using the quantitative dye washout method. Blood washout can be divided into two phases: Blood/CSF mixing and clearance. The major effect of shaking consists in better mixing of blood and CSF thereby increasing clearance rate. Without shaking, blood/CSF mixing and blood clearance in the basal cerebral cistern are hampered by differences in density and viscosity of blood and CSF. Blood clearance increases with decreased shaking frequency and with increased shaking angle amplitude. Head shaking facilitates clearance by varying the direction of gravitational force. Conclusions/Significance From this in vitro study can be inferred that patient or head shaking with large shaking angles at low frequency is a promising therapeutic strategy to increase blood clearance from the subarachnoid space. PMID:22870243

  2. Differences in cerebrospinal fluid inflammatory cell reaction of patients with leptomeningeal involvement by lymphoma and carcinoma.

    PubMed

    Illán, Julia; Simo, Marta; Serrano, Cristina; Castañón, Susana; Gonzalo, Raquel; Martínez-García, María; Pardo, Javier; Gómez, Lidia; Navarro, Miguel; Altozano, Javier Pérez; Alvarez, Ruth; Bruna, Jordi; Subirá, Dolores

    2014-12-01

    Dissemination of neoplastic cells into the cerebrospinal fluid (CSF) and leptomeninges is a devastating complication in patients with epithelial cell neoplasia (leptomeningeal carcinomatosis [LC]) and lymphomas (lymphomatous meningitis [LyM]). Information about the surrounding inflammatory cell populations is scarce. In this study, flow cytometry immunophenotyping was used to describe the distribution of the main leukocyte populations in the CSF of 83 patients diagnosed with neoplastic meningitis (LC, n = 65; LyM, n = 18). These data were compared with those obtained in the CSF from 55 patients diagnosed with the same groups of neoplasia without meningeal involvement (solid tumors, n = 36; high-grade lymphoma, n = 19). Median (interquartile) rates of lymphocytes, monocytes, and polymorphonuclear (PMN) cells were 59.7% (range, 35-76.6%), 24% (range, 16-53%), and 1.5% (range, 0-7.6%) in LC, respectively, and 98.5% (range, 70.8-100%), 1.5% (range, 0-29.3%), and 0% in LyM, respectively (P < 0.001). No difference was observed between patients with breast adenocarcinoma (n = 30) and lung adenocarcinoma (n = 21), nor with different rates of malignant CSF involvement. Patients with lymphoma (with or without LyM) had a similar CSF leukocyte distribution, but cancer patients with LC and without LC had a distinctive PMN cell rate (P = 0.002). These data show that CSF samples from patients with LC have a greater number of inflammatory cells and a different leukocyte distribution than seen in the CSF from patients with LyM. Description of PMN cells is a distinctive parameter of patients with LC, compared with the CSF from patients with LyM and patients with cancer but without LC. PMID:24746871

  3. Increased levels of cerebrospinal fluid JNK3 associated with amyloid pathology: links to cognitive decline

    PubMed Central

    Gourmaud, Sarah; Paquet, Claire; Dumurgier, Julien; Pace, Clarisse; Bouras, Constantin; Gray, Françoise; Laplanche, Jean-Louis; Meurs, Eliane F.; Mouton-Liger, François; Hugon, Jacques

    2015-01-01

    Background Alzheimer disease is characterized by cognitive decline, senile plaques of ?-amyloid (A?) peptides, neurofibrillary tangles composed of hyperphosphorylated ? proteins and neuronal loss. A? and ? are useful markers in the cerebrospinal fluid (CSF). C-Jun N-terminal kinases (JNKs) are serine-threonine protein kinases activated by phosphorylation and involved in neuronal death. Methods In this study, Western blots, enzyme-linked immunosorbent assay and histological approaches were used to assess the concentrations of A?, ? and JNK isoforms in postmortem brain tissue samples (10 Alzheimer disease and 10 control) and in CSF samples from 30 living patients with Alzheimer disease and 27 controls with neurologic disease excluding Alzheimer disease. Patients with Alzheimer disease were followed for 1–3 years and assessed using Mini–Mental State Examination scores. Results The biochemical and morphological results showed a significant increase of JNK3 and phosphorylated JNK levels in patients with Alzheimer disease, and JNK3 levels correlated with A?42 levels. Confocal microscopy revealed that JNK3 was associated with A? in senile plaques. The JNK3 levels in the CSF were significantly elevated in patients with Alzheimer disease and correlated statistically with the rate of cognitive decline in a mixed linear model. Limitations The study involved different samples grouped into 3 small cohorts. Evaluation of JNK3 in CSF was possible only with immunoblot analysis. Conclusion We found that JNK3 levels are increased in brain tissue and CSF from patients with Alzheimer disease. The finding that increased JNK3 levels in CSF could reflect the rate of cognitive decline is new and merits further investigation. PMID:25455349

  4. Role of adrenomedullin in the cerebrospinal fluid-contacting nucleus in the modulation of immobilization stress.

    PubMed

    Wu, Yue-Hong; Song, Si-Yuan; Liu, He; Xing, Dan; Wang, Xin; Fei, Yan; Li, Guang-Ling; Zhang, Chao; Li, Ying; Zhang, Li-Cai

    2015-06-01

    The contribution of the cerebrospinal fluid-contacting nucleus (CSF-contacting nucleus) and adrenomedullin (ADM) to the developmental modulation of stressful events remains controversial. This study explored the effects of endogenous ADM in the CSF-contacting nucleus on immobilization of stress-induced physiological parameter disorders and glucocorticoid hormone releasing hormone (CRH), rat plasma corticosterone expression, and verification of such effects by artificially lowering ADM expression in the CSF-contacting nucleus by targeted ablation of the nucleus. Immunohistochemical experiments showed that ADM-like immunoreactivity and the calcitonin receptor-like receptor (CRLR) marker were localized in the CSF-contacting nucleus. After 7 continuous days of chronic immobilization stress (CIS), animals exhibited anxiety-like behavior. Also, an increase in serum corticosterone, and enhanced expression of ADM in the CSF-contacting nucleus were observed, following activation by CIS. The intracerebroventricular (i.c.v.) administration of the ADM receptor antagonist AM22-52 significantly reduced ADM in the CSF-contacting nucleus, additionally, blocked the effects of ADM, meaning the expression of CRH in the hypothalamic paraventricular nucleus (Pa) and serum corticosterone level were increased, and the physiological parameters of the rats became correspondingly deteriorated. Additionally, the i.c.v. administration of cholera toxin subunit B-saporin (CB-SAP), a cytotoxin coupled to a cholera toxin subunit, completely eliminated the CSF-contacting nucleus, worsening the reaction of the body to CIS. The collective results demonstrated that ADM acted as a stress-related peptide in the CSF-contacting nucleus, and its lower expression and blocked effects in the nucleus contributed to the deterioration of stress-induced physiologic parameter disorders as well as the excessive expressions of stress-related hormones which were part of the hypothalamic-pituitary-adrenal (HPA) axis. PMID:25911494

  5. Cytokine Concentrations in the Cerebrospinal Fluid of Great Danes with Cervical Spondylomyelopathy

    PubMed Central

    Martin-Vaquero, P.; da Costa, R.C.; Moore, S.A.; Gross, A.C.; Eubank, T.D.

    2014-01-01

    Background Chronic inflammation is involved in the pathogenesis of human cervical spondylotic myelopathy and could also play a role in cervical spondylomyelopathy (CSM) in dogs. Hypothesis/Objectives That cerebrospinal fluid (CSF) cytokine concentrations would differ between clinically normal (control) and CSM-affected Great Danes (GDs), with affected GDs showing higher levels of inflammatory cytokines, such as interleukin (IL)-6 and monocyte chemoattractant protein-1/chemokine ligand 2 (MCP-1/CCL2). Animals Client-owned GDs: 15 control, 15 CSM-affected. Methods Prospective study. Dogs underwent cervical vertebral column magnetic resonance imaging and collection of CSF from the cerebellomedullary cistern. Cytokine concentrations were measured using a commercially available canine multiplex immunoassay. Cytokine concentrations were compared between groups. Associations with the administration of anti-inflammatory medications, disease duration and severity, severity of spinal cord (SC) compression, and SC signal changes were investigated in affected GDs. Results Affected GDs had significantly lower MCP-1/CCL2 (mean 138.03 pg/mL, 95% confidence interval [CI] = 114.85–161.20) than control GDs (212.89 pg/mL, 95% CI = 165.68–260.11, P = .028). In affected GDs, MCP-1/CCL2 concentrations correlated inversely with the severity of SC compression. There were no associations with administration of anti-inflammatory medications, disease duration, or disease severity. IL-6 concentrations were significantly higher (2.20 pg/mL, 95% CI = 1.92–2.47, P < .001) in GDs with SC signal changes. Conclusions and Clinical Importance Lower MCP-1/CCL2 in CSM-affected GDs might compromise clearance of axonal and myelin debris, delay axon regeneration, and affect recovery. Higher IL-6 in CSM-affected GDs with SC signal changes suggests more severe inflammation in this group. PMID:24965833

  6. Computational fluid dynamics modelling of cerebrospinal fluid pressure in Chiari malformation and syringomyelia.

    PubMed

    Clarke, Elizabeth C; Fletcher, David F; Stoodley, Marcus A; Bilston, Lynne E

    2013-07-26

    The pathogenesis of syringomyelia in association with Chiari malformation (CM) is unclear. Studies of patients with CM have shown alterations in the CSF velocity profile and these could contribute to syrinx development or enlargement. Few studies have considered the fluid mechanics of CM patients with and without syringomyelia separately. Three subject-specific CFD models were developed for a normal participant, a CM patient with syringomyelia and a CM patient without syringomyelia. Model geometries, CSF flow rate data and CSF velocity validation data were collected from MRI scans of the 3 subjects. The predicted peak CSF pressure was compared for the 3 models. An extension of the study performed geometry and flow substitution to investigate the relative effects of anatomy and CSF flow profile on resulting spinal CSF pressure. Based on 50 monitoring locations for each of the models, the CM models had significantly higher magnitude (p<0.01) peak CSF pressure compared with normal. When using the same CSF input flow waveform, changing the upper spinal geometry changed the magnitude of the CSF pressure gradient, and when using the same upper spinal geometry, changing the input flow waveform changed the timing of the peak pressure. This study may assist in understanding syringomyelia mechanisms and relative effects of CSF velocity profile and spinal geometry on CSF pressure. PMID:23769174

  7. Impact of Cerebrospinal Fluid Shunting for Idiopathic Normal Pressure Hydrocephalus on the Amyloid Cascade

    PubMed Central

    Moriya, Masao; Miyajima, Masakazu; Nakajima, Madoka; Ogino, Ikuko; Arai, Hajime

    2015-01-01

    The aim of this study was to determine whether the improvement of cerebrospinal fluid (CSF) flow dynamics by CSF shunting, can suppress the oligomerization of amyloid ?-peptide (A?), by measuring the levels of Alzheimer’s disease (AD)-related proteins in the CSF before and after lumboperitoneal shunting. Lumbar CSF from 32 patients with idiopathic normal pressure hydrocephalus (iNPH) (samples were obtained before and 1 year after shunting), 15 patients with AD, and 12 normal controls was analyzed for AD-related proteins and APLP1-derived A?-like peptides (APL1?) (a surrogate marker for A?). We found that before shunting, individuals with iNPH had significantly lower levels of soluble amyloid precursor proteins (sAPP) and A?38 compared to patients with AD and normal controls. We divided the patients with iNPH into patients with favorable (improvement ? 1 on the modified Rankin Scale) and unfavorable (no improvement on the modified Rankin Scale) outcomes. Compared to the unfavorable outcome group, the favorable outcome group showed significant increases in A?38, 40, 42, and phosphorylated-tau levels after shunting. In contrast, there were no significant changes in the levels of APL1?25, 27, and 28 after shunting. After shunting, we observed positive correlations between sAPP? and sAPP?, A?38 and 42, and APL1?25 and 28, with shifts from sAPP? to sAPP?, from APL1?28 to 25, and from A?42 to 38 in all patients with iNPH. Our results suggest that A? production remained unchanged by the shunt procedure because the levels of sAPP and APL1? were unchanged. Moreover, the shift of A? from oligomer to monomer due to the shift of A?42 (easy to aggregate) to A?38 (difficult to aggregate), and the improvement of interstitial-fluid flow, could lead to increased A? levels in the CSF. Our findings suggest that the shunting procedure can delay intracerebral deposition of A? in patients with iNPH. PMID:25821958

  8. Effect of Head Position on Cerebrospinal Fluid Pressure in Cats: Comparison with Artificial Model

    PubMed Central

    Klarica, Marijan; Radoš, Milan; Dragani?, Pero; Erceg, Gorislav; Oreškovi?, Darko; Marakovi?, Jurica; Bulat, Marin

    2006-01-01

    Aim To demonstrate that changes in the cerebrospinal fluid (CSF) pressure in the cranial cavity and spinal canal after head elevation from the horizontal level occur primarily due to the biophysical characteristics of the CSF system, ie, distensibility of the spinal dura. Methods Experiments in vivo were performed on cats and a new artificial model of the CSF system with dimensions similar to the CSF system in cats, consisting of non-distensible cranial and distensible spinal part. Measurements of the CSF pressure in the cranial and spinal spaces were performed in chloralose-anesthetized cats (n?=?10) in the horizontal position on the base of a stereotaxic apparatus (reference zero point) and in the position in which the head was elevated to 5 cm and 10 cm above that horizontal position. Changes in the CSF pressure in the cranial and spinal part of the model were measured in the cranial part positioned in the same way as the head in cats (n?=?5). Results When the cat was in the horizontal position, the values of the CSF pressure in the cranial (11.9?±?1.1 cm H2O) and spinal (11.8?±?0.6 cm H2O) space were not significantly different. When the head was elevated 5 cm or 10 cm above the reference zero point, the CSF pressure in the cranium significantly decreased to 7.7?±?0.6 cm H2O and 4.7?±?0.7 cm H2O, respectively, while the CSF pressure in the spinal space significantly increased to 13.8?±?0.7 cm H2O and 18.5?±?1.6 cm H2O, respectively (P<0.001 for both). When the artificial CSF model was positioned in the horizontal level and its cranial part elevated by 5 cm and 10 cm, the changes in the pressure were the same as those in the cats when in the same hydrostatic position. Conclusions The new model of the CSF system used in our study faithfully mimicked the changes in the CSF pressure in cats during head elevation in relation to the body. Changes in the pressure in the model were not accompanied by the changes in fluid volume in the non-distensible cranial part of the model. Thus, it seems that the changes in the CSF pressure occur due to the biophysical characteristics of the CSF system rather than the displacement of the blood and CSF volumes from the cranium to the lower part of body. PMID:16625687

  9. Impact of cerebrospinal fluid shunting for idiopathic normal pressure hydrocephalus on the amyloid cascade.

    PubMed

    Moriya, Masao; Miyajima, Masakazu; Nakajima, Madoka; Ogino, Ikuko; Arai, Hajime

    2015-01-01

    The aim of this study was to determine whether the improvement of cerebrospinal fluid (CSF) flow dynamics by CSF shunting, can suppress the oligomerization of amyloid ?-peptide (A?), by measuring the levels of Alzheimer's disease (AD)-related proteins in the CSF before and after lumboperitoneal shunting. Lumbar CSF from 32 patients with idiopathic normal pressure hydrocephalus (iNPH) (samples were obtained before and 1 year after shunting), 15 patients with AD, and 12 normal controls was analyzed for AD-related proteins and APLP1-derived A?-like peptides (APL1?) (a surrogate marker for A?). We found that before shunting, individuals with iNPH had significantly lower levels of soluble amyloid precursor proteins (sAPP) and A?38 compared to patients with AD and normal controls. We divided the patients with iNPH into patients with favorable (improvement ? 1 on the modified Rankin Scale) and unfavorable (no improvement on the modified Rankin Scale) outcomes. Compared to the unfavorable outcome group, the favorable outcome group showed significant increases in A?38, 40, 42, and phosphorylated-tau levels after shunting. In contrast, there were no significant changes in the levels of APL1?25, 27, and 28 after shunting. After shunting, we observed positive correlations between sAPP? and sAPP?, A?38 and 42, and APL1?25 and 28, with shifts from sAPP? to sAPP?, from APL1?28 to 25, and from A?42 to 38 in all patients with iNPH. Our results suggest that A? production remained unchanged by the shunt procedure because the levels of sAPP and APL1? were unchanged. Moreover, the shift of A? from oligomer to monomer due to the shift of A?42 (easy to aggregate) to A?38 (difficult to aggregate), and the improvement of interstitial-fluid flow, could lead to increased A? levels in the CSF. Our findings suggest that the shunting procedure can delay intracerebral deposition of A? in patients with iNPH. PMID:25821958

  10. Mass spectrometric analysis of cerebrospinal fluid protein for glioma and its clinical application

    PubMed Central

    Yu, Jiekai; Shen, Hong; Zhang, Jianmin; Liu, Weiguo; Chen, Zhe; He, Shuda; Zheng, Shu

    2014-01-01

    Aim of the study To establish and evaluate the fingerprint diagnostic models of cerebrospinal protein profile in glioma with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) and bioinformatics analysis, in order to seek new tumor markers. Material and methods SELDI-TOF-MS was used to detect the cerebrospinal protein bond to ProteinChip H4. The cerebrospinal protein profiles were obtained and analyzed using the artificial neural network (ANN) method. Fingerprint diagnostic models of cerebrospinal protein profiles for distinguishing glioma from non-brain-tumor, and distinguishing glioma from benign brain tumor, were established. The support vector machine (SVM) algorithm was used for verification of established diagnostic models. The tumor markers were screened. Results In a fingerprint diagnostic model of cerebrospinal protein profiles for distinguishing glioma from non-brain tumor, the sensitivity and specificity of glioma diagnosis were 100% and 91.7%, respectively. Seven candidate tumor markers were obtained. In a fingerprint diagnostic model for distinguishing glioma from benign brain tumor, the sensitivity and specificity of glioma diagnosis were 88.9% and 100%, respectively, and 8 candidate tumor markers were gained. Conclusions The combination of SELDI-TOF-MS and bioinformatics tools is a very effective method for screening and identifying new markers of glioma. The established diagnostic models have provided a new way for clinical diagnosis of glioma, especially for qualitative diagnosis. PMID:24966792

  11. The plasma and cerebrospinal fluid pharmacokinetics of the platinum analog satraplatin after intravenous administration in non-human primates

    Microsoft Academic Search

    Leigh Marcus; Robert Murphy; Elizabeth Fox; Cynthia McCully; Raphael Cruz; Katherine E. Warren; Thorsten Meyer; Edward McNiff; Frank M. Balis; Brigitte C. Widemann

    Background  Satraplatin is an orally bioavailable platinum analog with preclinical activity in cisplatin resistant models and clinical\\u000a activity in adults with refractory cancers. The cerebrospinal fluid (CSF) penetration of cisplatin and carboplatin in non-human\\u000a primates (NHP) is limited (3.7 and 2.6%, respectively). We evaluated the plasma and CSF pharmacokinetics (PK) of satraplatin\\u000a after an intravenous (IV) dose in NHP.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Satraplatin (120 mg\\/m2)

  12. Lack of usutu virus RNA in cerebrospinal fluid of patients with encephalitis of unknown etiology, Tuscany, Italy.

    PubMed

    Maggi, Fabrizio; Mazzetti, Paola; Focosi, Daniele; Macera, Lisa; Scagnolari, Carolina; Manzin, Aldo; Antonelli, Guido; Nelli, Luca Ceccherini

    2015-06-01

    Usutu virus (USUV) is an African mosquito-borne flavivirus associated with human neurological disorders in Europe. Recently, USUV introduction in Europe has been traced back to Eurasian blackbirds deaths in the Tuscany region of Italy in 1996. Ninety-six cerebrospinal fluid (CSF) samples from patients with encephalitis of unknown etiology diagnosed in 2010-2013 were screened to determine whether USUV circulates in humans in Tuscany. Using real-time polymerase chain reaction, no positive patient was found. USUV does not seem to cause neuroinvasive disorders in humans in Tuscany. PMID:25712912

  13. Utility of Measuring (1,3)-?-d-Glucan in Cerebrospinal Fluid for Diagnosis of Fungal Central Nervous System Infection

    PubMed Central

    Lyons, Jennifer L.; Thakur, Kiran T.; Lee, Rick; Watkins, Tonya; Pardo, Carlos A.; Carson, Kathryn A.; Markley, Barbara; Finkelman, Malcolm A.; Marr, Kieren A.; Roos, Karen L.

    2014-01-01

    (1-3)-?-d-Glucan (BDG) from cerebrospinal fluid (CSF) is a promising marker for diagnostic and prognostic aid of central nervous system (CNS) fungal infection, but its relationship to serum values has not been studied. Herein, we detected BDG from CSF at levels 2-fold lower than those in serum in patients without evidence of fungal disease but 25-fold higher than those in in serum in noncryptococcal CNS fungal infections. CSF BDG may be a useful biomarker in the evaluation of fungal CNS disease. PMID:25378578

  14. The effect of head orientation on subarachnoid cerebrospinal fluid distribution and its implications for neurophysiological modulation and recording techniques.

    PubMed

    Bijsterbosch, Janine D; Lee, Kwang-Hyuk; Hunter, Michael D; Wilkinson, Iain D; Farrow, Tom; Barker, Anthony T; Woodruff, Peter W R

    2013-03-01

    Gravitational forces may lead to local changes in subarachnoid cerebrospinal fluid (CSF) layer thickness, which has important implications for neurophysiological modulation and recording techniques. This study examines the effect of gravitational pull associated with different head positions on the distribution of subarachnoid CSF using structural magnetic resonance imaging. Images of seven subjects in three different positions (supine, left lateral and prone) were statistically compared. Results suggest that subarachnoid CSF volume decreases on the side of the head closest to the ground, due to downward brain movement with gravity. These findings warrant future research into currently unexplored gravitation-induced changes in regional subarachnoid CSF thickness. PMID:23400029

  15. The value of the measurement of cerebrospinal fluid levels of lysozyme in the diagnosis of neurological disease.

    PubMed Central

    Firth, G; Rees, J; McKeran, R O

    1985-01-01

    A turbidimetric technique has been adapted to yield maximum sensitivity for the measurement of lysozyme in cerebrospinal fluid. One hundred and ninety-eight patients were studied over a total period of 9 months using this technique. In addition to the considerably elevated levels known to occur in cases of bacterial and fungal meningitis, increased activity was also demonstrated in cases of subarachnoid haemorrhage and in certain inflammatory conditions. Normal or marginally increased levels were seen in cases of viral meningitis and encephalitis. PMID:4031917

  16. [Determination of neuropeptide Y concentration in the cerebrospinal fluid in patients with cerebrovascular diseases and its significance].

    PubMed

    Cao, X H; Kang, D X; Yang, L H

    1991-07-01

    Concentration of neuropeptide Y (NPY) in the cerebrospinal fluid (CSF) of patients with cerebrovascular diseases was measured by using radioimmunoassay. The results showed that NPY concentration in CSF in patients with hemorrhagic cerebrovascular diseases (HCVD) was 4148 +/- 397.2 pg/ml, being significantly higher than the control level of 1083.7 +/- 245.8 pg/ml. While the NPY concentration in CSF of patients with ischemic cerebrovascular diseases (ICVD) was 2214 +/- 289.2 pg/ml, being not significantly different from the level in the control group. The effect of NPY in vasospasm after HCVD was preliminarily discussed. PMID:1752158

  17. Magnetic resonance imaging and cerebrospinal fluid immunoassay in the diagnosis of cerebral schistosomiasis: experience in southwest China.

    PubMed

    Wan, Heng; Masataka, Hayashi; Lei, Ting; Li, Ming

    2009-10-01

    We analysed the magnetic resonance imaging (MRI) clinical characteristics as well as serum and cerebrospinal fluid (CSF) immunoassay results in 41 patients with cerebral schistosomiasis. Thirty-five cerebral schistosomiasis patients were diagnosed by imaging and immunoassay, five by post-operative pathological examination and one by diagnostic treatment with praziquantel. We found that MRI showed specific enhancement, forming the 'Buddha's hand' appearance. Although this pattern of MRI enhancement may not be present in all cases of cerebral schistosomiasis, when it is observed a diagnosis of cerebral schistosomiasis should be considered. Meanwhile, CSF immunoassay may also play an important role in the differential diagnosis of cerebral schistosomiasis. PMID:19439334

  18. Evaluation of S100B in cerebrospinal fluid as a potential biomarker for neurological diseases in calves

    PubMed Central

    KOJIMA, Yuka; CHIBA, Shiori; HORIUCHI, Noriyuki; KOBAYASHI, Yoshiyasu; INOKUMA, Hisashi

    2015-01-01

    S100B in cerebrospinal fluid (CSF-S100B) was measured in calves with 20 neurologic and 21 non-neurologic diseases to clarify its utility as a biomarker for neurologic diseases. The median CSF-S100B value in the neurologic disease group (43.0 ng/ml) was significantly higher than that in the non-neurologic disease group (10.2 ng/ml). As CSF-S100B levels in calves with neurologic diseases widely differed, the utility of CSF-S100B as a diagnostic marker for neurologic diseases in cattle remains inconclusive. PMID:25649061

  19. Cerebrospinal Fluid P-Tau181P: Biomarker for Improved Differential Dementia Diagnosis

    PubMed Central

    Struyfs, Hanne; Niemantsverdriet, Ellis; Goossens, Joery; Fransen, Erik; Martin, Jean-Jacques; De Deyn, Peter P.; Engelborghs, Sebastiaan

    2015-01-01

    The goal of this study is to investigate the value of tau phosphorylated at threonine 181 (P-tau181P) in the Alzheimer’s disease (AD) cerebrospinal fluid (CSF) biomarker panel for differential dementia diagnosis in autopsy confirmed AD and non-AD patients. The study population consisted of 140 autopsy confirmed AD and 77 autopsy confirmed non-AD dementia patients. CSF concentrations of amyloid-? peptide of 42 amino acids (A?1–42), total tau protein (T-tau), and P-tau181P were determined with single analyte ELISA-kits (INNOTEST®, Fujirebio, Ghent, Belgium). Diagnostic accuracy was assessed through receiver operating characteristic (ROC) curve analyses to obtain area under the curve (AUC) values and to define optimal cutoff values to discriminate AD from pooled and individual non-AD groups. ROC curve analyses were only performed on biomarkers and ratios that differed significantly between the groups. Pairwise comparison of AUC values was performed by means of DeLong tests. The A?1–42/P-tau181P ratio (AUC?=?0.770) performed significantly better than A?1–42 (AUC?=?0.677, P?=?0.004), T-tau (AUC?=?0.592, P?

  20. Detection of 65 kD heat shock protein in cerebrospinal fluid of tuberculous meningitis patients

    PubMed Central

    Mudaliar, Anju V; Kashyap, Rajpal S; Purohit, Hemant J; Taori, Girdhar M; Daginawala, Hatim F

    2006-01-01

    Background Diagnosis of tuberculous meningitis (TBM) is difficult. Rapid confirmatory diagnosis is essential to initiate required therapy. There are very few published reports about the diagnostic significance of 65 kD heat shock protein (hsp) in TBM patients, which is present in a wide range of Mycobacterium tuberculosis species and elicits a cellular and humoral immune response. In the present study we have conducted a prospective evaluation for the demonstration of 65 kD hsp antigen in cerebrospinal fluid (CSF) of TBM patients, by indirect ELISA method using monoclonal antibodies (mAb) against the 65 kD hsp antigen, for the diagnosis of TBM. Methods A total of 160 CSF samples of different groups of patients (confirmed TBM {n = 18}, clinically suspected TBM {n = 62}, non TBM infectious meningitis {n = 35} and non-infectious neurological diseases {n = 45}) were analyzed by indirect ELISA method using mAb to 65 kD hsp antigen. The Kruskal Wallis test (Non-Parametric ANOVA) with the Dunnett post test was used for statistical analysis. Results The indirect ELISA method yielded 84% sensitivity and 90% specificity for the diagnosis of TBM using mAb to 65 kD hsp antigen. The mean absorbance value of 65 kD hsp antigen in TBM patients was [0.70 ± 0.23 (0.23–1.29)], significantly higher than the non-TBM infectious meningitis group [0.32 ± 0.14 (0.12–0.78), P < 0.001] and also higher than the non-infectious neurological disorders group [0.32 ± 0.13 (0.20–0.78), P < 0.001]. A significant difference in the mean absorbance of 65 kD hsp antigen was noted in the CSF of culture-positive TBM patients [0.94 ± 0.18 (0.54–1.29)] when compared with clinically suspected TBM patients [0.64 ± 0.20 (0.23–0.98), P < 0.05]. Conclusion The presence of 65 kD hsp antigen in the CSF of confirmed and suspected cases of TBM would indicate that the selected protein is specific to M. tuberculosis and could be considered as a diagnostic marker for TBM. PMID:16978411

  1. The cerebrospinal fluid proteome in HIV infection: change associated with disease severity.

    SciTech Connect

    Angel, Thomas E.; Jacobs, Jon M.; Spudich, Serena S.; Gritsenko, Marina A.; Fuchs, Dietmar; Liegler, Teri; Zetterberg, Henrik; Camp, David G.; Price, Richard W.; Smith, Richard D.

    2012-03-20

    Central nervous system (CNS) infection is a constant feature of systemic HIV infection with a clinical spectrum that ranges from chronic asymptomatic infection to severe cognitive and motor dysfunction. Analysis of cerebrospinal fluid (CSF) has played an important part in defining the character of this evolving infection and response to treatment. To further characterize CNS HIV infection and its effects, we applied advanced high-throughput proteomic methods to CSF to identify novel proteins and their changes with disease progression and treatment. After establishing an accurate mass and time (AMT) tag database containing 23,141 AMT tags for CSF peptides, we analyzed 91 CSF samples by LC-MS from 12 HIV-uninfected and 14 HIV-infected subjects studied in the context of initiation of antiretroviral and correlated abundances of identified proteins (a) within and between subjects, (b) with all other proteins across the entire sample set, and (c) with 'external' CSF biomarkers of infection (HIV RNA), immune activation (neopterin) and neural injury (neurofilament light chain protein, NFL). We identified a mean of 2,333 +/- 328 (SD) peptides covering 307 +/-16 proteins in the 91 CSF sample set. Protein abundances differed both between and within subjects sampled at different time points and readily separated those with and without HIV infection. Proteins also showed inter-correlations across the sample set that were associated with biologically relevant dynamic processes. One-hundred and fifty proteins showed correlations with the external biomarkers. For example, using a threshold of cross correlation coefficient (Pearson's) {le}0.3 and {ge}0.3 for potentially meaningful relationships, a total of 99 proteins correlated with CSF neopterin (43 negative and 56 positive correlations) and related principally to neuronal plasticity and survival and to innate immunity. Pathway analysis defined several networks connecting the identified proteins, including one with amyloid precursor protein as a central node. Advanced CSF proteomic analysis enabled the identification of an array of novel protein changes across the spectrum of CNS HIV infection and disease. This initial analysis clearly demonstrated the value of contemporary state-of-the-art proteomic CSF analysis as a discovery tool in HIV infection with likely similar application to other neurological inflammatory and degenerative diseases.

  2. The choroid plexus-cerebrospinal fluid system: from development to aging.

    PubMed

    Redzic, Zoran B; Preston, Jane E; Duncan, John A; Chodobski, Adam; Szmydynger-Chodobska, Joanna

    2005-01-01

    The function of the cerebrospinal fluid (CSF) and the tissue that secretes it, the choroid plexus (CP), has traditionally been thought of as both providing physical protection to the brain through buoyancy and facilitating the removal of brain metabolites through the bulk drainage of CSF. More recent studies suggest, however, that the CP-CSF system plays a much more active role in the development, homeostasis, and repair of the central nervous system (CNS). The highly specialized choroidal tissue synthesizes trophic and angiogenic factors, chemorepellents, and carrier proteins, and is strategically positioned within the ventricular cavities to supply the CNS with these biologically active substances. Through polarized transport systems and receptor-mediated transcytosis across the choroidal epithelium, the CP, a part of the blood-CSF barrier (BCSFB), controls the entry of nutrients, such as amino acids and nucleosides, and peptide hormones, such as leptin and prolactin, from the periphery into the brain. The CP also plays an important role in the clearance of toxins and drugs. During CNS development, CP-derived growth factors, such as members of the transforming growth factor-beta superfamily and retinoic acid, play an important role in controlling the patterning of neuronal differentiation in various brain regions. In the adult CNS, the CP appears to be critically involved in neuronal repair processes and the restoration of the brain microenvironment after traumatic and ischemic brain injury. Furthermore, recent studies suggest that the CP acts as a nursery for neuronal and astrocytic progenitor cells. The advancement of our knowledge of the neuroprotective capabilities of the CP may therefore facilitate the development of novel therapies for ischemic stroke and traumatic brain injury. In the later stages of life, the CP-CSF axis shows a decline in all aspects of its function, including CSF secretion and protein synthesis, which may in themselves increase the risk for development of late-life diseases, such as normal pressure hydrocephalus and Alzheimer's disease. The understanding of the mechanisms that underlie the dysfunction of the CP-CSF system in the elderly may help discover the treatments needed to reverse the negative effects of aging that lead to global CNS failure. PMID:16344101

  3. Cerebrospinal fluid mitochondrial DNA – a novel DAMP in pediatric traumatic brain injury

    PubMed Central

    Walko, Thomas D.; Bola, R. Aaron; Hong, John D.; Au, Alicia K; Bell, Michael J; Kochanek, Patrick M.; Clark, Robert S. B; Aneja, Rajesh K.

    2014-01-01

    Background Danger associated molecular patterns (DAMPs) are nuclear or cytoplasmic proteins that are released from the injured tissues and activate the innate immune system. Mitochondrial DNA (mtDNA) is a novel DAMP that is released into the extracellular milieu subsequent to cell death and injury. We hypothesized that cell death within the central nervous system in children with traumatic brain injury (TBI) would lead to release of mtDNA into the cerebrospinal fluid (CSF) and has the potential to predict the outcome after trauma. Methods CSF was collected from children with severe TBI that required intracranial pressure monitoring with Glasgow Coma Scale (GCS) scores ? 8 via an externalized ventricular drain. Control CSF was obtained in children without TBI or meningoencephalitis that demonstrated no leukocytes in the diagnostic lumbar puncture. Results The median age for patients with TBI was 6.3 y and 62% were male. The common mechanisms of injury included motor vehicle collision (35.8%) followed by falls (21.5%) and inflicted TBI (19%); 6 children (14.2%) died during their ICU course. The mean CSF mtDNA concentration was 1.10E +05 ± 2.07E+05 and 1.63E+03 ± 1.80E+03 copies/µL in the pediatric TBI and control population respectively. Furthermore, the mean CSF mtDNA concentration in pediatric patients who later died or had severe disability was significantly higher than that of the survivors (1.63E+ 05 ± 2.77E+05 vs. 5.05E+04 ± 6.21E+04 copies/µL) (p<0.0001). We found a significant correlation between CSF mtDNA and HMGB1, another prototypical DAMP, concentrations (? = 0.574, p<0.05), supporting the notion that both DAMPs are increased in the CSF following TBI. Conclusions Our data suggest that CSF mtDNA is novel DAMP in TBI, and appears to be a useful biomarker that correlates with neurological outcome after TBI. Further inquiry into the components of mtDNA that modulate the innate immune response will be helpful in understanding the mechanism of local and systemic inflammation after TBI. PMID:24667615

  4. MGMT promoter methylation in serum and cerebrospinal fluid as a tumor-specific biomarker of glioma

    PubMed Central

    WANG, ZHENG; JIANG, WEI; WANG, YAHONG; GUO, YANG; CONG, ZHENG; DU, FANGFANG; SONG, BIN

    2015-01-01

    O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation is a conventional technique to predict the prognosis or individualized treatment of glioma in tumor tissue following surgery or biopsy. However, the technique cannot be applied in those glioma patients with concomitant neurological dysfunctions or advanced age. The present study aimed to find a new minimally invasive and efficient alternative method for the detection of MGMT promoter methylation. The expression of MGMT promoter methylation was assessed in peripheral blood and cerebrospinal fluid (CSF), and compared to the corresponding tumor tissue from glioma patients. The 89 patients in the study [32 World Health Organization (WHO) grade II, 19 WHO grade III and 38 WHO grade IV) were pathologically-diagnosed glioma and received radiation therapy following sample collection. The resected glioma tumor tissue (89), corresponding serum (89) and CSF (78) samples were collected for the detection of MGMT promoter methylation using methylation-specific polymerase chain reaction. The sensitivity and specificity of detecting MGMT promoter methylation in CSF and serum were compared. Among the tumor tissue samples, 51/89 (57.3%) showed MGMT promoter methylation. The specificity of the detection in the CSF and serum samples reached 100%. The sensitivity of MGMT promoter methylation detection in CSF and serum were 26/40 (65.0%) and 19/51 (37.3%), respectively (P<0.05). In the WHO II, III and IV subgroups, the sensitivities of MGMT promoter methylation detection using CSF were 8/12 (66.7%), 11/18 (61.1%) and 7/10 (70.0%), respectively, which were significantly higher than the sensitivities using serum (7/21, 33.3%; 7/19, 36.8%; and 5/11, 45.5%, respectively P<0.05). Among patients with residual postoperative tumors, the sensitivities of detecting MGMT promoter methylation using CSF and serum were 18/25 (72.0%) and 10/24 (41.7%), respectively, both of which were significantly higher than the corresponding values for patients without residual tumors (8/15, 53.3% and 6/19, 31.6%, respectively; P<0.05). The detection of MGMT promoter methylation in CSF specimens shows higher sensitivity compared to the serum for glioma patients. Assessment of MGMT promoter methylation in CSF may provide a promising clinical methodology for early diagnosis, individual treatment, monitoring of recurrence and prognosis for glioma patients. PMID:26171163

  5. Quantification of mutant huntingtin protein in cerebrospinal fluid from Huntington’s disease patients

    PubMed Central

    Wild, Edward J.; Boggio, Roberto; Langbehn, Douglas; Robertson, Nicola; Haider, Salman; Miller, James R.C.; Zetterberg, Henrik; Leavitt, Blair R.; Kuhn, Rainer; Tabrizi, Sarah J.; Macdonald, Douglas; Weiss, Andreas

    2015-01-01

    BACKGROUND: Quantification of disease-associated proteins in the cerebrospinal fluid (CSF) has been critical for the study and treatment of several neurodegenerative disorders; however, mutant huntingtin protein (mHTT), the cause of Huntington’s disease (HD), is at very low levels in CSF and, to our knowledge, has never been measured previously. METHODS: We developed an ultrasensitive single-molecule counting (SMC) mHTT immunoassay that was used to quantify mHTT levels in CSF samples from individuals bearing the HD mutation and from control individuals in 2 independent cohorts. RESULTS: This SMC mHTT immunoassay demonstrated high specificity for mHTT, high sensitivity with a femtomolar detection threshold, and a broad dynamic range. Analysis of the CSF samples showed that mHTT was undetectable in CSF from all controls but quantifiable in nearly all mutation carriers. The mHTT concentration in CSF was approximately 3-fold higher in patients with manifest HD than in premanifest mutation carriers. Moreover, mHTT levels increased as the disease progressed and were associated with 5-year onset probability. The mHTT concentration independently predicted cognitive and motor dysfunction. Furthermore, the level of mHTT was associated with the concentrations of tau and neurofilament light chain in the CSF, suggesting a neuronal origin for the detected mHTT. CONCLUSIONS: We have demonstrated that mHTT can be quantified in CSF from HD patients using the described SMC mHTT immunoassay. Moreover, the level of mHTT detected is associated with proximity to disease onset and diminished cognitive and motor function. The ability to quantify CSF mHTT will facilitate the study of HD, and mHTT quantification could potentially serve as a biomarker for the development and testing of experimental mHTT-lowering therapies for HD. TRIAL REGISTRATION: Not applicable. FUNDING: CHDI Foundation Inc.; Medical Research Council (MRC) UK; National Institutes for Health Research (NIHR); Rosetrees Trust; Swedish Research Council; and Knut and Alice Wallenberg Foundation. PMID:25844897

  6. Diet Intervention and Cerebrospinal Fluid Biomarkers in Amnestic Mild Cognitive Impairment

    PubMed Central

    Bayer-Carter, Jennifer L.; Green, Pattie S.; Montine, Thomas J.; VanFossen, Brian; Baker, Laura D.; Watson, G. Stennis; Bonner, Laura M.; Callaghan, Maureen; Leverenz, James B.; Walter, Brooke K.; Tsai, Elaine; Plymate, Stephen R.; Postupna, Nadia; Wilkinson, Charles W.; Zhang, Jing; Lampe, Johanna; Kahn, Steven E.; Craft, Suzanne

    2011-01-01

    Objective To compare the effects of a 4-week high–saturated fat/high–glycemic index (HIGH) diet with a low–saturated fat/low–glycemic index (LOW) diet on insulin and lipid metabolism, cerebrospinal fluid (CSF) markers of Alzheimer disease, and cognition for healthy adults and adults with amnestic mild cognitive impairment (aMCI). Design Randomized controlled trial. Setting Veterans Affairs Medical Center clinical research unit. Participants Forty-nine older adults (20 healthy adults with a mean [SD] age of 69.3 [7.4] years and 29 adults with aMCI with a mean [SD] age of 67.6 [6.8] years). Intervention Participants received the HIGH diet (fat, 45% [saturated fat, >25%]; carbohydrates, 35%–40% [glycemic index, >70]; and protein, 15%–20%) or the LOW diet (fat, 25%; [saturated fat, <7%]; carbohydrates, 55%–60% [glycemic index, <5]; and protein, 15%–20%) for 4 weeks. Cognitive tests, an oral glucose tolerance test, and lumbar puncture were conducted at baseline and during the fourth week of the diet. Main Outcome Measures The CSF concentrations of ?-amyloid (A?42 and A?40), tau protein, insulin, F2-isoprostanes, and apolipoprotein E, plasma lipids and insulin, and measures of cognition. Results For the aMCI group, the LOW diet increased CSF A?42 concentrations, contrary to the pathologic pattern of lowered CSF A?42 typically observed in Alzheimer disease. The LOW diet had the opposite effect for healthy adults, ie, decreasing CSF A?42, whereas the HIGH diet increased CSF A?42. The CSF apolipoprotein E concentration was increased by the LOW diet and decreased by the HIGH diet for both groups. For the aMCI group, the CSF insulin concentration increased with the LOW diet, but the HIGH diet lowered the CSF insulin concentration for healthy adults. The HIGH diet increased and the LOW diet decreased plasma lipids, insulin, and CSF F2-isoprostane concentrations. Delayed visual memory improved for both groups after completion of 4 weeks of the LOW diet. Conclusion Our results suggest that diet may be a powerful environmental factor that modulates Alzheimer disease risk through its effects on central nervous system concentrations of A?42, lipoproteins, oxidative stress, and insulin. PMID:21670398

  7. The formation of cerebrospinal fluid: nearly a hundred years of interpretations and misinterpretations.

    PubMed

    Oreskovi?, D; Klarica, M

    2010-09-24

    The first scientific and experimental approaches to the study of cerebrospinal fluid (CSF) formation began almost a hundred years ago. Despite researchers being interested for so long, some aspects of CSF formation are still insufficiently understood. Today it is generally believed that CSF formation is an active energy consuming metabolic process which occurs mainly in brain ventricles, in choroid plexuses. CSF formation, together with CSF absorption and circulation, represents the so-called classic hypothesis of CSF hydrodynamics. In spite of the general acceptance of this hypothesis, there is a considerable series of experimental results that do not support the idea of the active nature of CSF formation and the idea that choroid plexuses inside the brain ventricles are the main places of formation. The main goal of this review is to summarize the present understanding of CSF formation and compare this understanding to contradictory experimental results that have been obtained so far. And finally, to try to offer a physiological explanation by which these contradictions could be avoided. We therefore analyzed the main methods that study CSF formation, which enabled such an understanding, and presented their shortcomings, which could also be a reason for the erroneous interpretation of the obtained results. A recent method of direct aqueductal determination of CSF formation is shown in more detail. On the one hand, it provides the possibility of direct insight into CSF formation, and on the other, it clearly indicates that there is no net CSF formation inside the brain ventricles. These results are contradictory to the classic hypothesis and, together with other mentioned contradictory results, strongly support a recently proposed new working hypothesis on the hydrodynamics of CSF. According to this new working hypothesis, CSF is permanently produced and absorbed in the whole CSF system as a consequence of filtration and reabsorption of water volume through the capillary walls into the surrounding brain tissue. The CSF exchange between the entire CSF system and the surrounding tissue depends on (patho)physiological conditions that predominate within those compartments. PMID:20435061

  8. Assessing cerebrospinal fluid abnormalities in neurosyphilis patients without human immunodeficiency virus infection.

    PubMed

    Liu, Li-Li; Zhang, Hui-Lin; Huang, Song-Jie; Liu, Long; Tong, Man-Li; Lin, Li-Rong; Chen, Yu-Yan; Xi, Ya; Guo, Xiao-Jing; Zhang, Ya-Feng

    2013-12-01

    Neurosyphilis (NS) caused by Treponema pallidum (T. pallidum) subspecies pallidum, can affect the central nervous system during any stage of the disease. To assess several laboratory parameters for NS diagnosis, we performed a case control study on 42 hospitalized NS patients negative for human immunodeficiency virus (HIV) and 40 syphilis/non-NS patients, excluding NS patients at Xiamen Zhongshan Hospital from June 2010 to June 2011. Multivariate logistic regression model showed that the cerebrospinal fluid white blood cell (CSF-WBC, P = 0.009) levels, the CSF-LDH (P = 0.006) levels, the albumin quotient (P = 0.009) and the IgA index (P = 0.042) were independently associated with high risk of NS. The receiver operator characteristic (ROC) curve analysis revealed that the optimal cut-offs were 10 × 106 cells/L for the CSF-WBC concentration, 19.3 U/L for the CSF lactate dehydrogenase (LDH) concentration, 7.08 for the albumin quotient, and 0.14 for the IgA index. Combining the CSF-WBC level, the CSF-LDH level, the albumin quotient and the IgA index increased the NS diagnosis sensitivity to 97.6%. T. pallidum particle agglutination (TPPA) index significantly correlated with the CSF-WBC (r = 0.453, P = 0.000), the IgA index (r = 0.446, P = 0.000), the albumin quotient (r = 0.262, P = 0.017), and the CSF-LDH (r = ? 0.278, P = 0.012), respectively. In addition, there were correlations between the CSF-WBC and the IgA index (r = 0.329, P = 0.003), and between the CSF-WBC and the albumin quotient (r = 0.306, P = 0.005). Our results indicated that simultaneous testing of CSF-WBC levels, albumin quotient, IgA index and CSF-LDH can help predict the likelihood of NS in HIV-negative patients. PMID:24459685

  9. Cerebrospinal Fluid P-Tau181P: Biomarker for Improved Differential Dementia Diagnosis.

    PubMed

    Struyfs, Hanne; Niemantsverdriet, Ellis; Goossens, Joery; Fransen, Erik; Martin, Jean-Jacques; De Deyn, Peter P; Engelborghs, Sebastiaan

    2015-01-01

    The goal of this study is to investigate the value of tau phosphorylated at threonine 181 (P-tau181P) in the Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker panel for differential dementia diagnosis in autopsy confirmed AD and non-AD patients. The study population consisted of 140 autopsy confirmed AD and 77 autopsy confirmed non-AD dementia patients. CSF concentrations of amyloid-? peptide of 42 amino acids (A?1-42), total tau protein (T-tau), and P-tau181P were determined with single analyte ELISA-kits (INNOTEST(®), Fujirebio, Ghent, Belgium). Diagnostic accuracy was assessed through receiver operating characteristic (ROC) curve analyses to obtain area under the curve (AUC) values and to define optimal cutoff values to discriminate AD from pooled and individual non-AD groups. ROC curve analyses were only performed on biomarkers and ratios that differed significantly between the groups. Pairwise comparison of AUC values was performed by means of DeLong tests. The A?1-42/P-tau181P ratio (AUC?=?0.770) performed significantly better than A?1-42 (AUC?=?0.677, P?=?0.004), T-tau (AUC?=?0.592, P?

  10. Cerebrospinal fluid peptides as potential Parkinson disease biomarkers: a staged pipeline for discovery and validation.

    PubMed

    Shi, Min; Movius, James; Dator, Romel; Aro, Patrick; Zhao, Yanchun; Pan, Catherine; Lin, Xiangmin; Bammler, Theo K; Stewart, Tessandra; Zabetian, Cyrus P; Peskind, Elaine R; Hu, Shu-Ching; Quinn, Joseph F; Galasko, Douglas R; Zhang, Jing

    2015-03-01

    Finding robust biomarkers for Parkinson disease (PD) is currently hampered by inherent technical limitations associated with imaging or antibody-based protein assays. To circumvent the challenges, we adapted a staged pipeline, starting from our previous proteomic profiling followed by high-throughput targeted mass spectrometry (MS), to identify peptides in human cerebrospinal fluid (CSF) for PD diagnosis and disease severity correlation. In this multicenter study consisting of training and validation sets, a total of 178 subjects were randomly selected from a retrospective cohort, matching age and sex between PD patients, healthy controls, and neurological controls with Alzheimer disease (AD). From ?14,000 unique peptides displaying differences between PD and healthy control in proteomic investigations, 126 peptides were selected based on relevance and observability in CSF using bioinformatic analysis and MS screening, and then quantified by highly accurate and sensitive selected reaction monitoring (SRM) in the CSF of 30 PD patients versus 30 healthy controls (training set), followed by diagnostic (receiver operating characteristics) and disease severity correlation analyses. The most promising candidates were further tested in an independent cohort of 40 PD patients, 38 AD patients, and 40 healthy controls (validation set). A panel of five peptides (derived from SPP1, LRP1, CSF1R, EPHA4, and TIMP1) was identified to provide an area under curve (AUC) of 0.873 (sensitivity = 76.7%, specificity = 80.0%) for PD versus healthy controls in the training set. The performance was essentially confirmed in the validation set (AUC = 0.853, sensitivity = 82.5%, specificity = 82.5%). Additionally, this panel could also differentiate the PD and AD groups (AUC = 0.990, sensitivity = 95.0%, specificity = 97.4%). Furthermore, a combination of two peptides belonging to proteins TIMP1 and APLP1 significantly correlated with disease severity as determined by the Unified Parkinson's Disease Rating Scale motor scores in both the training (r = 0.381, p = 0.038)j and the validation (r = 0.339, p = 0.032) sets. The novel panel of CSF peptides, if validated in independent cohorts, could be used to assist in clinical diagnosis of PD and has the potential to help monitoring or predicting disease progression. PMID:25556233

  11. Cerebrospinal fluid proteins and free amino acids in patients with solvent induced chronic toxic encephalopathy and healthy controls.

    PubMed Central

    Moen, B E; Kyvik, K R; Engelsen, B A; Riise, T

    1990-01-01

    The concentrations of protein, albumin, IgG, and free amino acids in the cerebrospinal fluid of 16 patients with chronic toxic encephalopathy due to organic solvents were measured. The patient group consisted of all patients with this diagnosis in a neurological department in 1985. The diagnosis was based on neuraesthenic symptoms, pathological psychometric performance, and verified exposure to neurotoxic organic solvents. A control group of 16 patients with myalgias or backache, or both, and no signs of disease was used for comparison. The purpose was to study possible changes in the cerebrospinal fluid that might contribute to understanding the aetiology of solvent induced chronic toxic encephalopathy. A rise in protein, albumin, and IgG was found in the patient group compared with the control group, as well as reduced concentrations of phosphoethanolamine, taurine, homocarnosine, ethanolamine, alpha-aminobutyric acid, and leucine. Using a stepwise multiple regression analysis, taurine was negatively correlated to exposure to solvents. These findings may indicate membrane alterations in the central nervous system related to exposure to organic solvents. PMID:2337535

  12. Chronic changes in cerebrospinal fluid pathways produced by subarachnoid kaolin injection and experimental spinal cord trauma in the rabbit: their relationship with the development of spinal deformity

    Microsoft Academic Search

    Mehmet Turgut; Emre Çullu; Ay?egül Uysal; Mine Ertem Yurtseven; Bülent Alparslan

    2005-01-01

    Post-traumatic cystic changes in cerebrospinal fluid (CSF) pathways such as ventriculomegaly and\\/or hydrosyringomyelia are not uncommon, but their characteristics have not yet been fully clarified. This study was designed to investigate the alterations affecting the CSF pathways in rabbits at a late stage, and to clarify the relationship between these changes and the development of spinal deformity. In this study,

  13. Unchanged levels of interleukins, neopterin, interferon-gamma and tumor necrosis factor-alpha in cerebrospinal fluid of patients with dementia of the Alzheimer type.

    PubMed

    Engelborghs, S; De Brabander, M; De Crée, J; D'Hooge, R; Geerts, H; Verhaegen, H; De Deyn, P P

    1999-06-01

    Several histopathological studies suggest that amyloidogenesis in dementia of the Alzheimer type is accompanied by activated glia and glia-derived cytokines, leading to chronic, self-propagating, cytokine-mediated molecular and cellular reactions. As studies regarding inflammatory changes in cerebrospinal fluid of patients with dementia of the Alzheimer type has been inconclusive, we set up a prospective study to assess cerebrospinal fluid levels of interleukin-1beta, interleukin-6, interleukin-10, interleukin-12, soluble interleukin-2 receptor, interferon-gamma, tumor necrosis factor-alpha and neopterin in 20 patients with dementia of the Alzheimer type and 20 age- and sex-matched controls. Comparing both groups, no significant differences in concentrations and specific activities could be revealed. An additional 22 patients were included to enlarge the study population. No statistically significant differences were shown comparing patients (n=42) with the control group (n=20). We conclude that the immune-mediated inflammatory changes found in histopathological studies are not reflected in cerebrospinal fluid of patients with dementia of the Alzheimer type. Probably, cytokine production appears very localized in the central nervous system, not allowing representative detection in cerebrospinal fluid. Further studies assessing cytokine levels in various regions of central nervous system of patients with dementia of the Alzheimer type will be of interest to confirm this hypothesis. PMID:10402228

  14. Cerebrospinal Fluid Concentrations of Tryptophan and 5-Hydroxyindoleacetic Acid in Macaca Mulatta: Diurnal Variations and Response to Chronic Changes in Dietary Protein Intake

    Microsoft Academic Search

    Michael A. Grimes; Judy L. Cameron; John D. Fernstrom

    2000-01-01

    In rats, dietary protein is known to influence brain tryptophan (TRP) concentrations and serotonin (5HT) synthesis. However, few studies have examined this relationship in primates (including humans). We therefore studied the effect in monkeys of changes in chronic protein intake on plasma and cerebrospinal fluid (CSF) concentrations of TRP and 5-hydroxyindoleacetic acid (5HIAA), the principal 5HT metabolite. Juvenile male monkeys

  15. Glutamate levels in cerebrospinal fluid in amyotrophic lateral sclerosis: a reappraisal using a new HPLC method with coulometric detection in a large cohort of patients

    Microsoft Academic Search

    Odile Spreux-Varoquaux; Gilbert Bensimon; Lucette Lacomblez; François Salachas; Pierre François Pradat; Nadine Le Forestier; Abdellatif Marouan; Michel Dib; Vincent Meininger

    2002-01-01

    Glutamate is involved in the degeneration of motor neurons in amyotrophic lateral sclerosis (ALS). However, the aetiology of ALS appears heterogeneous, leading to the possibility that patient subgroups with different pathophysiology may exist. The concentration of glutamate in cerebrospinal fluid (CSF) is measured using a new HPLC method with coulometric detection in a large cohort of ALS patients and controls:

  16. The size of the intra- and extraventricular cerebrospinal fluid compartments in children with idiopathic benign widening of the frontal subarachnoid space

    Microsoft Academic Search

    P. Prassopoulos; D. Cavouras; S. Golfinopoulos; M. Nezi

    1995-01-01

    The aim of this study was to quantify the intra- and extraventricular cerebrospinal fluid (CSF) spaces in children with benign enlargement of the frontal subarachnoid space (BE). The infra-and supratentorial CSF compartments were measured in 61 CT examinations of children with BE, 3–27 months old, and compared with those of 96 CT examinations considered normal. Measurements of the ventricular system,

  17. The Stem Cell Marker Prominin-1\\/CD133 on Membrane Particles in Human Cerebrospinal Fluid Offers Novel Approaches for Studying Central Nervous System Disease

    Microsoft Academic Search

    Hagen B. Huttner; Peggy Janich; Martin Köhrmann; József Jászai; Florian Siebzehnrubl; Ingmar Blümcke; Meinolf Suttorp; Manfred Gahr; Daniela Kuhnt; Christopher Nimsky; Dietmar Krex; Gabriele Schackert; Kai Löwenbrück; Heinz Reichmann; Eric Jüttler; Werner Hacke; Peter D. Schellinger; Stefan Schwab; Michaela Wilsch-Bräuninger; Anne-Marie Marzesco; Denis Corbeil

    2008-01-01

    Cerebrospinal fluid (CSF) is routinely used for diagnosing and monitoring neurological diseases. The CSF proteins used so far for diagnostic purposes (except for those associ- ated with whole cells) are soluble. Here, we show that human CSF contains specific membrane particles that carry promi- nin-1\\/CD133, a neural stem cell marker implicated in brain tumors, notably glioblastoma. Differential and equilibrium centrifugation

  18. Receptor revision and atypical mutational characteristics in clonally expanded B cells from the cerebrospinal fluid of recently diagnosed multiple sclerosis patients

    Microsoft Academic Search

    Nancy L. Monson; Hans-Peter Brezinschek; Ruth I. Brezinschek; Angela Mobley; Gwen K. Vaughan; Elliot M. Frohman; Michael K. Racke; Peter E. Lipsky

    2005-01-01

    Purpose: to determine whether cerebrospinal fluid (CSF) B cells exhibit clonal expansion in patients recently diagnosed with multiple sclerosis (MS). CSF B cell clonal expansion was detected early in the disease process. Evidence of receptor revision was present in at least one MS patient who had been recently diagnosed with MS. Targeting of mutations to RGYW\\/WRCY motifs within CDRs was

  19. Changes in dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in human cerebrospinal fluid after L-dopa and deprenyl administration

    Microsoft Academic Search

    Krisztina Baraczka; M. I. K. Fekete; B. Kanyicska

    1983-01-01

    Summary The dopamine (DA) and DOPAC levels were measured in cerebrospinal fluid (CSF) using a radioenzymatic method. The influence of a specific monoamine oxidase B inhibitor (deprenyl) on changes in DA and DOPAC levels was studied in untreated patients or after L-dopa administration. A single dose of deprenyl alone did not change the CSF DA and DOPAC levels, a three

  20. Excitatory amino acid concentrations in ventricular cerebrospinal fluid after severe traumatic brain injury in infants and children: The role of child abuse

    Microsoft Academic Search

    Randall A. Ruppel; Patrick M. Kochanek; P. David Adelson; Marie E. Rose; Stephen R. Wisniewski; Michael J. Bell; Robert S. B. Clark; Donald W. Marion; Steven H. Graham

    2001-01-01

    Background: Excitotoxicity is an important mechanism in secondary neuronal injury after traumatic brain injury (TBI). Excitatory amino acids (EAAs) are increased in cerebrospinal fluid (CSF) in adults after TBI; however, studies in pediatric head trauma are lacking. We hypothesized that CSF glutamate, aspartate, and glycine would be increased after TBI in children and that these increases would be associated with

  1. Middle cerebral artery territory infarct due to Cryptococcus infectionstitle: An uncommon indication for cerebrospinal fluid analysis in stroke patients.

    PubMed

    Cachia, David; Singh, Charanjeet; Tetzlaff, Michael T; Penas-Prado, Marta

    2015-08-01

    Cryptococcal meningitis is the most common manifestation of cryptococcosis and is caused by the encapsulated yeast organism Cryptococcus neoformans. It occurs most commonly in patients with impaired cell-mediated immunity such as in HIV infection; patients with hematological malignancies; patients post solid-organ transplantation; on chronic steroids or immunosuppressants. Clinically, stroke can arise as a complication of cryptococcal meningitis. While cerebrospinal fluid (CSF) examination is usually not indicated for evaluation of stroke patients, demonstration of cryptococcal yeast forms in CSF is valuable in guiding appropriate therapy in arterial stroke caused by Cryptococci. Herein, we describe the CSF and radiologic correlation in a female patient who presented with disseminated cryptococcosis, cryptococcal meninigitis and a middle cerebral artery infarct. Diagn. Cytopathol. 2015;43:632-634. © 2014 Wiley Periodicals, Inc. PMID:25352313

  2. Radionuclide cisternography in detecting cerebrospinal fluid leak in spontaneous intracranial hypotension: a series of four case reports.

    PubMed

    Thomas, Damita L; Menda, Yusuf; Graham, Michael M

    2009-07-01

    Spontaneous intracranial hypotension (SIH) is an infrequent clinical entity characterized by cerebrospinal fluid (CSF) hypovolemia due to a CSF leak. The cause of the leak in SIH, however, is largely unknown, though structural meningeal weakness and mechanical stress factors have been postulated. Patients with SIH typically present with postural headaches, and occasionally with other symptomology as well, such as nausea, emesis, neck stiffness, and photophobia. In this case series, we present 4 patients who underwent radionuclide cisternography (RNC) for suspected CSF leak. All patients underwent RNC and MR and/or CT for evaluation. We found that RNC accurately detected and localized a CSF abnormality in all 4 patients, with each patient experiencing symptomatic relief following directed epidural blood patch. PMID:19542942

  3. L-thyroxine treatment and neurotransmitter levels in the cerebrospinal fluid of hypothyroid patients: a pilot study.

    PubMed

    Sjöberg, S; Eriksson, M; Nordin, C

    1998-11-01

    Monoamine precursors, neurotransmitters and their metabolites were studied in cerebrospinal fluid (CSF) obtained from nine newly diagnosed hypothyroid patients. Before treatment, the serum TSH correlated positively with the CSF concentrations of tyrosine and phenylalanine. During treatment, the levels of the precursors tryptophan, phenylalanine and tyrosine decreased significantly, as was also the case with dopamine and the noradrenaline metabolite 4-hydroxy-3-methoxyphenylglycol (HMPG), but not with serotonin, noradrenaline and the serotonin metabolite 5-hydroxyindoleacetic acid, nor the dopamine metabolites homovanilic acid and dihydroxyphenylacetic acid. The study provided some indication that the CSF levels of phenylalanine and tyrosine are related to thyroid function. Furthermore, we have found an indication that L-thyroxine treatment affects the CSF levels of the precursors as well as dopamine and HMPG. Our results support the notion that there is an interaction between thyroid function and CSF disposition of monoamine compounds. PMID:9849813

  4. Cerebrospinal fluid and serum prealbumin (transthyretin) in patients with multiple sclerosis (MS): comparison of particular subgroups of MS patients.

    PubMed

    Hybelová, M; Svatonová, J; Sobek, O; Adam, P; Dolezil, D; Adam, D

    2009-01-01

    The levels of prealbumin (PAB, transthyretin) were determined and evaluated in the cerebrospinal fluid (CSF) and serum in various subgroups of the multiple sclerosis (MS) patients. In severely disabled patients, serum PAB was elevated more frequently. CSF and serum PAB concentrations were higher in treated than in nontreated patients; the values above the upper reference limits were also more frequently found in treated patients. PAB index showed a tendency to decrease during the course of the disease. The routine determination of PAB in CSF and serum is, therefore, recommended to be recognized in MS patients as a substantial clinical value and, thus, be comprised, including also immunoglobulins and other parameters, into the spectrum of characteristics in Protein Panel. PMID:19418258

  5. Changes in Protein Level in the Cerebrospinal Fluid of a Patient with Cerebral Radiation Necrosis Treated with Bevacizumab

    PubMed Central

    Yano, Hirohito; Nakayama, Noriyuki; Morimitsu, Kasumi; Futamura, Manabu; Ohe, Naoyuki; Miwa, Kazuhiro; Shinoda, Jun; Iwama, Toru

    2014-01-01

    A 32-year-old woman underwent surgeries and radiation therapy for astrocytoma. She developed symptomatic radiation necrosis in the lesion, which caused hydrocephalus. She initially underwent ventricular drainage, because the protein level in the cerebrospinal fluid (CSF) was 787 mg/dL, which was too high for shunt surgery. Because she also had breast cancer, which was pathologically diagnosed as an invasive ductal carcinoma, standard bevacizumab therapy in combination with paclitaxel every 2 weeks was selected. Interestingly, after 2 days, the agents had dramatically reduced the CSF protein level. However, it returned to approximately the initial level within 2 weeks. After two courses of this regimen, a ventriculoperitoneal shunt was placed. After 10 courses of this regimen, the CSF protein level decreased to 338 mg/dL, which is less than half of the initial level. Long-term administration of bevacizumab might decrease leakage of protein from the vessels around the ventriculus. PMID:25574147

  6. Effects of natalizumab on oligoclonal bands in the cerebrospinal fluid of multiple sclerosis patients: a longitudinal study.

    PubMed

    Mancuso, R; Franciotta, D; Rovaris, M; Caputo, D; Sala, A; Hernis, A; Agostini, S; Calvo, Mg; Clerici, M

    2014-12-01

    Retrospective studies show that natalizumab modifies oligoclonal immunoglobulin (IgG) bands (OCBs) in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. In this study, we prospectively analyzed both serum and CSF samples from 24 MS patients, before and after 2 years of natalizumab-based therapy. Our results showed complete (55%) or partial (27%) disappearance of the OCBs in CSF samples that were taken after 2 years of therapy. Intrathecal IgG production, represented by the IgG index and IgGLoc, was also quantitatively reduced. Our data showed that natalizumab substantially modulates both intrathecal polyclonal and oligoclonal IgG production: This effect was much more potent than was previously reported. PMID:24948690

  7. Tumour necrosis factor alpha is elevated in serum and cerebrospinal fluid in multiple sclerosis and inflammatory neuropathies.

    PubMed

    Rentzos, M; Nikolaou, C; Rombos, A; Voumvourakis, K; Segditsa, I; Papageorgiou, C

    1996-02-01

    Tumour necrosis factor alpha (TNFalpha) is a peptide that is derived from T lymphocytes and macrophages and is used as a marker of activated cellular immune responses. TNFalpha was measured in paired sera and cerebrospinal fluid (CSF) from 30 patients with multiple sclerosis (MS) with worsening disability, 54 patients with other neurological diseases, and 20 normal subjects. A sensitive enzyme-linked immunosorbent assay was used to determine the TNFalpha levels. We found significantly elevated serum and CSF levels in 12 (40%) and 6 (20%) MS patients, respectively, compared with healthy controls (P < 0.007 and P < 0.05). Among the 18 patients with neuropathy, we also found high serum and CSF TNFalpha values in 3 (17%) and 5 (28%) patients, respectively (P < 0.04 and P < 0.002). Our study shows that TNFalpha is probably involved in the pathogenetic mechanisms of MS and other inflammatory neurological diseases. PMID:8750556

  8. Diagnosis of neuroschistosomiasis by antibody specificity index and semi-quantitative real-time PCR from cerebrospinal fluid and serum.

    PubMed

    Härter, Georg; Frickmann, Hagen; Zenk, Sebastian; Wichmann, Dominic; Ammann, Bettina; Kern, Peter; Fleischer, Bernhard; Tannich, Egbert; Poppert, Sven

    2014-02-01

    We describe the case of a 16-year-old German male expatriate from Ghana who presented with obstipation, dysuria, dysaesthesia of the gluteal region and the lower limbs, bilateral plantar hypaesthesia and paraesthesia without pareses. A serum-cerebrospinal fluid (CSF) Schistosoma spp. specific antibody specificity index of 3.1 was considered highly suggestive of intrathecal synthesis of anti-Schistosoma spp. specific antibodies, although standardization of this procedure has not previously been described. Diagnosis was confirmed by detection of Schistosoma DNA in CSF by semi-quantitative real-time PCR at 100-fold concentration compared with serum. Accordingly the two diagnostic procedures, which have not previously been applied for routine diagnosis, appear to be useful for the diagnosis of neuroschistosomiasis. Clinical symptoms resolved following anthelmintic and anti-inflammatory therapy. PMID:24227876

  9. Relation between plasmatic and cerebrospinal fluid oxidative stress biomarkers and intrathecal Ig synthesis in Multiple Sclerosis patients.

    PubMed

    Pasquali, Livia; Pecori, Chiara; Chico, Lucia; Iudice, Alfonso; Siciliano, Gabriele; Bonuccelli, Ubaldo

    2015-06-15

    The aim of this study was to evaluate if cerebrospinal fluid (CSF) oxidative stress biomarkers were related to plasmatic levels and to intrathecal Ig synthesis in 51 patients with Multiple Sclerosis (MS) or clinically isolated syndrome (CIS). Plasmatic and CSF ferric reducing ability (FRA) showed a significant positive correlation (? 0.28, p=0.04), while advanced oxidation protein products (AOPPs) did not. A negative correlation was found between IgG synthesis index and CSF FRA levels. No difference in CSF AOPPs or FRA was observed between patients with and without intrathecal IgM synthesis. Our results indicate that plasmatic and CSF FRA are strictly linked, while CSF oxidative stress biomarkers are not related to intrathecal Ig synthesis. PMID:26004154

  10. Evaluation of cerebrospinal fluid lactate and plasma lactate concentrations in anesthetized dogs with and without intracranial disease

    PubMed Central

    Caines, Deanne; Sinclair, Melissa; Wood, Darren; Valverde, Alexander; Dyson, Doris; Gaitero, Luis; Nykamp, Stephanie

    2013-01-01

    The objectives of this study were to establish a reference interval for canine cerebrospinal fluid lactate (CSFL) and to compare CSFL and plasma lactate (PL) concentrations in anesthetized dogs with and without intracranial disease. Using a prospective study, canine blood and cerebrospinal fluid were collected for lactate analysis in 11 dogs with intracranial disease after undergoing magnetic resonance imaging (MRI) (Group ID-MRI), in 10 healthy dogs post-MRI (Group H-MRI), and in 39 healthy dogs after induction of anesthesia (Group H-Sx). Dogs were anesthetized for the procedures using different anesthetic protocols. Neurological scores (NS) and sedation scores (SS) were assessed pre-anesthesia in ID-MRI dogs. The CSFL reference interval [90% confidence interval (CI) for lower and upper limits] was 1.1 (1.0 to 1.2) to 2.0 (2.0 to 2.1) mmol/L. Mean ± SD CSFL concentrations were: ID-MRI, 2.1 ± 0.8; H-MRI, 1.6 ± 0.4; and H-Sx, 1.6 ± 0.2 mmol/L. There was a tendency for higher CSFL in dogs in the ID-MRI group than in those in the H-MRI or H-Sx groups (P = 0.12). There was agreement between CSFL and PL in ID-MRI dogs (P = 0.007), but not in dogs in H-MRI (P = 0.5) or H-Sx (P = 0.2). Of the ID-MRI dogs, those with worse NS had higher CSFL (r2 = 0.44). The correlation between CSFL and PL in dogs with intracranial disease and between worse NS and higher CSFL warrants further investigation into the use of CSFL and PL for diagnostic and prognostic purposes. PMID:24124273

  11. Age-related changes in choroid plexus and blood-cerebrospinal fluid barrier function in the sheep.

    PubMed

    Chen, R L; Kassem, N A; Redzic, Z B; Chen, C P C; Segal, M B; Preston, J E

    2009-04-01

    Dysfunction of the choroid plexuses (CPs) and the blood-cerebrospinal fluid barrier (BCSFB) might contribute to age-related cognitive decline and neurodegenerative disease. We used the CPs from young (1-2 years), middle-aged (3-6 years) and old (7-10 years) sheep to explore effects of aging on various aspects of CP and BCSFB functions. Total protein in the cerebrospinal fluid (CSF) was significantly higher in old compared to young sheep and CSF secretion by the CP perfused in situ was significantly lower in both old and middle-aged when compared to young sheep, which correlated with reduced (22)Na(+) uptake and efflux by the CP. Steady-state extractions of a low and medium size molecular weight extracellular space marker, (14)C-mannitol and (3)H-polyethylene glycol, respectively, were significantly higher in CPs from old compared to young animals; however, there was no significant difference in steady-state extraction of a high molecular weight marker, (125)I-bovine serum albumin. This indicates increased passive BCSFB permeability for small and medium sized molecules in old sheep. CP redox activity was significantly lower in the old animals as assessed by the MTT assay, however, there was no significant difference in ATP content and energy charge of the CP with age suggesting adequate baseline energy reserve capacity. These data indicate that normal aging processes alter protein content in the CSF, CSF secretion, integrity of the BCSFB and Na(+) flux in the epithelial layer, which could impact on CSF homeostasis and turnover. PMID:19133323

  12. TRPV4 regulates the integrity of the blood-cerebrospinal fluid barrier and modulates transepithelial protein transport.

    PubMed

    Narita, Keishi; Sasamoto, Shohei; Koizumi, Schuichi; Okazaki, Shizuka; Nakamura, Hideki; Inoue, Takafumi; Takeda, Sen

    2015-06-01

    The diffusion of materials from systemic circulation to the central nervous system (CNS) is restricted by the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). Choroid plexus epithelial cells (CPECs) of the brain ventricles constitute the BCSFB and regulate the infiltration of plasma proteins as well as immune cells into the interstitium of the CNS. The barrier function is altered in pathologic conditions. However, the regulatory mechanism of BCSFB is not fully understood. Here, we investigated the function of transient receptor potential vanilloid 4 (TRPV4), a polymodally gated divalent cation channel that is highly expressed in CPECs. TRPV4 was localized broadly on the apical membrane in swine CPECs, in contrast with an intense ciliary localization found on other cell types. Treatment with the TRPV4-specific agonist, GSK1016790A (GSK; EC50 34 nM), induced a robust calcium influx and an immediate serine/threonine protein phosphorylation. The agonist treatment induced a marked decrease in the amount of filamentous actin and disintegrated the cell junctions in 10-20 minutes. In contrast, inhibition of the basal TRPV4 activity with the TRPV4-specific antagonist, HC067047 (HC; IC50 74 nM), reduced the basolateral-to-apical transport of ?-2-macroglobulin (A2M). Overall, this study demonstrated a novel physiologic function of TRPV4 in the regulation of BCSFB permeability.-Narita, K., Sasamoto, S., Koizumi, S., Okazaki, S., Nakamura, H., Inoue, T., Takeda, S. TRPV4 regulates the integrity of the blood-cerebrospinal fluid barrier and modulates transepithelial protein transport. PMID:25681460

  13. The Influence of Body Position on Cerebrospinal Fluid Pressure Gradient and Movement in Cats with Normal and Impaired Craniospinal Communication

    PubMed Central

    Radoš, Milan; Erceg, Gorislav; Petoši?, Antonio; Jurjevi?, Ivana

    2014-01-01

    Intracranial hypertension is a severe therapeutic problem, as there is insufficient knowledge about the physiology of cerebrospinal fluid (CSF) pressure. In this paper a new CSF pressure regulation hypothesis is proposed. According to this hypothesis, the CSF pressure depends on the laws of fluid mechanics and on the anatomical characteristics inside the cranial and spinal space, and not, as is today generally believed, on CSF secretion, circulation and absorption. The volume and pressure changes in the newly developed CSF model, which by its anatomical dimensions and basic biophysical features imitates the craniospinal system in cats, are compared to those obtained on cats with and without the blockade of craniospinal communication in different body positions. During verticalization, a long-lasting occurrence of negative CSF pressure inside the cranium in animals with normal cranio-spinal communication was observed. CSF pressure gradients change depending on the body position, but those gradients do not enable unidirectional CSF circulation from the hypothetical site of secretion to the site of absorption in any of them. Thus, our results indicate the existence of new physiological/pathophysiological correlations between intracranial fluids, which opens up the possibility of new therapeutic approaches to intracranial hypertension. PMID:24748150

  14. The influence of body position on cerebrospinal fluid pressure gradient and movement in cats with normal and impaired craniospinal communication.

    PubMed

    Klarica, Marijan; Radoš, Milan; Erceg, Gorislav; Petoši?, Antonio; Jurjevi?, Ivana; Oreškovi?, Darko

    2014-01-01

    Intracranial hypertension is a severe therapeutic problem, as there is insufficient knowledge about the physiology of cerebrospinal fluid (CSF) pressure. In this paper a new CSF pressure regulation hypothesis is proposed. According to this hypothesis, the CSF pressure depends on the laws of fluid mechanics and on the anatomical characteristics inside the cranial and spinal space, and not, as is today generally believed, on CSF secretion, circulation and absorption. The volume and pressure changes in the newly developed CSF model, which by its anatomical dimensions and basic biophysical features imitates the craniospinal system in cats, are compared to those obtained on cats with and without the blockade of craniospinal communication in different body positions. During verticalization, a long-lasting occurrence of negative CSF pressure inside the cranium in animals with normal cranio-spinal communication was observed. CSF pressure gradients change depending on the body position, but those gradients do not enable unidirectional CSF circulation from the hypothetical site of secretion to the site of absorption in any of them. Thus, our results indicate the existence of new physiological/pathophysiological correlations between intracranial fluids, which opens up the possibility of new therapeutic approaches to intracranial hypertension. PMID:24748150

  15. An integrated mechanism of pediatric pseudotumor cerebri syndrome: evidence of bioenergetic and hormonal regulation of cerebrospinal fluid dynamics.

    PubMed

    Sheldon, Claire A; Kwon, Young Joon; Liu, Grant T; McCormack, Shana E

    2015-02-01

    Pseudotumor cerebri syndrome (PTCS) is defined by the presence of elevated intracranial pressure (ICP) in the setting of normal brain parenchyma and cerebrospinal fluid (CSF). Headache, vision changes, and papilledema are common presenting features. Up to 10% of appropriately treated patients may experience permanent visual loss. The mechanism(s) underlying PTCS is unknown. PTCS occurs in association with a variety of conditions, including kidney disease, obesity, and adrenal insufficiency, suggesting endocrine and/or metabolic derangements may occur. Recent studies suggest that fluid and electrolyte balance in renal epithelia is regulated by a complex interaction of metabolic and hormonal factors; these cells share many of the same features as the choroid plexus cells in the central nervous system (CNS) responsible for regulation of CSF dynamics. Thus, we posit that similar factors may influence CSF dynamics in both types of fluid-sensitive tissues. Specifically, we hypothesize that, in patients with PTCS, mitochondrial metabolites (glutamate, succinate) and steroid hormones (cortisol, aldosterone) regulate CSF production and/or absorption. In this integrated mechanism review, we consider the clinical and molecular evidence for each metabolite and hormone in turn. We illustrate how related intracellular signaling cascades may converge in the choroid plexus, drawing on evidence from functionally similar tissues. PMID:25420176

  16. In-depth Exploration of Cerebrospinal Fluid by Combining Peptide Ligand Library Treatment and Label-free Protein Quantification*

    PubMed Central

    Mouton-Barbosa, Emmanuelle; Roux-Dalvai, Florence; Bouyssié, David; Berger, François; Schmidt, Eric; Righetti, Pier Giorgio; Guerrier, Luc; Boschetti, Egisto; Burlet-Schiltz, Odile; Monsarrat, Bernard; Gonzalez de Peredo, Anne

    2010-01-01

    Cerebrospinal fluid (CSF) is the biological fluid in closest contact with the brain and thus contains proteins of neural cell origin. Hence, CSF is a biochemical window into the brain and is particularly attractive for the search for biomarkers of neurological diseases. However, as in the case of other biological fluids, one of the main analytical challenges in proteomic characterization of the CSF is the very wide concentration range of proteins, largely exceeding the dynamic range of current analytical approaches. Here, we used the combinatorial peptide ligand library technology (ProteoMiner) to reduce the dynamic range of protein concentration in CSF and unmask previously undetected proteins by nano-LC-MS/MS analysis on an LTQ-Orbitrap mass spectrometer. This method was first applied on a large pool of CSF from different sources with the aim to better characterize the protein content of this fluid, especially for the low abundance components. We were able to identify 1212 proteins in CSF, and among these, 745 were only detected after peptide library treatment. However, additional difficulties for clinical studies of CSF are the low protein concentration of this fluid and the low volumes typically obtained after lumbar puncture, precluding the conventional use of ProteoMiner with large volume columns for treatment of patient samples. The method has thus been optimized to be compatible with low volume samples. We could show that the treatment is still efficient with this miniaturized protocol and that the dynamic range of protein concentration is actually reduced even with small amounts of beads, leading to an increase of more than 100% of the number of identified proteins in one LC-MS/MS run. Moreover, using a dedicated bioinformatics analytical work flow, we found that the method is reproducible and applicable for label-free quantification of series of samples processed in parallel. PMID:20093276

  17. Extracellular chaperones modulate the effects of Alzheimer’s patient cerebrospinal fluid on A?1-42 toxicity and uptake

    PubMed Central

    Wilson, Mark R.

    2009-01-01

    Alzheimer’s disease is characterised by the inappropriate death of brain cells and accumulation of the A? peptide in the brain. Thus, it is possible that there are fundamental differences between Alzheimer’s disease patients and healthy individuals in their abilities to clear A? from brain fluid and to protect neurons from A? toxicity. In the present study, we examined (1) the cytotoxicity of Alzheimer’s disease cerebrospinal fluid (CSF) compared to control CSF, (2) the ability of Alzheimer’s disease and control CSF to protect cells from A? toxicity and to promote cell-mediated clearance of A? and lastly (3) the effects of extracellular chaperones, normally found in CSF, on these processes. We show that the Alzheimer’s disease CSF samples tested were more toxic to cultured neuroblastoma cells than normal CSF. In addition, the Alzheimer’s disease CSF samples tested were less able to protect cells from A?-induced toxicity and less efficient at promoting macrophage-like cell uptake when compared to normal CSF. The addition of physiologically relevant concentrations of the extracellular chaperones, clusterin, haptoglobin and ?2-macroglobulin into CSF protected neuroblastoma cells from ??1-42 toxicity and promoted ??1-42 uptake in macrophage-like cells. These results suggest that extracellular chaperones are an important element of a system of extracellular protein folding quality control that protects against A? toxicity and accumulation. PMID:19472074

  18. Genes involved in cerebrospinal fluid production as candidate genes for late-onset Alzheimer's disease: a hypothesis.

    PubMed

    Wostyn, Peter; van Dam, Debby; Audenaert, Kurt; de Deyn, Peter Paul

    2011-12-01

    In rare patients with autosomal dominant, early-onset Alzheimer's disease (AD), pathogenic mutations in the genes encoding ?-amyloid precursor protein, and the ?-secretase-complex components presenilin-1 and presenilin-2 appear to result in ?-amyloid (A?) overproduction. The pathological accumulation of A? in the far more common late-onset AD is more likely to be the result of deficient clearance of A?. There is evidence that production and turnover of cerebrospinal fluid (CSF) help to clear toxic molecules such as A? from the interstitial fluid space of the brain to the bloodstream. CSF production and turnover have been shown to be decreased in aging and in pathological conditions, such as normal pressure hydrocephalus and AD. Reduced formation of CSF, with diminished clearance of A?, may play an important role in the onset and progression of AD. If reduced CSF turnover is a risk factor for AD, then its incidence ought to be increased under conditions of CSF circulatory failure. In this paper, the authors hypothesize that genes and variations of genes involved in the CSF production and absorption may contribute to the pathogenesis of late-onset AD. PMID:22023247

  19. Application of an improved biuret method to the determination of total protein in urine and cerebrospinal fluid without concentration step by use of Hitachi 7170 auto-analyzer.

    PubMed

    Guobing, X; Lili, J; Lihua, Z; Tiean, X

    2001-01-01

    A biuret automated colorimetric assay for total protein in urine and cerebrospinal fluids was established. The procedures were as follows. Acidify all urine sample before analysis. Add precipitant Na(2)WO(4) to urine samples. After 10 min, centrifuge, decant the supernatant fluid, drain the inverted tubes on absorbent tissue, dissolve the precipitation with 0.1 mol/L NaOH, and finally adapt the reconstituted urine to the Hitachi 7170 analyzer. A cell-free cerebrospinal fluid sample produced by centrifugation can be inserted in an auto-analyzer for protein measurement directly. The program: mix 35 microl sample (CSF or reconstituted urine) and standard with 0.2 mol/L NaOH; incurable at 37 degrees C for 5 min, and real A1. Add concentrated biuret reagent, and 10 min later measure absorbance A2 at 546 nm vs. reagent blank. Secondary wavelength was 700 nm. The test results were calculated against a one-point standard. This biuret colorimetric method was relatively simple, fast, and accurate for the determination of protein in urine and cerebrospinal fluid, with a wide linearity extending from 0.125 g/L up to 6 g/L, had a good correlation with Benzethonium chloride turbidimetry technique, and was a practical routine method. PMID:11436195

  20. Rapid and Sensitive RT-QuIC Detection of Human Creutzfeldt-Jakob Disease Using Cerebrospinal Fluid

    PubMed Central

    Orrú, Christina D.; Groveman, Bradley R.; Hughson, Andrew G.; Zanusso, Gianluigi; Coulthart, Michael B.

    2015-01-01

    ABSTRACT? Fast, definitive diagnosis of Creutzfeldt-Jakob disease (CJD) is important in assessing patient care options and transmission risks. Real-time quaking-induced conversion (RT-QuIC) assays of cerebrospinal fluid (CSF) and nasal-brushing specimens are valuable in distinguishing CJD from non-CJD conditions but have required 2.5 to 5 days. Here, an improved RT-QuIC assay is described which identified positive CSF samples within 4 to 14 h with better analytical sensitivity. Moreover, analysis of 11 CJD patients demonstrated that while 7 were RT-QuIC positive using the previous conditions, 10 were positive using the new assay. In these and further analyses, a total of 46 of 48 CSF samples from sporadic CJD patients were positive, while all 39 non-CJD patients were negative, giving 95.8% diagnostic sensitivity and 100% specificity. This second-generation RT-QuIC assay markedly improved the speed and sensitivity of detecting prion seeds in CSF specimens from CJD patients. This should enhance prospects for rapid and accurate ante mortem CJD diagnosis. Importance? A long-standing problem in dealing with various neurodegenerative protein misfolding diseases is early and accurate diagnosis. This issue is particularly important with human prion diseases, such as CJD, because prions are deadly, transmissible, and unusually resistant to decontamination. The recently developed RT-QuIC test allows for highly sensitive and specific detection of CJD in human cerebrospinal fluid and is being broadly implemented as a key diagnostic tool. However, as currently applied, RT-QuIC takes 2.5 to 5 days and misses 11 to 23% of CJD cases. Now, we have markedly improved RT-QuIC analysis of human CSF such that CJD and non-CJD patients can be discriminated in a matter of hours rather than days with enhanced sensitivity. These improvements should allow for much faster, more accurate, and practical testing for CJD. In broader terms, our study provides a prototype for tests for misfolded protein aggregates that cause many important amyloid diseases, such as Alzheimer’s, Parkinson’s, and tauopathies. PMID:25604790

  1. Effect of anatomical fine structure on the flow of cerebrospinal fluid in the spinal subarachnoid space.

    SciTech Connect

    Stockman, Harlan Wheelock

    2005-01-01

    The lattice Boltzmann method is used to model oscillatory flow in the spinal subarachnoid space. The effect of obstacles such as trabeculae, nerve bundles, and ligaments on fluid velocity profiles appears to be small, when the flow is averaged over the length of a vertebra. Averaged fluid flow in complex models is little different from flow in corresponding elliptical annular cavities. However, the obstacles stir the flow locally and may be more significant in studies of tracer dispersion.

  2. Large-scale clinical validation of a lateral flow immunoassay for detection of cryptococcal antigen in serum and cerebrospinal fluid specimens.

    PubMed

    Suwantarat, Nuntra; Dalton, Justin B; Lee, Richard; Green, Rachel; Memon, Warda; Carroll, Karen C; Riedel, Stefan; Zhang, Sean X

    2015-05-01

    We compared a lateral flow immunoassay (LFA) to a currently used enzyme immunoassay for detection of cryptococcal antigen in 396 sera and 651 cerebrospinal fluid specimens. We found 97% concordance between the 2 assays. The LFA detected an additional 22 positives. Overall, the LFA had sensitivity of 100% and specificity of 99.6% for the diagnosis of cryptococcosis. The LFA is rapid, accurate, and easy to perform, and it is suitable for routine patient care testing. PMID:25698631

  3. The Cerebrospinal Fluid Levels of Tau, Growth-Associated Protein43 and Soluble Amyloid Precursor Protein Correlate in Alzheimer’s Disease, Reflecting a Common Pathophysiological Process

    Microsoft Academic Search

    Magnus Sjögren; Pia Davidsson; Johan Gottfries; Hugo Vanderstichele; Åke Edman; Eugeen Vanmechelen; Anders Wallin; Kaj Blennow

    2001-01-01

    Cerebrospinal fluid (CSF) levels of tau (total tau), growth-associated protein-43 (GAP-43), soluble amyloid precursor protein (sAPP; i.e. total sAPP), and ?-amyloid42 (A?42) were studied in patients with frontotemporal dementia (FTD; n = 14), Alzheimer’s disease (AD; n = 47) and vascular dementia (VAD; n = 16), and in age-matched controls (n = 12). CSF-tau was increased in AD compared to

  4. Increased neuropeptide Y-like immunoreactivity in cerebrospinal fluid and plasma of human immunodeficiency virus-infected patients: relationship to HIV encephalopathy

    Microsoft Academic Search

    Rolf Malessa; Maja Heimbach; Norbert H. Brockmeyer; Ulrich Hengge; Wolfgang Rascher; Martin C. Michel

    1996-01-01

    Neuropeptide Y (NPY) is one of the most abundant and phylogenetically best conserved peptides in the mammalian central and peripheral nervous system where it plays an important role in the regulation of cardiovascular, metabolic, endocrine, immunological and cognitive functions. In a prospective study we determined neuropeptide Y-like immunoreactivity (NPY-LI) in cerebrospinal fluid (CSF) and plasma of 95 HIV-seropositive (n =

  5. Profiles of Extracellular miRNA in Cerebrospinal Fluid and Serum from Patients with Alzheimer's and Parkinson's Diseases Correlate with Disease Status and Features of Pathology

    PubMed Central

    Metpally, Raghu; Courtright, Amanda; Rakela, Benjamin; Beach, Thomas; Shill, Holly; Adler, Charles; Sabbagh, Marwan; Villa, Stephen; Tembe, Waibhav; Craig, David; Van Keuren-Jensen, Kendall

    2014-01-01

    The discovery and reliable detection of markers for neurodegenerative diseases have been complicated by the inaccessibility of the diseased tissue- such as the inability to biopsy or test tissue from the central nervous system directly. RNAs originating from hard to access tissues, such as neurons within the brain and spinal cord, have the potential to get to the periphery where they can be detected non-invasively. The formation and extracellular release of microvesicles and RNA binding proteins have been found to carry RNA from cells of the central nervous system to the periphery and protect the RNA from degradation. Extracellular miRNAs detectable in peripheral circulation can provide information about cellular changes associated with human health and disease. In order to associate miRNA signals present in cell-free peripheral biofluids with neurodegenerative disease status of patients with Alzheimer's and Parkinson's diseases, we assessed the miRNA content in cerebrospinal fluid and serum from postmortem subjects with full neuropathology evaluations. We profiled the miRNA content from 69 patients with Alzheimer's disease, 67 with Parkinson's disease and 78 neurologically normal controls using next generation small RNA sequencing (NGS). We report the average abundance of each detected miRNA in cerebrospinal fluid and in serum and describe 13 novel miRNAs that were identified. We correlated changes in miRNA expression with aspects of disease severity such as Braak stage, dementia status, plaque and tangle densities, and the presence and severity of Lewy body pathology. Many of the differentially expressed miRNAs detected in peripheral cell-free cerebrospinal fluid and serum were previously reported in the literature to be deregulated in brain tissue from patients with neurodegenerative disease. These data indicate that extracellular miRNAs detectable in the cerebrospinal fluid and serum are reflective of cell-based changes in pathology and can be used to assess disease progression and therapeutic efficacy. PMID:24797360

  6. Biological effect on blood cerebrospinal fluid barrier due to radio frequency electromagnetic fields exposure of the rat brain in vivo

    Microsoft Academic Search

    A. Ushiyama; H. Masuda; S. Hirota; K. Wake; H. Kawai; S. Watanabe; M. Taki; C. Ohkubo

    2007-01-01

    Concerns on health effects of radiofrequency (RF) signals have been discussed. Particularly, the effect on the central nerve\\u000a system is one of main interest among the general public. So far, there are lots of studies regarding the RF effect on the\\u000a Blood Brain Barrier (BBB), but no study of the RF effect on the Blood Cerebrospinal fluid Barrier (BCB). In

  7. Detection of RNA Sequences in Cultures of a Stealth Virus Isolated from the Cerebrospinal Fluid of a Health Care Worker with Chronic Fatigue Syndrome

    Microsoft Academic Search

    John Martin

    1997-01-01

    A cytopathic stealth virus was cultured from the cerebrospinal fluid of a nurse with chronic fatigue syndrome. Reverse transcriptase-polymerase chain reaction (RT-PCR) performed on the patient’s culture yielded positive results with primer sets based on sequences of a previously isolated African green monkey simian-cytomegalovirus-derived stealth virus. The same primer sets did not yield PCR products when tested directly on DNA

  8. Cerebrospinal fluid is an efficient route for establishing brain infection with feline immunodeficiency virus and transfering infectious virus to the periphery

    Microsoft Academic Search

    Pinghuang Liu; Lola C. Hudson; Mary B. Tompkins; Thomas W. Vahlenkamp; Brenda Colby; Cyndi Rundle; Rick B. Meeker

    2006-01-01

    Like human immunodeficiency virus (HIV), feline immunodeficiency virus (FIV) invades and infects the central nervous system\\u000a (CNS) soon after peripheral infection. The appearance of viral RNA is particularly prominent in the cerebrospinal fluid (CSF),\\u000a suggesting an efficient route of virus transfer across the blood-CSF barrier. This raises the concern whether this route can\\u000a establish a stable viral reservoir and also

  9. Effects of 2,4-dichlorophenoxyacetic acid (2,4-D) on biogenic amines and their acidic metabolites in brain and cerebrospinal fluid of rats

    Microsoft Academic Search

    Heikki A. Elo; Ewen MacDonald

    1989-01-01

    Effects of single subcutaneous doses of sodium 2,4-dichlorophenoxyacetate (2,4-D-Na) on biogenic amines and their acidic metabolites in rat brain and cerebrospinal fluid (CSF) were analyzed by high pressure liquid chromatography. After 200 mg\\/kg 2,4-D-Na, the cerebral concentration of 5-hydroxytryptamine (5-HT) was increased slightly and that of 5-hydroxyindoleacetic acid (5-HIAA) roughly 3-fold between 1 and 8 h after the administration. There

  10. Concentrations of indoleamine metabolic intermediates in the ventricular cerebrospinal fluid of advanced Parkinson's patients with severe postural instability and gait disorders

    Microsoft Academic Search

    R. P. Iacono; S. M. Kuniyoshi; J. R. Ahlman; G. J. Zimmerman; G. Maeda; R. D. Pearlstein

    1997-01-01

    Summary Postural instability and gait disorders (PIGD) are the primary causes of disability in many but not all advanced Parkinson's disease (PD) patients. We have measured the concentrations of serotonin, 5-hydroxytryptophan (5-HTP), 5-hydroxy-3-indoleacetic acid (5-HIAA), and homovanillic acid (HVA) in samples of ventricular cerebrospinal fluid from ten PD patients with severe disability from PIGD and from ten PD patients with

  11. Effects of Omega3 Fatty Acids on Inflammatory Markers in Cerebrospinal Fluid and Plasma in Alzheimer’s Disease: The OmegAD Study

    Microsoft Academic Search

    Yvonne Freund-Levi; Erik Hjorth; Catharina Lindberg; Tommy Cederholm; Gerd Faxen-Irving; Inger Vedin; Jan Palmblad; Lars-Olof Wahlund; Marianne Schultzberg; Hans Basun; Maria Eriksdotter Jönhagen

    2009-01-01

    Background: ?-3 fatty acids (?-3 FAs) found in dietary fish or fish oils are anti-inflammatory agents that may influence Alzheimer’s disease (AD). Objective: To study the effects of dietary ?-3 FA supplementation on inflammatory markers in cerebrospinal fluid (CSF) and plasma from patients with mild to moderate AD. Methods: Thirty-five patients (70.3 ± 8.2 years) were randomized to a daily

  12. Insulin-like growth factors and insulin-like growth factor binding proteins in cerebrospinal fluid and serum of patients with dementia of the Alzheimer type

    Microsoft Academic Search

    A. Tham; A. Nordberg; F. E. Grissom; C. Carlsson-Skwirut; M. Viitanen; V. R. Sara

    1993-01-01

    Summary  After acid gelchromatography cerebrospinal fluid and serum levels of immunoreactive insulin-like growth factor 1 and 2 (IGF-1 and IGF-2) were determined in patients with dementia of the Alzheimer type (AD) and in healthy subjects. The AD CSF levels of immunoreactive IGF-1 did not differ from the subjects but the levels of immunoreactive IGF-2 was significantly elevated in both serum and

  13. Implications of Vascular Endothelial Growth Factor, sFlt-1, and sTie-2 in Plasma, Serum and Cerebrospinal Fluid During Cerebral Ischemia in Man

    Microsoft Academic Search

    Kai-Michael Scheufler; Joachim Drevs; Vera van Velthoven; Petra Reusch; Joachim Klisch; Helmut G Augustin; Josef Zentner; Dieter Marme

    2003-01-01

    The relation between cerebral ischemia and local release of angiogenic factors was investigated after subarachnoid hemorrhage (SAH) in humans. Time-dependent concentration-changes of vascular endothelial growth factor (VEGF), sFlt-1 and sTie-2 extracted from plasma, serum, and cerebrospinal fluid (ventricular, cisternal, and lumbar) were analyzed in 15 patients surgically treated for ruptured aneurysms of the anterior circulation (Hunt and Hess grades I-V).

  14. Treatment of Growth Hormone-Deficient Adults with Recombinant Human Growth Hormone Increases the Concentration of Growth Hormone in the Cerebrospinal Fluid and Affects Neurotransmitters

    Microsoft Academic Search

    Jan-Ove Johansson; Göran Larson; Mats Andersson; Anders Elmgren; Lars Hynsjö; Anders Lindahl; Per-Arne Lundberg; Olle G. P. Isaksson; Sven Lindstedt; Bengt-Åke Bengtsson

    1995-01-01

    In a double-blind, placebo-controlled trial, the effects of recombinant human growth hormone were studied on cerebrospinal fluid concentrations of growth hormone, insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), monoamine metabolites, neuropeptides and endogenous opioid peptides. Twenty patients, 10 patients in each of 2 groups, with adult-onset, growth hormone deficiency were treated for 1 month with recombinant

  15. Choroid Plexus Epithelial Expression of MDR1 P Glycoprotein and Multidrug Resistance-Associated Protein Contribute to the Blood-Cerebrospinal-Fluid Drug-Permeability Barrier

    Microsoft Academic Search

    Vallabhaneni V. Rao; Julie L. Dahlheimer; Mark E. Bardgett; Abraham Z. Snyder; Rick A. Finch; Alan C. Sartorelli; David Piwnica-Worms

    1999-01-01

    The blood-brain barrier and a blood-cerebrospinal-fluid (CSF) barrier function together to isolate the brain from circulating drugs, toxins, and xenobiotics. The blood-CSF drug-permeability barrier is localized to the epithelium of the choroid plexus (CP). However, the molecular mechanisms regulating drug permeability across the CP epithelium are defined poorly. Herein, we describe a drug-permeability barrier in human and rodent CP mediated

  16. Preparation and application of a novel molecularly imprinted solid-phase microextraction monolith for selective enrichment of cholecystokinin neuropeptides in human cerebrospinal fluid.

    PubMed

    Ji, Xiang; Li, Dan; Li, Hua

    2015-08-01

    A novel molecularly imprinted polymer (MIP) monolith for highly selective extraction of cholecystokinin (CCK) neuropeptides was prepared in a micropipette tip. The MIPs were synthesized by epitope imprinting technique and the polymerization conditions were investigated and optimized. The synthesized MIPs were characterized by infrared spectroscopy, elemental analyzer and scanning electron microscope. A molecularly imprinted solid-phase microextraction (MI-?-SPE) method was developed for the extraction of CCK neuropeptides in aqueous solutions. The parameters affecting MI-?-SPE were optimized. The results indicated that this MIP monolith exhibited specific recognition capability and high enrichment efficiency for CCK neuropeptides. In addition, it showed excellent reusability. This MIP monolith was used for desalting and enrichment of CCK4, CCK5 and CCK8 from human cerebrospinal fluid prior to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis, and the results show that this MIP monolith can be a useful tool for effective purification and highly selective enrichment of multiple homologous CCK neuropeptides in cerebrospinal fluid simultaneously. By employing MI-?-SPE combined with HPLC-ESI-MS/MS analysis, endogenous CCK4 in human cerebrospinal fluid was quantified. Copyright © 2015 John Wiley & Sons, Ltd. PMID:25616243

  17. Comparative proteomics of cerebrospinal fluid reveals a predictive model for differential diagnosis of pneumococcal, meningococcal, and enteroviral meningitis, and novel putative therapeutic targets

    PubMed Central

    2015-01-01

    Background Meningitis is the inflammation of the meninges in response to infection or chemical agents. While aseptic meningitis, most frequently caused by enteroviruses, is usually benign with a self-limiting course, bacterial meningitis remains associated with high morbidity and mortality rates, despite advances in antimicrobial therapy and intensive care. Fast and accurate differential diagnosis is crucial for assertive choice of the appropriate therapeutic approach for each form of meningitis. Methods We used 2D-PAGE and mass spectrometry to identify the cerebrospinal fluid proteome specifically related to the host response to pneumococcal, meningococcal, and enteroviral meningitis. The disease-specific proteome signatures were inspected by pathway analysis. Results Unique cerebrospinal fluid proteome signatures were found to the three aetiological forms of meningitis investigated, and a qualitative predictive model with four protein markers was developed for the differential diagnosis of these diseases. Nevertheless, pathway analysis of the disease-specific proteomes unveiled that Kallikrein-kinin system may play a crucial role in the pathophysiological mechanisms leading to brain damage in bacterial meningitis. Proteins taking part in this cellular process are proposed as putative targets to novel adjunctive therapies. Conclusions Comparative proteomics of cerebrospinal fluid disclosed candidate biomarkers, which were combined in a qualitative and sequential predictive model with potential to improve the differential diagnosis of pneumococcal, meningococcal and enteroviral meningitis. Moreover, we present the first evidence of the possible implication of Kallikrein-kinin system in the pathophysiology of bacterial meningitis. PMID:26040285

  18. Direct analysis of clinical relevant single bacterial cells from cerebrospinal fluid during bacterial meningitis by means of micro-Raman spectroscopy.

    PubMed

    Harz, Michaela; Kiehntopf, Michael; Stöckel, Stephan; Rösch, Petra; Straube, Eberhard; Deufel, Thomas; Popp, Jürgen

    2009-02-01

    Bacterial meningitis is a relevant public health concern. Despite the availability of modern treatment strategies it is still a life-threatening disease that causes significant morbidity and mortality. Therefore, an initial treatment approach plays an important role. For in-time identification of specific bacterial pathogens of the cerebrospinal fluid (CSF) and emerged antimicrobial and adjunctive treatment, microbiological examination is of major importance. This contribution spotlights the potential of micro-Raman spectroscopy as a biomedical assay for direct analysis of bacteria in cerebrospinal fluid of patients with bacterial meningitis. The influence of miscellaneous artificial environments on several bacterial species present during bacterial meningitis was studied by means of Raman spectroscopy. The application of chemometric data interpretation via hierarchical cluster analysis (HCA) allows for the differentiation of in vitro cultured bacterial cells and can also be achieved on a single cell level. Moreover as proof of principle the investigation of a CSF sample obtained from a patient with meningococcal meningitis showed that the cerebrospinal fluid matrix does not mask the Raman spectrum of a bacterial cell notably since via chemometric analysis with HCA an identification of N. meningitidis cells from patients with bacterial meningitis could be achieved. PMID:19343686

  19. Primary Closure of a Cerebrospinal Fluid Fistula by Nonpenetrating Titanium Clips in Endoscopic Endonasal Transsphenoidal Surgery: Technical Note

    PubMed Central

    Kobayashi, Hiroyuki; Asaoka, Katsuyuki; Terasaka, Shunsuke; Murata, Jun-ich

    2010-01-01

    Postoperative cerebrospinal fluid (CSF) leakage is one of the most common and aggravating complications in transsphenoidal surgery. Although primary closure of the fistula would be the most desirable solution for an intraoperatively encountered CSF leak, it is difficult to achieve in such a deep and narrow operative field. In this article, the authors report endonasal endoscopic applications of no-penetrating titanium clips to repair a CSF fistula following tumor removal. The AnastoClip Vessel Closure System (VCS; LeMaitre Vascular, Boston, MA) was used for closure of a CSF fistula in endonasal transsphenoidal surgery. In all four patients, CSF leakage was successfully obliterated primarily with two to five clips. There was no postoperative CSF rhinorrhea or complications related to the use of the VCS. Metal artifact by the clips on postoperative images was tolerable. Primary closure of the fistula using the VCS was an effective strategy to prevent postoperative CSF leakage in transsphenoidal surgery. Future application can be expanded to reconstruction of the skull base dura via endonasal skull base approaches. PMID:22451799

  20. Chemotherapy-induced cerebrospinal fluid malabsorption in a shunted child: case report and review of the literature

    PubMed Central

    O'Halloran, Philip J; Kaliaperumal, Chandrasekaran; Caird, John

    2013-01-01

    Ventriculoperitoneal (VP) shunt insertion is one of the most common neurosurgical procedures for the treatment of chronic hydrocephalus. Although regarded as a relatively benign procedure, several complications including obstruction, infection and mechanical failure can be seen during the postoperative stage. Symptomatic sterile cerebrospinal fluid (CSF) ascites and hydrothoracies are rare complications of VP shunt surgery. The paucity of cases makes identifying the aetiological factors difficult, particularly without catheter tip migration. It is most likely that several factors interact to reduce the absorption of CSF. The authors discuss the case of a 5-year-old girl who developed CSF ascites and a pleural effusion after starting chemotherapy for a suprasellar pilocytic astrocytoma, 2?years post-VP shunt insertion, due to a secondary obstructive hydrocephalus. After the initial management of the presenting symptoms, the child's VP shunt was subsequently changed to a ventriculo-atrial shunt and the patient made an unremarkable recovery. We also review the literature pertaining to this rare complication, assessing identifiable risk factors and surgical management options. PMID:23396932

  1. Cerebrospinal fluid concentrations of vemurafenib in patients treated for brain metastatic BRAF-V600 mutated melanoma.

    PubMed

    Sakji-Dupré, Lilia; Le Rhun, Emilie; Templier, Carole; Desmedt, Eve; Blanchet, Benoit; Mortier, Laurent

    2015-08-01

    Anti-BRAF agents, including vemurafenib, have modified the prognosis for patients with melanoma. However, a difference can still be observed between extracerebral and cerebral responses. The aim of this study was to investigate the diffusion of vemurafenib in cerebrospinal fluid (CSF) from patients treated for brain metastatic BRAF-V600 mutated melanoma. Six patients treated with vemurafenib 960?mg twice daily were included. These patients had undergone a lumbar puncture because of suspicions of leptomeningeal metastasis, along with simultaneous blood sampling to measure vemurafenib level. The concentrations of vemurafenib in the CSF and the plasma were measured by high-performance liquid chromatography. The mean plasma and CSF concentrations of vemurafenib were 53.4±26.2 and 0.47±0.37?mg/l, respectively. The mean ratio of the CSF?:?plasma concentration was 0.98±0.84%. No relationship was found between plasma and CSF concentrations (P=0.8). In conclusion, our preliminary results highlight for the first time a low CSF vemurafenib penetration rate associated with a large interindividual variability in patients treated for metastatic BRAF-V600 mutated melanoma and brain metastases. Further investigations with larger cohorts are required to study the relationship between CSF vemurafenib concentrations and cerebral response. PMID:25933211

  2. Sustained Elevation of Kynurenic Acid in the Cerebrospinal Fluid of Patients with Herpes Simplex Virus Type 1 Encephalitis

    PubMed Central

    Atlas, Ann; Franzen-Röhl, Elisabeth; Söderlund, Johan; Jönsson, Erik G; Samuelsson, Martin; Schwieler, Lilly; Sköldenberg, Birgit; Engberg, Göran

    2013-01-01

    Herpes simplex virus (HSV) type 1 encephalitis (HSE) is a viral infectious disease with commonly occurring neurodegeneration and neurological/cognitive long-term sequelae. Kynurenic acid (KYNA) is a neuroactive tryptophan metabolite, which is elevated in the cerebrospinal fluid (CSF) during viral infection as a result of immune activation. The aim of the study was to investigate the role of endogenous brain KYNA for the long-term outcome of the disease. CSF KYNA concentration was analyzed in 25 HSE patients along the course of the disease and compared with that of 25 age-matched healthy volunteers. Within 3 weeks of admission CSF KYNA of HSE patients was markedly elevated (median 33.6 nM) compared to healthy volunteers (median 1.45 nM). Following a decline observed after 1–2 months, levels of CSF KYNA were elevated more than 1 year after admission (median 3.4 nM range: 1–9 years). A negative correlation was found between initial CSF KYNA concentrations and severity of the long-term sequelae. This study show a marked elevation in CSF KYNA from patients with HSE, most pronounced during the acute phase of the disease and slowly declining along the recovery. We propose that brain KYNA might potentially protect against neurodegeneration while causing a long-lasting loss in cognitive function associated with the disease. PMID:24324341

  3. Kinetics of T-cell-based assays on cerebrospinal fluid and peripheral blood mononuclear cells in patients with tuberculous meningitis

    PubMed Central

    Park, Ki-Ho; Lee, Mi Suk; Lee, Sang-Oh; Choi, Sang-Ho; Kim, Yang Soo; Woo, Jun Hee; Kang, Joong Koo; Lee, Sang-Ahm

    2014-01-01

    Background/Aims The goal of this study was to monitor tuberculosis (TB)-specific T-cell responses in cerebrospinal fluid-mononuclear cells (CSF-MCs) and peripheral blood mononuclear cells (PBMCs) in patients with tuberculous meningitis (TBM) over the course of anti-TB therapy. Methods Adult patients (? 16 years) with TBM admitted to Asan Medical Center, Seoul, South Korea, were prospectively enrolled between April 2008 and April 2011. Serial blood or CSF samples were collected over the course of the anti-TB therapy, and analyzed using an enzyme-linked immunosorbent spot (ELISPOT) assay. Results Serial ELISPOT assays were performed on PBMCs from 17 patients (seven definite, four probable, and six possible TBM) and CSF-MC from nine patients (all definite TBM). The median number of interferon-gamma (IFN-?)-producing T-cells steadily increased during the first 6 months after commencement of anti-TB therapy in PBMCs. Serial CSF-MC ELISPOT assays revealed significant variability in immune responses during the first 6 weeks of anti-TB therapy, though early increases in CSF-MC ELISPOT results were associated with treatment failure or paradoxical response. Conclusions Serial analysis of PBMCs by ELISPOT during the course of treatment was ineffective for predicting clinical response. However, increases in TB-specific IFN-?-producing T-cells in CSF-MC during the early phase of anti-TB therapy may be predictive of clinical failure. PMID:25378978

  4. Persistence of West Nile Virus (WNV) IgM antibodies in cerebrospinal fluid from patients with CNS disease.

    PubMed

    Kapoor, Hema; Signs, Kimberly; Somsel, Patricia; Downes, Frances P; Clark, Patricia A; Massey, Jeffrey P

    2004-12-01

    The Michigan Department of Community Health (MDCH) reported 644 laboratory positive human cases of West Nile Virus (WNV) in the 2002 outbreak in the US, of which 559 cases presented with either meningitis or encephalitis. The first line test utilized for diagnosis of WNV infection was the immunoglobulin M (IgM)-capture enzyme-linked immunosorbent assay (MAC-ELISA). We continued testing for WNV even during winter months of the year 2002-2003 due to the awareness of other modes of WNV transmission (blood transfusion, organ transplantation, transplacental, breast milk, and occupational) as well as concern for people traveling to endemic areas. As a result of year-round testing for WNV infections during 2002-2003, we detected WNV IgM-specific antibodies in cerebrospinal fluid (CSF) specimens from three patients persisting for 110, 141, and 199 days post acute phase infection in patients with central nervous system (CNS) disease. This is a new observation and there is no published data on the persistence of WNV IgM antibodies in CSF specimens beyond 47 days. Thus, it is important to note that the presence of WNV IgM class antibodies may not always reflect acute phase infection with this virus. PMID:15494271

  5. Assessment of free light chains in the cerebrospinal fluid of patients with lymphomatous meningitis – a pilot study

    PubMed Central

    Hildebrandt, B; Müller, C; Pezzutto, A; Daniel, PT; Dörken, B; Scholz, C

    2007-01-01

    Background Lymphomatous meningitis (LM) represents a severe complication of malignant lymphomas. While clinical suspicion is raised by symptoms ranging from mild disturbances of sensation to severe pain or impaired consciousness, the definite diagnosis of LM is often difficult to obtain. Since B-cell lymphomas are clonally restricted to express either kappa or lambda immunoglobulin light chain, we hypothesised that analysis of free light chain (FLC) ratios might facilitate the diagnosis of LM. Methods Kappa and lambda FLC were measured using a novel nephelometric assay in cerebrospinal fluid (CSF) and serum from 17 patients. 5/17 suffered from LM as demonstrated by cytology, immunocytology, and/or imaging procedures. Results Measurement of FLC concentrations in CSF was achieved for all 17 patients. FLC levels in CSF were lower than serum FLC levels in samples for the same patient obtained at the same time (p < 0.01). CSF and serum FLC concentrations correlated weakly in all patients irrespective of LM status. Significantly more patients with cytopathologically and immunohistochemically proven LM displayed abnormal kappa/lambda FLC ratios in CSF compared to individuals with no LM (p < 0.01). Conclusion This is the first report demonstrating that a significant proportion of LM patients display an abnormal kappa/lambda FLC ratio in the CSF. PMID:17915026

  6. Vitamin D Binding Protein Isoforms and Apolipoprotein E in Cerebrospinal Fluid as Prognostic Biomarkers of Multiple Sclerosis

    PubMed Central

    Lis, Katarzyna; Minari, Nicoletta; Falvo, Sara; Marnetto, Fabiana; Caldano, Marzia; Reviglione, Raffaella; Berchialla, Paola; Capobianco, Marco A.; Malentacchi, Maria; Corpillo, Davide; Bertolotto, Antonio

    2015-01-01

    Background Multiple sclerosis (MS) is a multifactorial autoimmune disease of the central nervous system with a heterogeneous and unpredictable course. To date there are no prognostic biomarkers even if they would be extremely useful for early patient intervention with personalized therapies. In this context, the analysis of inter-individual differences in cerebrospinal fluid (CSF) proteome may lead to the discovery of biological markers that are able to distinguish the various clinical forms at diagnosis. Methods To this aim, a two dimensional electrophoresis (2-DE) study was carried out on individual CSF samples from 24 untreated women who underwent lumbar puncture (LP) for suspected MS. The patients were clinically monitored for 5 years and then classified according to the degree of disease aggressiveness and the disease-modifying therapies prescribed during follow up. Results The hierarchical cluster analysis of 2-DE dataset revealed three protein spots which were identified by means of mass spectrometry as Apolipoprotein E (ApoE) and two isoforms of vitamin D binding protein (DBP). These three protein spots enabled us to subdivide the patients into subgroups correlated with clinical classification (MS aggressive forms identification: 80%). In particular, we observed an opposite trend of values for the two protein spots corresponding to different DBP isoforms suggesting a role of a post-translational modification rather than the total protein content in patient categorization. Conclusions These findings proved to be very interesting and innovative and may be developed as new candidate prognostic biomarkers of MS aggressiveness, if confirmed. PMID:26046356

  7. Laboratory diagnosis of central nervous system infections with herpes simplex virus by PCR performed with cerebrospinal fluid specimens.

    PubMed Central

    Mitchell, P S; Espy, M J; Smith, T F; Toal, D R; Rys, P N; Berbari, E F; Osmon, D R; Persing, D H

    1997-01-01

    Until recently, the laboratory diagnosis of central nervous system (CNS) infections with herpes simplex virus (HSV) has been limited by poor sensitivity and/or specificity. We assessed the diagnostic utility of PCR for detection of HSV in over 2,100 specimens referred to the Mayo Clinic from August 1993 to May 1996. DNA extracted from cerebrospinal fluid (CSF) samples with IsoQuick was amplified by PCR with oligonucleotide primers directed to the DNA polymerase gene of HSV, yielding a 290-bp amplicon. HSV DNA was detected in 150 (135 by gel electrophoresis, 15 by Southern blotting only) of 2,106 (7.1%) specimens. PCR-positive CNS disease occurred in patients ranging in age from 13 days to 89 years; 59% of the cases occurred in patients between the ages of 30 and 69, and 21 (14%) of the patients were infants. Genotype analysis was not routinely performed; however, amplification of a 335-bp product within the thymidine kinase gene of HSV revealed 13 positions within a span of 80 nucleotides that accurately identified the two serotypes of the virus according to 14 reference strains. We conclude that PCR detection of HSV DNA in CSF specimens should be considered an emerging "gold standard" for the laboratory diagnosis of CNS infections with this virus. PMID:9350750

  8. Kynurenic Acid Levels in Cerebrospinal Fluid from Patients with Alzheimer’s Disease or Dementia with Lewy Bodies

    PubMed Central

    Wennström, Malin; Nielsen, Henrietta M; Orhan, Funda; Londos, Elisabet; Minthon, Lennart; Erhardt, Sophie

    2014-01-01

    Kynurenic acid (KYNA) is implicated in cognitive functions. Altered concentrations of the compound are found in serum and cerebrospinal fluid (CSF) of patients with Alzheimer’s disease (AD). Further studies to determine whether KYNA serves as a biomarker for cognitive decline and dementia progression are required. In this study, we measured CSF KYNA levels in AD patients (n = 19), patients with dementia with Lewy bodies (DLB) (n = 18), and healthy age-matched controls (Ctrls)) (n = 20) to further explore possible correlations between KYNA levels, cognitive decline, and well-established AD and inflammatory markers. Neither DLB patients nor AD patients showed significantly altered CSF KYNA levels compared to Ctrls. However, female AD patients displayed significantly higher KYNA levels compared to male AD patients, a gender difference not seen in the Ctrl or DLB group. Levels of KYNA significantly correlated with the AD-biomarker P-tau and the inflammation marker soluble intercellular adhesion molecule-1 (sICAM-1) in the AD patient group. No associations between KYNA and cognitive functions were found. Our study shows that, although KYNA was not associated with cognitive decline in AD or DLB patients, it may be implicated in AD-related hyperphosphorylation of tau and inflammation. Further studies on larger patient cohorts are required to understand the potential role of KYNA in AD and DLB. PMID:24855376

  9. Photoacoustic and photothermal detection of circulating tumor cells, bacteria and nanoparticles in cerebrospinal fluid in vivo and ex vivo

    PubMed Central

    Nedosekin, Dmitry A.; Juratli, Mazen A.; Sarimollaoglu, Mustafa; Moore, Christopher L.; Rusch, Nancy J.; Smeltzer, Mark S.; Zharov, Vladimir P.; Galanzha, Ekaterina I.

    2014-01-01

    Circulating cells, proteins, microparticles, and DNA in cerebrospinal fluid (CSF) are excellent biomarkers of many diseases, including cancer and infections. However, the sensitivity of existing methods is limited in their ability to detect rare CSF biomarkers at the treatable, early-stage of diseases. Here, we introduce novel CSF tests based on in vivo multicolor photoacoustic flow cytometry (PAFC) and ex vivo photothermal scanning cytometry. In the CSF of tumor-bearing mice, we molecularly detected in vivo circulating tumor cells (CTCs) before the development of breast cancer brain metastasis with 20-times higher sensitivity than with current assays. For the first time, we demonstrated assessing three pathways (i.e., blood, lymphatic, and CSF) of CTC dissemination, tracking nanoparticles in CSF in vivo and their imaging ex vivo. In label-free CSF samples, we counted leukocytes, erythrocytes, melanoma cells, and bacteria and imaged intracellular cytochromes, hemoglobin, melanin, and carotenoids, respectively. Taking into account the safety of PAFC, its translation for use in humans is expected to improve disease diagnosis beyond conventional detection limits. PMID:23681943

  10. Serum uric acid levels and their correlation with clinical and cerebrospinal fluid parameters in patients with neuromyelitis optica.

    PubMed

    Liu, Caiyan; Xu, Yan; Cui, Liying; Wang, Jianming; Peng, Bin; Zhong, Lizhen; Chen, Xingwang

    2013-02-01

    Although uric acid (UA) concentration has been considered a surrogate marker for monitoring the progression of multiple sclerosis (MS), less is known about the relationship between UA and the progression of neuromyelitis optica (NMO). We therefore investigated the correlations between serum UA concentrations and the clinical and cerebrospinal fluid (CSF) parameters in patients with NMO. Factors assessed in patients with NMO included gender, disease duration, disease disability, CSF white blood cell (WBC) counts, oligoclonal bands (OB), 24 hour immunoglobulin (Ig)G index, and myelin basic protein (MBP) concentration. Mean serum UA concentrations were compared in patients with NMO and in a control group of patients with cerebral infarction (CI). We found that mean serum UA concentrations were significantly lower in patients with NMO compared to those with CI (206.81 compared to 274.00 ?mol/L, p=0.00). Serum UA concentration was correlated directly with NMO duration (p=0.013) and was inversely correlated with the Expanded Disability Status Scale score (p=0.021). Patients with NMO with lower serum UA concentrations tended to be positive for OB, to have higher CSF protein and MBP concentrations, and to have higher WBC counts and 24 hour IgG index, but no correlation was statistically significant. UA may be a useful surrogate marker for monitoring NMO activity. PMID:23164828

  11. Cerebrospinal fluid biochemical studies in patients with Parkinson's disease: toward a potential search for biomarkers for this disease

    PubMed Central

    Jiménez-Jiménez, Félix J.; Alonso-Navarro, Hortensia; García-Martín, Elena; Agúndez, José A. G.

    2014-01-01

    The blood-brain barrier supplies brain tissues with nutrients and filters certain compounds from the brain back to the bloodstream. In several neurodegenerative diseases, including Parkinson's disease (PD), there are disruptions of the blood-brain barrier. Cerebrospinal fluid (CSF) has been widely investigated in PD and in other parkinsonian syndromes with the aim of establishing useful biomarkers for an accurate differential diagnosis among these syndromes. This review article summarizes the studies reported on CSF levels of many potential biomarkers of PD. The most consistent findings are: (a) the possible role of CSF urate on the progression of the disease; (b) the possible relations of CSF total tau and phosphotau protein with the progression of PD and with the preservation of cognitive function in PD patients; (c) the possible value of CSF beta-amyloid 1-42 as a useful marker of further cognitive decline in PD patients, and (d) the potential usefulness of CSF neurofilament (NFL) protein levels in the differential diagnosis between PD and other parkinsonian syndromes. Future multicentric, longitudinal, prospective studies with long-term follow-up and neuropathological confirmation would be useful in establishing appropriate biomarkers for PD. PMID:25426023

  12. A validated LC-MS/MS assay for quantification of 24(S)-hydroxycholesterol in plasma and cerebrospinal fluid.

    PubMed

    Sidhu, Rohini; Jiang, Hui; Farhat, Nicole Y; Carrillo-Carrasco, Nuria; Woolery, Myra; Ottinger, Elizabeth; Porter, Forbes D; Schaffer, Jean E; Ory, Daniel S; Jiang, Xuntian

    2015-06-01

    24(S)-hydroxycholesterol [24(S)-HC] is a cholesterol metabolite that is formed almost exclusively in the brain. The concentrations of 24(S)-HC in cerebrospinal fluid (CSF) and/or plasma might be a sensitive marker of altered cholesterol metabolism in the CNS. A highly sensitive 2D-LC-MS/MS assay was developed for the quantification of 24(S)-HC in human plasma and CSF. In the development of an assay for 24(S)-HC in CSF, significant nonspecific binding of 24(S)-HC was observed and resolved with the addition of 2.5% 2-hydroxypropyl-?-cyclodextrin (HP-?-CD) into CSF samples. The sample preparation consists of liquid-liquid extraction with methyl-tert-butyl ether and derivatization with nicotinic acid. Good linearity was observed in a range from 1 to 200 ng/ml and from 0.025 to 5 ng/ml, for plasma and CSF, respectively. Acceptable precision and accuracy were obtained for concentrations over the calibration curve ranges. Stability of 24(S)-HC was reported under a variety of storage conditions. This method has been successfully applied to support a National Institutes of Health-sponsored clinical trial of HP-?-CD in Niemann-Pick type C1 patients, in which 24(S)-HC is used as a pharmacodynamic biomarker. PMID:25866316

  13. Tanycyte-like cells form a blood-cerebrospinal fluid barrier in the circumventricular organs of the mouse brain.

    PubMed

    Langlet, Fanny; Mullier, Amandine; Bouret, Sebastien G; Prevot, Vincent; Dehouck, Benedicte

    2013-10-15

    Tanycytes are highly specialized ependymal cells that form a blood-cerebrospinal fluid (CSF) barrier at the level of the median eminence (ME), a circumventricular organ (CVO) located in the tuberal region of the hypothalamus. This ependymal layer harbors well-organized tight junctions, a hallmark of central nervous system barriers that is lacking in the fenestrated portal vessels of the ME. The displacement of barrier properties from the vascular to the ventricular side allows the diffusion of blood-borne molecules into the parenchyma of the ME while tanycyte tight junctions control their diffusion into the CSF, thus maintaining brain homeostasis. In the present work, we combined immunohistochemical and permeability studies to investigate the presence of tanycyte barriers along the ventricular walls of other brain CVOs. Our data indicate that, unlike cuboidal ependymal cells, ependymal cells bordering the CVOs possess long processes that project into the parenchyma of the CVOs to reach the fenestrated capillary network. Remarkably, these tanycyte-like cells display well-organized tight junctions around their cell bodies. Consistent with these observations, permeability studies show that this ependymal layer acts as a diffusion barrier. Together, our results suggest that tanycytes are a characteristic feature of all CVOs and yield potential new insights into their involvement in regulating the exchange between the blood, the brain, and the CSF within these "brain windows." PMID:23649873

  14. Lipocalin-type prostaglandin D synthase scavenges biliverdin in the cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage.

    PubMed

    Inui, Takashi; Mase, Mitsuhito; Shirota, Ryoko; Nagashima, Mariko; Okada, Tetsuya; Urade, Yoshihiro

    2014-09-01

    Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is the second major protein in human cerebrospinal fluid (CSF) and belongs to the lipocalin superfamily composed of various secretory lipophilic ligand transporter proteins. However, the endogenous ligand of L-PGDS has not yet been elucidated. In this study, we purified L-PGDS from the CSF of aneurysmal subarachnoid hemorrhage (SAH) patients. Lipocalin-type PG D synthase showed absorbance spectra with major peaks at 280 and 392?nm and a minor peak at around 660?nm. The absorbance at 392?nm of L-PGDS increased from 1 to 9 days and almost disappeared at 2 months after SAH, whereas the L-PGDS activity decreased from 1 to 7 days and recovered to normal at 2 months after SAH. These results indicate that some chromophore had accumulated in the CSF after SAH and bound to L-PGDS, thus inactivating it. Matrix assisted laser desorption ionization time-of-flight mass spectrometry of L-PGDS after digestion of it with endoproteinase Lys-C revealed that L-PGDS had covalently bound biliverdin, a by-product of heme breakdown. These results suggest that L-PGDS acted as a scavenger of biliverdin, which is a molecule not found in normal CSF. This is the first report of identification of a pathophysiologically important endogenous ligand for this lipocalin superfamily protein in humans. PMID:25005874

  15. Proteomic analysis of cerebrospinal fluid before and after intrathecal injection of steroid into patients with postherpetic pain.

    PubMed

    Lu, Jingshan; Katano, Tayo; Nishimura, Wataru; Fujiwara, Shunsuke; Miyazaki, Shinichiro; Okasaki, Issay; Aritake, Kosuke; Urade, Yoshihiro; Minami, Toshiaki; Ito, Seiji

    2012-10-01

    Postherpetic neuralgia (PHN) is the most frequent complication of herpes zoster, and the risk of it increases with age. By comparing proteomes of the cerebrospinal fluid (CSF) before and after the treatment, it may be possible to identify proteins that play a role in PHN and to predict responses to various treatments. To address this issue, we enrolled eight outpatients with PHN over 55 years of age and treated them with intrathecal methylprednisolone and lidocaine four times every week, collecting CSF samples before the treatment at each visit. We used 2D DIGE to investigate differentially expressed proteins in the CSF before and after repetitive treatments individually. Of 145 differentially expressed spots, the levels of nine proteins were decreased by the treatment including lipocalin-type prostaglandin D synthase (L-PGDS), and five were increased by it. The time course of alterations in the L-PGDS concentration in the CSF of each patient, detected by a pairwise and sandwich ELISA by SPR constructed here was well correlated with that by 1DE Western blots with anti-L-PGDS antibody, but was not related with that of the pain relief. The present study demonstrates that the real-time ELISA was precise and sensitive enough to measure L-PGDS in the CSF and that the steroid treatment decreased the L-PGDS concentration in CSF. PMID:22936653

  16. Photoacoustic and photothermal detection of circulating tumor cells, bacteria and nanoparticles in cerebrospinal fluid in vivo and ex vivo.

    PubMed

    Nedosekin, Dmitry A; Juratli, Mazen A; Sarimollaoglu, Mustafa; Moore, Christopher L; Rusch, Nancy J; Smeltzer, Mark S; Zharov, Vladimir P; Galanzha, Ekaterina I

    2013-06-01

    Circulating cells, bacteria, proteins, microparticles, and DNA in cerebrospinal fluid (CSF) are excellent biomarkers of many diseases, including cancer and infections. However, the sensitivity of existing methods is limited in their ability to detect rare CSF biomarkers at the treatable, early-stage of diseases. Here, we introduce novel CSF tests based on in vivo photoacoustic flow cytometry (PAFC) and ex vivo photothermal scanning cytometry. In the CSF of tumor-bearing mice, we molecularly detected in vivo circulating tumor cells (CTCs) before the development of breast cancer brain metastasis with 20-times higher sensitivity than with current assays. For the first time, we demonstrated assessing three pathways (i.e., blood, lymphatic, and CSF) of CTC dissemination, tracking nanoparticles in CSF in vivo and their imaging ex vivo. In label-free CSF samples, we counted leukocytes, erythrocytes, melanoma cells, and bacteria and imaged intracellular cytochromes, hemoglobin, melanin, and carotenoids, respectively. Taking into account the safety of PAFC, its translation for use in humans is expected to improve disease diagnosis beyond conventional detection limits. PMID:23681943

  17. Tanycyte-Like Cells Form a Blood–Cerebrospinal Fluid Barrier in the Circumventricular Organs of the Mouse Brain

    PubMed Central

    Langlet, Fanny; Mullier, Amandine; Bouret, Sebastien G.; Prevot, Vincent; Dehouck, Benedicte

    2014-01-01

    Tanycytes are highly specialized ependymal cells that form a blood–cerebrospinal fluid (CSF) barrier at the level of the median eminence (ME), a circumventricular organ (CVO) located in the tuberal region of the hypothalamus. This ependymal layer harbors well-organized tight junctions, a hallmark of central nervous system barriers that is lacking in the fenestrated portal vessels of the ME. The displacement of barrier properties from the vascular to the ventricular side allows the diffusion of blood-borne molecules into the parenchyma of the ME while tanycyte tight junctions control their diffusion into the CSF, thus maintaining brain homeostasis. In the present work, we combined immunohistochemical and permeability studies to investigate the presence of tanycyte barriers along the ventricular walls of other brain CVOs. Our data indicate that, unlike cuboidal ependymal cells, ependymal cells bordering the CVOs possess long processes that project into the parenchyma of the CVOs to reach the fenestrated capillary network. Remarkably, these tanycyte-like cells display well-organized tight junctions around their cell bodies. Consistent with these observations, permeability studies show that this ependymal layer acts as a diffusion barrier. Together, our results suggest that tanycytes are a characteristic feature of all CVOs and yield potential new insights into their involvement in regulating the exchange between the blood, the brain, and the CSF within these “brain windows.” PMID:23649873

  18. Fluoroscopy-Guided Lumbar Drainage of Cerebrospinal Fluid for Patients in Whom a Blind Beside Approach Is Difficult

    PubMed Central

    Chee, Choong Guen; Lee, Joon Woo; Lee, Eugene; Kang, Heung Sik

    2015-01-01

    Objective To evaluate the rates of technical success, clinical success, and complications of fluoroscopy-guided lumbar cerebrospinal fluid drainage. Materials and Methods This retrospective study was approved by the Institutional Review Board of our hospital, and informed consent was waived. Ninety-six procedures on 60 consecutive patients performed July 2008 to December 2013 were evaluated. The patients were referred for the fluoroscopy-guided procedure due to failed attempts at a bedside approach, a history of lumbar surgery, difficulty cooperating, or obesity. Fluoroscopy-guided lumbar drainage procedures were performed in the lateral decubitus position with a midline puncture of L3/4 in the interspinous space. The catheter tip was positioned at the T12/L1 level, and the catheter was visualized on contrast agent-aided fluoroscopy. A standard angiography system with a rotatable C-arm was used. The definitions of technical success, clinical success, and complications were defined prior to the study. Results The technical and clinical success rates were 99.0% (95/96) and 89.6% (86/96), respectively. The mean hospital stay for an external lumbar drain was 4.84 days. Nine cases of minor complications and eight major complications were observed, including seven cases of meningitis, and one retained catheter requiring surgical removal. Conclusion Fluoroscopy-guided external lumbar drainage is a technically reliable procedure in difficult patients with failed attempts at a bedside procedure, history of lumbar surgery, difficulties in cooperation, or obesity. PMID:26175586

  19. Mir-203-mediated tricellulin mediates lead-induced in vitro loss of blood-cerebrospinal fluid barrier (BCB) function.

    PubMed

    Su, Peng; Zhao, Fang; Cao, Zipeng; Zhang, Jianbin; Aschner, Michael; Luo, Wenjing

    2015-08-01

    The blood-cerebrospinal fluid barrier (BCB) plays a critical role in the maintenance of optimal brain function. Tricellulin (TRIC), a protein localized at the tricellular contact sites of epithelial cells is involved in the formation of tight junctions in various epithelial barriers. However, little is known about its expression in the choroidal epithelial cells. It is well established that lead (Pb) exposure increases the leakage of the BCB. The purpose of this study is to investigate the expression and localization of TRIC in choroidal epithelial cells in vitro and whether altered TRIC expression mediates Pb-induced loss of barrier function. We found that TRIC protein and mRNA were expressed in choroidal epithelial cells in vitro and TRIC was localized at the tricellular contacts, colocalizing with occludin. Downregulation of TRIC by siRNA increased the BCB permeability corroborated by altered transendothelial electrical resistance (TEER) and FITC-dextran flux. Treatment with 10?M Pb reduced TRIC protein expression, but overexpression of TRIC alleviated the Pb-induced increase in BCB permeability. Bioinformatics analysis showed that mir-203 was a potential microRNA (miRNA) binding motif on TRIC 3'UTR, and that Pb exposure increased the expression of mir-203. Treatment with a mir-203 inhibitor increased TRIC protein expression and attenuated the Pb-induced BCB leakage. Our results establish that TRIC plays an important role in regulating BCB function. PMID:25975750

  20. Preanalytical Confounding Factors in the Analysis of Cerebrospinal Fluid Biomarkers for Alzheimer’s Disease: The Issue of Diurnal Variation

    PubMed Central

    Cicognola, Claudia; Chiasserini, Davide; Parnetti, Lucilla

    2015-01-01

    Given the growing use of cerebrospinal fluid (CSF) beta-amyloid (A?) and tau as biomarkers for early diagnosis of Alzheimer’s disease (AD), it is essential that the diagnostic procedures are standardized and the results comparable across different laboratories. Preanalytical factors are reported to be the cause of at least 50% of the total variability. Among them, diurnal variability is a key issue and may have an impact on the comparability of the values obtained. The available studies on this issue are not conclusive so far. Fluctuations of CSF biomarkers in young healthy volunteers have been previously reported, while subsequent studies have not confirmed those observations in older subjects, the ones most likely to receive this test. The observed differences in circadian rhythms need to be further assessed not only in classical CSF biomarkers but also in novel forthcoming biomarkers. In this review, the existing data on the issue of diurnal variations of CSF classical biomarkers for AD will be analyzed, also evaluating the available data on new possible biomarkers. PMID:26175714

  1. Marked Elevation of Excitatory Amino Acids in Cerebrospinal Fluid Obtained From Patients With Rotavirus-Associated Encephalopathy.

    PubMed

    Kashiwagi, Yasuyo; Kawashima, Hisashi; Suzuki, Shunsuke; Nishimata, Shigeo; Takekuma, Koji; Hoshika, Akinori

    2015-07-01

    Rotavirus is the most common cause of severe gastroenteritis in young children; however, its pathogenesis and immunity are not completely understood. Even less well recognized is rotavirus-induced central nervous system (CNS) involvement, which has been associated with seizure, encephalopathy and death, among others. To elucidate the host response to rotavirus infection, we retrospectively examined neurotransmitter amino acids in the cerebrospinal fluid (CSF) of 19 children with CNS involvement associated with rotavirus infection. Subjects were classified into two groups: those with encephalopathy followed by prolonged seizure (encephalopathy group) and those who had experienced afebrile, brief cluster of seizures without encephalopathy (cluster group). The levels of glutamate, glycine, and taurine in the encephalopathy group were significantly higher than those in the cluster group. Increased levels of excitatory amino acids in the CSF may induce neurological disorders and be related to disorder severity. To the best of our knowledge, this is the first report regarding amino acids in the CSF obtained from patients with rotavirus-induced CNS involvement. Further study is necessary to elucidate the role of CSF amino acid levels in rotavirus-induced CNS involvement. PMID:25130628

  2. An integrated workflow for multiplex CSF proteomics and peptidomics-identification of candidate cerebrospinal fluid biomarkers of Alzheimer's disease.

    PubMed

    Hölttä, Mikko; Minthon, Lennart; Hansson, Oskar; Holmén-Larsson, Jessica; Pike, Ian; Ward, Malcolm; Kuhn, Karsten; Rüetschi, Ulla; Zetterberg, Henrik; Blennow, Kaj; Gobom, Johan

    2015-02-01

    Many disease processes in the brain are reflected in the protein composition of the cerebrospinal fluid (CSF). In addition to proteins, CSF also contains a large number of endogenous peptides whose potential as disease biomarkers largely remains to be explored. We have developed a novel workflow in which multiplex isobaric labeling is used for simultaneous quantification of endogenous CSF peptides and proteins by liquid chromatography coupled with mass spectrometry. After the labeling of CSF samples, endogenous peptides are separated from proteins by ultrafiltration. The proteins retained on the filters are trypsinized, and the tryptic peptides are collected separately. We evaluated this technique in a comparative pilot study of CSF peptide and protein profiles in eight patients with Alzheimer's disease (AD) and eight nondemented controls. We identified several differences between the AD and control group among endogenous peptides derived from proteins known to be associated with AD, including neurosecretory protein VGF (ratios AD/controls 0.45-0.81), integral membrane protein 2B (ratios AD/controls 0.72-0.84), and metallothionein-3 (ratios AD/controls 0.51-0.61). Analysis of tryptic peptides identified several proteins that were altered in the AD group, some of which have previously been reported as changed in AD, for example, VGF (ratio AD/controls 0.70). PMID:25490617

  3. Lateral ventricular cerebrospinal fluid diffusivity as a potential neuroimaging marker of brain temperature in multiple sclerosis: a hypothesis and implications.

    PubMed

    Hasan, Khader M; Lincoln, John A; Nelson, Flavia M; Wolinsky, Jerry S; Narayana, Ponnada A

    2015-04-01

    In this retrospective study we tested the hypothesis that the net effect of impaired electrical conduction and therefore increased heat dissipation in multiple sclerosis (MS) results in elevated lateral ventricular (LV) cerebrospinal fluid (CSF) diffusivity as a measure of brain temperature estimated in vivo using diffusion tensor imaging (DTI). We used validated DTI-based segmentation methods to obtain normalized LV-CSF volume and its corresponding CSF diffusivity in 108 MS patients and 103 healthy controls in the age range of 21-63 years. The LV CSF diffusivity was ~2% higher in MS compared to controls that correspond to a temperature rise of ~1°C that could not be explained by changes in the CSF viscosity due to altered CSF protein content in MS. The LV diffusivity decreased with age in healthy controls (r=-0.29; p=0.003), but not in MS (r=0.15; p=0.11), possibly related to MS pathology. Age-adjusted LV diffusivity increased with lesion load (r=0.518; p=1×10(-8)). Our data suggest that the total brain lesion load is the primary contributor to the increase in LV CSF diffusivity in MS. These findings suggest that LV diffusivity is a potential in vivo biomarker of the mismatch between heat generation and dissipation in MS. We also discuss limitations and possible confounders. PMID:25485790

  4. Sustained increases in plasma C-type natriuretic peptides fail to increase concentrations in cerebrospinal fluid: Evidence from pregnant sheep.

    PubMed

    Wilson, Michele O; Barrell, Graham K; Prickett, Timothy C R; Espiner, Eric A

    2015-07-01

    C-type natriuretic peptide (CNP) is a paracrine growth factor with high abundance in CNS tissues and cerebrospinal fluid (CSF). Consistent with findings of CNP transcripts in the cerebral microvasculature and hypothalamus, CNP increases the permeability of the blood-brain barrier and reduces food intake when administered intracerebroventricularly in rodents. Whether high concentrations of CNP in plasma can affect CSF levels is unknown. Accordingly we have studied changes (days 4, 87 and 116) in concurrent plasma and CSF concentrations of CNP peptides in pregnant sheep - a physiologically unique setting in which plasma CNP is elevated for prolonged periods. Preliminary studies in non pregnant sheep showed stable CNP levels in CSF during repetitive sampling. Compared with values in non pregnant controls, plasma concentrations of CNP peptides were markedly raised (30-fold) at days 87 and 116 in pregnant sheep, yet CSF levels in the two groups did not differ. CNP peptides in CSF decreased from day 4 to day 87 in pregnant sheep, possibly reflecting an adaptive response of the cerebral vasculature to increased hemodynamic load. We conclude that sustained high concentrations of CNP - far exceeding levels encountered in human pathophysiology - fail to affect CNP peptide levels in CSF. PMID:25913855

  5. Cerebrospinal fluid-targeted delivery of neutralizing anti-IFN? antibody delays motor decline in an ALS mouse model.

    PubMed

    Otsmane, Belkacem; Aebischer, Julianne; Moumen, Anice; Raoul, Cédric

    2014-01-01

    Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the selective and gradual loss of motoneurons in the brain and spinal cord. A persistent inflammation, typified by the activation of astrocytes and microglia, accompanies the progressive degeneration of motoneurons. Interferon gamma (IFN?), a potent proinflammatory cytokine that is aberrantly present in the spinal cord of ALS mice and patients, has been proposed to contribute to motoneuron death by eliciting the activation of the lymphotoxin-? receptor (LT-?R) through its ligand LIGHT. However, the implication of IFN? in the pathogenic process remains elusive. Here, we show that an antagonistic anti-IFN? antibody efficiently rescues motoneurons from IFN?-induced death. When transiently delivered in the cerebrospinal fluid through a subcutaneously implanted osmotic minipump, the neutralizing anti-IFN? antibody significantly retarded motor function decline in a mouse model of ALS. However, this transient infusion of anti-IFN? antibody did not increase the life expectancy of ALS mice. Our results suggest that IFN? contributes to ALS pathogenesis and represents a potential therapeutic target for ALS. PMID:24145774

  6. Determination of bacterial meningitis: a retrospective study of 80 cerebrospinal fluid specimens evaluated by four in vitro methods.

    PubMed Central

    Wasilauskas, B L; Hampton, K D

    1982-01-01

    A total of 80 cerebrospinal fluid specimens were analyzed for bacterial meningitis by four procedures readily available to most laboratories. These tests included routine culturing. Gram staining, countercurrent immunoelectrophoresis, staphylococcal coagglutination (CoA) with laboratory-prepared reagents, and CoA with Pharmacia Diagnostics reagents. A total of 56 specimens were positive for bacterial agents by routine culturing: Gram stain results were positive for 64% of all specimens positive by culturing. For 36 specimens from patients with suspected meningitis due to either Haemophilus influenzae type b, Streptococcus pneumoniae, or group B streptococci, detection was 97% with Pharmacia CoA reagents, 94% with laboratory-prepared CoA reagents, 89% with routine culturing, 78% with countercurrent immunoelectrophoresis, and 75% with Gram staining. One specimen which contained Klebsiella pneumoniae was false positive for S. pneumoniae in tests with both of the CoA reagents and in countercurrent immunoelectrophoresis. A Gram stain of this specimen clearly showed gram-negative bacilli, which were confirmed by culturing. Although a positive culture and a positive Gram stain are definitive evidence of bacterial meningitis, rapid immunological tests can provide valuable clinical information as an adjunct to culture and Gram stain results. Serological tests with Pharmacia CoA reagents produced more positive results than either laboratory-prepared CoA reagents or countercurrent immunoelectrophoresis. PMID:6752193

  7. Is cerebrospinal fluid drainage of benefit to neuroprotection in patients undergoing surgery on the descending thoracic aorta or thoracoabdominal aorta?

    PubMed Central

    Bilal, Haris; O'Neill, Bridie; Mahmood, Sarah; Waterworth, Paul

    2012-01-01

    A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was ‘Is cerebrospinal fluid (CSF) drainage of benefit in patients undergoing surgery on the descending thoracic aorta or thoracoabdominal aorta?’ Altogether 1177 papers were found using the reported search, of which 17 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Ten of 13 studies demonstrate significant neurological protection from CSF drainage (±additional adjuncts), with two further papers showing no significant difference between patients who had or had not had CSF drainage and one study unable to provide any conclusions. For patients having surgery on the thoracic aorta or thoracoabdominal aorta CSF drainage, maintaining pressures <10 mmHg (P < 0.03), in conjunction with other neuroprotective strategies, minimizes the risk of neurological sequelae when compared with patients treated with similar adjuncts but without CSF drainage. The majority of studies used additional neuroprotective strategies, including cooling and reattachment of the intercostal arteries as adjuncts to CSF drainage. Logistic regression curves demonstrated that the longer the ischaemia time, the greater the benefit from CSF drainage (P < 0.04). Four papers observed complications of CSF drainage, of which the main complications were: catheter occlusion or dislodgement, headache, meningitis and subdural haematoma. Overall, CSF drainage does offer a neuroprotective benefit; preventing paraplegia if CSF pressures are maintained <10 mmHg. PMID:22761120

  8. Interaction between SCO-spondin and low density lipoproteins from embryonic cerebrospinal fluid modulates their roles in early neurogenesis

    PubMed Central

    Vera, América; Recabal, Antonia; Saldivia, Natalia; Stanic, Karen; Torrejón, Marcela; Montecinos, Hernán; Caprile, Teresa

    2015-01-01

    During early stages of development, encephalic vesicles are composed by a layer of neuroepithelial cells surrounding a central cavity filled with embryonic cerebrospinal fluid (eCSF). This fluid contains several morphogens that regulate proliferation and differentiation of neuroepithelial cells. One of these neurogenic factors is SCO-spondin, a giant protein secreted to the eCSF from early stages of development. Inhibition of this protein in vivo or in vitro drastically decreases the neurodifferentiation process. Other important neurogenic factors of the eCSF are low density lipoproteins (LDL), the depletion of which generates a 60% decrease in mesencephalic explant neurodifferentiation. The presence of several LDL receptor class A (LDLrA) domains (responsible for LDL binding in other proteins) in the SCO-spondin sequence suggests a possible interaction between both molecules. This possibility was analyzed using three different experimental approaches: (1) Bioinformatics analyses of the SCO-spondin region, that contains eight LDLrA domains in tandem, and of comparisons with the LDL receptor consensus sequence; (2) Analysis of the physical interactions of both molecules through immunohistochemical colocalization in embryonic chick brains and through the immunoprecipitation of LDL with anti-SCO-spondin antibodies; and (3) Analysis of functional interactions during the neurodifferentiation process when these molecules were added to a culture medium of mesencephalic explants. The results revealed that LDL and SCO-spondin interact to form a complex that diminishes the neurogenic capacities that both molecules have separately. Our work suggests that the eCSF is an active signaling center with a complex regulation system that allows for correct brain development.

  9. Cerebrospinal Fluid Enhancement on Fluid Attenuated Inversion Recovery Images After Carotid Artery Stenting with Neuroprotective Balloon Occlusions: Hemodynamic Instability and Blood-Brain Barrier Disruption

    SciTech Connect

    Ogami, Ryo, E-mail: ogami.r@mazda.co.jp; Nakahara, Toshinori [Mazda Hospital, Department of Neurosurgery (Japan); Hamasaki, Osamu [Shimane Prefectural Central Hospital, Department of Neurosurgery (Japan); Araki, Hayato [Mazda Hospital, Department of Neurosurgery (Japan); Kurisu, Kaoru [Hiroshima University Graduate School of Biomedical Sciences, Department of Neurosurgery (Japan)

    2011-10-15

    Purpose: A rare complication of carotid artery stenting (CAS), prolonged reversible neurological symptoms with delayed cerebrospinal fluid (CSF) space enhancement on fluid attenuated inversion recovery (FLAIR) images, is associated with blood-brain barrier (BBB) disruption. We prospectively identified patients who showed CSF space enhancement on FLAIR images. Methods: Nineteen patients-5 acute-phase and 14 scheduled-underwent 21 CAS procedures. Balloon catheters were navigated across stenoses, angioplasty was performed using a neuroprotective balloon, and stents were placed with after dilation under distal balloon protection. CSF space hyperintensity or obscuration on FLAIR after versus before CAS indicated CSF space enhancement. Correlations with clinical factors were examined. Results: CSF space was enhanced on FLAIR in 12 (57.1%) cases. Postprocedural CSF space enhancement was significantly related to age, stenosis rate, acute-stage procedure, and total occlusion time. All acute-stage CAS patients showed delayed enhancement. Only age was associated with delayed CSF space enhancement in scheduled CAS patients. Conclusions: Ischemic intolerance for severe carotid artery stenosis and temporary neuroprotective balloon occlusion, causing reperfusion injury, seem to be the main factors that underlie BBB disruption with delayed CSF space enhancement shortly after CAS, rather than sudden poststenting hemodynamic change. Our results suggest that factors related to hemodynamic instability or ischemic intolerance seem to be associated with post-CAS BBB vulnerability. Patients at risk for hemodynamic instability or with ischemic intolerance, which decrease BBB integrity, require careful management to prevent intracranial hemorrhagic and other post-CAS complications.

  10. Molecular biology of the blood-brain and the blood-cerebrospinal fluid barriers: similarities and differences.

    PubMed

    Redzic, Zoran

    2011-01-01

    Efficient processing of information by the central nervous system (CNS) represents an important evolutionary advantage. Thus, homeostatic mechanisms have developed that provide appropriate circumstances for neuronal signaling, including a highly controlled and stable microenvironment. To provide such a milieu for neurons, extracellular fluids of the CNS are separated from the changeable environment of blood at three major interfaces: at the brain capillaries by the blood-brain barrier (BBB), which is localized at the level of the endothelial cells and separates brain interstitial fluid (ISF) from blood; at the epithelial layer of four choroid plexuses, the blood-cerebrospinal fluid (CSF) barrier (BCSFB), which separates CSF from the CP ISF, and at the arachnoid barrier. The two barriers that represent the largest interface between blood and brain extracellular fluids, the BBB and the BCSFB, prevent the free paracellular diffusion of polar molecules by complex morphological features, including tight junctions (TJs) that interconnect the endothelial and epithelial cells, respectively. The first part of this review focuses on the molecular biology of TJs and adherens junctions in the brain capillary endothelial cells and in the CP epithelial cells. However, normal function of the CNS depends on a constant supply of essential molecules, like glucose and amino acids from the blood, exchange of electrolytes between brain extracellular fluids and blood, as well as on efficient removal of metabolic waste products and excess neurotransmitters from the brain ISF. Therefore, a number of specific transport proteins are expressed in brain capillary endothelial cells and CP epithelial cells that provide transport of nutrients and ions into the CNS and removal of waste products and ions from the CSF. The second part of this review concentrates on the molecular biology of various solute carrier (SLC) transport proteins at those two barriers and underlines differences in their expression between the two barriers. Also, many blood-borne molecules and xenobiotics can diffuse into brain ISF and then into neuronal membranes due to their physicochemical properties. Entry of these compounds could be detrimental for neural transmission and signalling. Thus, BBB and BCSFB express transport proteins that actively restrict entry of lipophilic and amphipathic substances from blood and/or remove those molecules from the brain extracellular fluids. The third part of this review concentrates on the molecular biology of ATP-binding cassette (ABC)-transporters and those SLC transporters that are involved in efflux transport of xenobiotics, their expression at the BBB and BCSFB and differences in expression in the two major blood-brain interfaces. In addition, transport and diffusion of ions by the BBB and CP epithelium are involved in the formation of fluid, the ISF and CSF, respectively, so the last part of this review discusses molecular biology of ion transporters/exchangers and ion channels in the brain endothelial and CP epithelial cells. PMID:21349151

  11. Molecular biology of the blood-brain and the blood-cerebrospinal fluid barriers: similarities and differences

    PubMed Central

    2011-01-01

    Efficient processing of information by the central nervous system (CNS) represents an important evolutionary advantage. Thus, homeostatic mechanisms have developed that provide appropriate circumstances for neuronal signaling, including a highly controlled and stable microenvironment. To provide such a milieu for neurons, extracellular fluids of the CNS are separated from the changeable environment of blood at three major interfaces: at the brain capillaries by the blood-brain barrier (BBB), which is localized at the level of the endothelial cells and separates brain interstitial fluid (ISF) from blood; at the epithelial layer of four choroid plexuses, the blood-cerebrospinal fluid (CSF) barrier (BCSFB), which separates CSF from the CP ISF, and at the arachnoid barrier. The two barriers that represent the largest interface between blood and brain extracellular fluids, the BBB and the BCSFB, prevent the free paracellular diffusion of polar molecules by complex morphological features, including tight junctions (TJs) that interconnect the endothelial and epithelial cells, respectively. The first part of this review focuses on the molecular biology of TJs and adherens junctions in the brain capillary endothelial cells and in the CP epithelial cells. However, normal function of the CNS depends on a constant supply of essential molecules, like glucose and amino acids from the blood, exchange of electrolytes between brain extracellular fluids and blood, as well as on efficient removal of metabolic waste products and excess neurotransmitters from the brain ISF. Therefore, a number of specific transport proteins are expressed in brain capillary endothelial cells and CP epithelial cells that provide transport of nutrients and ions into the CNS and removal of waste products and ions from the CSF. The second part of this review concentrates on the molecular biology of various solute carrier (SLC) transport proteins at those two barriers and underlines differences in their expression between the two barriers. Also, many blood-borne molecules and xenobiotics can diffuse into brain ISF and then into neuronal membranes due to their physicochemical properties. Entry of these compounds could be detrimental for neural transmission and signalling. Thus, BBB and BCSFB express transport proteins that actively restrict entry of lipophilic and amphipathic substances from blood and/or remove those molecules from the brain extracellular fluids. The third part of this review concentrates on the molecular biology of ATP-binding cassette (ABC)-transporters and those SLC transporters that are involved in efflux transport of xenobiotics, their expression at the BBB and BCSFB and differences in expression in the two major blood-brain interfaces. In addition, transport and diffusion of ions by the BBB and CP epithelium are involved in the formation of fluid, the ISF and CSF, respectively, so the last part of this review discusses molecular biology of ion transporters/exchangers and ion channels in the brain endothelial and CP epithelial cells. PMID:21349151

  12. Endoscopic endonasal repair of spontaneous sphenoid sinus lateral wall meningocele presenting with cerebrospinal fluid leak

    PubMed Central

    Y?ld?r?m, Ali Erdem; D?vanl?oglu, Denizhan; Cetinalp, Nuri Eralp; Belen, Ahmed Deniz

    2014-01-01

    Spontaneous sphenoid sinus lateral wall meningoceles are rare lesions with an unknown etiology. Endoscopic endonasal technique is a considerable route in the treatment of this condition. The aim of this paper is to report the etiology, surgical technique, and outcome in a patient repaired via endoscopic endonasal approach. A 51-year-old male patient applied with rhinorrhea started three months ago after an upper respiratory infection. There were no history of trauma or sinus operation. Biochemical analysis of the fluid was positive for beta-2-transferrin. This asypthomatic patient had undergone for repairment of lateral sphenoid sinus meningocele with endoscopic endonasal transsphenoidal approach. After endoscopic endonasal meningocele closure procedure no complications occured and a quick recovery was observed. Endoscopic endonasal approach is an effective and safe treatment modality of spontaneous lateral sphenoid sinus meningoceles and efficient in anterior skull base reconstruction. PMID:24966559

  13. [Cerebrospinal fluid viral load in HIV-1 positive hemophilic patients treated with HAART].

    PubMed

    Corti, M E; Villafañe, M F; Baré, P; Alves Rosa, F; Cermelj, M; Candela, M; Pérez Bianco, R; Tezanos Pinto, M

    2001-01-01

    As HIV seropositive patients with undetectable CSF viral load have a lower likelihood of developing neurologic disease, the determination of CSF viral load levels may be useful to evaluate the efficacy of HAART. We compared plasma viral load levels with HIV-1 RNA CSF levels in 18 hemophilic patients without neurocognitive involvement under HAART. We detected a significant correlation between plasma viral load levels and CSF viral load levels. Fourteen patients with undetectable plasma viral load had undetectable RNA HIV-1 CSF levels as well. Four patients with detectable plasma viral load had detectable HIV-RNA in CSF, but the latter were significantly lower. Viral load is usually lower in non-blood fluids and HAART decreases the viral load in CSF as well as in blood. PMID:11808421

  14. Diagnostic value of interleukin-10 in cerebrospinal fluid for diffuse large B-cell lymphoma of the central nervous system.

    PubMed

    Sasagawa, Yasuo; Akai, Takuya; Tachibana, Osamu; Iizuka, Hideaki

    2015-01-01

    A biomarker for early diagnosis of central nervous system (CNS) lymphoma would permit early treatment for attenuation of disease progression and neurological deterioration. High interleukin-10 (IL-10) or an IL-10/IL-6 ratio >1.0 are informative parameters for discriminating intraocular lymphomas from uveitis. Recent reports have also shown that CSF IL-10 is a potential diagnostic biomarker for CNS lymphoma. The purpose of this study was to evaluate the diagnostic value of IL-10 in cerebrospinal fluid (CSF) in patients with CNS lymphoma compared with other CNS diseases, including CNS tumors and inflammatory diseases. CSF IL-10, IL-6, beta-2 microglobulin, soluble IL-2 receptor and FDG-PET SUVmax were measured in 19 patients with CNS lymphoma (15 primary and 4 secondary diffuse large B-cell lymphomas) and 26 non-lymphoma patients with various brain tumors and inflammatory diseases. The diagnostic accuracy of the respective examinations for differentiation of CNS lymphomas from non-lymphomas was evaluated by receiver operating characteristic (ROC) curve analysis. The area under the ROC curve (AUC) was calculated. CSF IL-10 was detected at significant levels (median, 28 pg/ml; range <2-4,100 pg/ml) in all except one patient with CNS lymphoma, but not detected in any non-lymphoma patients. CSF IL-10 had the highest diagnostic accuracy with AUC = 0.974. At an IL-10 cutoff of 3 pg/ml, the sensitivity and specificity were 94.7 and 100 %, respectively. These results indicate that CSF IL-10 is a superior biomarker for initial screening for patients with CNS lymphoma. PMID:25258254

  15. Association between NME8 Locus Polymorphism and Cognitive Decline, Cerebrospinal Fluid and Neuroimaging Biomarkers in Alzheimer's Disease

    PubMed Central

    Liu, Ying; Yu, Jin-Tai; Wang, Hui-Fu; Hao, Xiao-Ke; Yang, Yu-Fen; Jiang, Teng; Zhu, Xi-Chen; Cao, Lei; Zhang, Dao-Qiang; Tan, Lan

    2014-01-01

    Recently, a large meta-analysis of five genome wide association studies (GWAS) identified a novel locus (rs2718058) adjacent to NME8 that played a preventive role in Alzheimer's disease (AD). However, this link between the single nucleotide polymorphism (SNP) rs2718058 and the pathology of AD have not been mentioned yet. Therefore, this study assessed the strength of association between the NME8 rs2718058 genotypes and AD-related measures including the cerebrospinal fluid (CSF) amyloid beta, tau, P-tau concentrations, neuroimaging biomarkers and cognitive performance, in a large cohort from Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We used information of a total of 719 individuals, including 211 normal cognition (NC), 346 mild cognitive impairment (MCI) and 162 AD. Although we didn't observe a positive relationship between rs2718058 and AD, it was significantly associated with several AD related endophenotypes. Among the normal cognitively normal participants, the minor allele G carriers showed significantly associated with higher CDRSB score than A allele carriers (P?=?0.021). Occipital gyrus atrophy were significantly associated with NME8 genotype status (P?=?0.002), with A allele carriers has more atrophy than the minor allele G carriers in AD patients; lateral ventricle (both right and left) cerebral metabolic rate for glucose (CMRgl) were significantly associated with NME8 genotype (P<0.05), with GA genotype had higher metabolism than GG and AA genotypes in MCI group; the atrophic right hippocampus in 18 months is significantly different between the three group, with GG and AA genotypes had more hippocampus atrophy than GA genotypes in the whole group. Together, our results are consistent with the direction of previous research, suggesting that NME8 rs2718058 appears to play a role in lowering the brain neurodegeneration. PMID:25486118

  16. Transmigration of polymorphnuclear neutrophils and monocytes through the human blood-cerebrospinal fluid barrier after bacterial infection in vitro

    PubMed Central

    2013-01-01

    Background Bacterial invasion through the blood-cerebrospinal fluid barrier (BCSFB) during bacterial meningitis causes secretion of proinflammatory cytokines/chemokines followed by the recruitment of leukocytes into the CNS. In this study, we analyzed the cellular and molecular mechanisms of polymorphonuclear neutrophil (PMN) and monocyte transepithelial transmigration (TM) across the BCSFB after bacterial infection. Methods Using an inverted transwell filter system of human choroid plexus papilloma cells (HIBCPP), we studied leukocyte TM rates, the migration route by immunofluorescence, transmission electron microscopy and focused ion beam/scanning electron microscopy, the secretion of cytokines/chemokines by cytokine bead array and posttranslational modification of the signal regulatory protein (SIRP) ? via western blot. Results PMNs showed a significantly increased TM across HIBCPP after infection with wild-type Neisseria meningitidis (MC58). In contrast, a significantly decreased monocyte transmigration rate after bacterial infection of HIBCPP could be observed. Interestingly, in co-culture experiments with PMNs and monocytes, TM of monocytes was significantly enhanced. Analysis of paracellular permeability and transepithelial electrical resistance confirmed an intact barrier function during leukocyte TM. With the help of the different imaging techniques we could provide evidence for para- as well as for transcellular migrating leukocytes. Further analysis of secreted cytokines/chemokines showed a distinct pattern after stimulation and transmigration of PMNs and monocytes. Moreover, the transmembrane glycoprotein SIRP? was deglycosylated in monocytes, but not in PMNs, after bacterial infection. Conclusions Our findings demonstrate that PMNs and monoctyes differentially migrate in a human BCSFB model after bacterial infection. Cytokines and chemokines as well as transmembrane proteins such as SIRP? may be involved in this process. PMID:23448224

  17. Cerebrospinal fluid of newly diagnosed amyotrophic lateral sclerosis patients exhibits abnormal levels of selenium species including elevated selenite

    PubMed Central

    Vinceti, Marco; Solovyev, Nikolay; Mandrioli, Jessica; Crespi, Catherine M.; Bonvicini, Francesca; Arcolin, Elisa; Georgoulopoulou, Eleni; Michalke, Bernhard

    2013-01-01

    Exposure to selenium, and particularly to its inorganic forms, has been hypothesized as a risk factor for amyotrophic lateral sclerosis (ALS), a fast progressing motor neuron disease with poorly understood etiology. However, no information is known about levels of inorganic and some organic selenium species in the central nervous system of ALS patients, and recent observations suggest that peripheral biomarkers of exposure are unable to predict these levels for several Se species including the inorganic forms. Using a hospital-referred cases-control series and advanced selenium speciation methods, we compared the chemical species of selenium in cerebrospinal fluid from thirty-eight ALS patients to those of thirty-eight reference neurological patients matched on age and gender. We found that higher concentrations of inorganic selenium in the form of selenite and of human serum albumin-bound selenium were associated with increased ALS risk (relative risks 3.9 (95% confidence interval 1.2–11.0) and 1.7 (1.0–2.9) for 0.1µg/l increase). Conversely, lower concentrations of selenoprotein P-bound selenium were associated with increased risk (relative risk 0.2 for 1µg/l increase, 95% confidence interval 0.04–0.8). The associations were stronger among cases age 50 years or older, who are postulated to have lower rates of genetic disease origin. These results suggest that excess selenite and human serum albumin bound-selenium and low levels of selenoprotein P-bound selenium in the central nervous system, which may be related, may play a role in ALS etiology. PMID:23732511

  18. Cerebrospinal Fluid ?-Synuclein and Lewy Body-Like Symptoms in Normal Controls, Mild Cognitive Impairment, and Alzheimer’s Disease

    PubMed Central

    Mackin, R. Scott; Insel, Philip; Zhang, Jing; Mohlenhoff, Brian; Galasko, Douglas; Weiner, Michael; Mattsson, Niklas

    2015-01-01

    Background Reduced cerebrospinal fluid (CSF) ?-synuclein has been described in synucleinopathies, including dementia with Lewy bodies (DLB). Common symptoms of DLB include visual hallucinations and visuospatial and executive deficits. Co-occurrence of Lewy body pathology is common in Alzheimer’s disease (AD) patients, but it is unknown if reduced CSF ?-synuclein is associated with Lewy body-like symptomatology in AD. Objective Determine associations between CSF ?-synuclein and Lewy body-like symptomatology. Methods We included 73 controls (NC), 121 mild cognitive impairment (MCI) patients, and 61 AD patients (median follow-up 3.5 years, range 0.6–7.8). We tested associations between baseline CSF ?-synuclein and visual hallucinations and (longitudinal) cognition. Models were tested with and without co-varying for CSF total tau (T-tau), which is elevated in AD patients, and believed to reflect neurodegeneration. Results Hallucinations were reported in 20% of AD patients, 13% of MCI patients, and 8% of NC. In AD, low CSF ?-synuclein was associated with hallucinations. When adjusting for CSF T-tau, low CSF ?-synuclein was associated with accelerated decline of executive function (NC, MCI, and AD), memory (MCI and AD), and language (MCI). Conclusion The associations of low CSF ?-synuclein with hallucinations and poor executive function, which are hallmarks of DLB, indirectly suggest that this biomarker may reflect underlying synuclein pathology. The associations with memory and language in MCI and AD suggests either that reduced CSF ?-synuclein also partly reflects global impaired neuronal/synaptic function, or that non-specific overall cognitive deterioration is accelerated in the presence of synuclein related pathology. The findings will require autopsy verification. PMID:25125463

  19. Quantitative analysis of human cerebrospinal fluid proteins using a combination of cysteine tagging and amine-reactive isobaric labeling.

    PubMed

    Giron, Priscille; Dayon, Loïc; Turck, Natacha; Hoogland, Christine; Sanchez, Jean-Charles

    2011-01-01

    Highly complex and dynamic protein mixtures are hardly comprehensively resolved by direct shotgun proteomic analysis. As many proteins of biological interest are of low abundance, numerous analytical methodologies have been developed to reduce sample complexity and go deeper into proteomes. The present work describes an analytical strategy to perform cysteinyl-peptide subset enrichment and relative quantification through successive cysteine and amine-isobaric tagging. A cysteine-reactive covalent capture tag (C³T) allowed derivatization of cysteines and specific isolation on a covalent capture (CC) resin. The 6-plex amine-reactive tandem mass tags (TMT) served for relative quantification of the targeted peptides. The strategy was first evaluated on a model protein mixture with increasing concentrations to assess the specificity of the enrichment and the quantitative performances of the workflow. It was then applied to human cerebrospinal fluid (CSF) from post-mortem and ante-mortem samples. These studies confirmed the specificity of the C³T and the CC technique to cysteine-containing peptides. The model protein mixture analysis showed high precision and accuracy of the quantification with coefficients of variation and mean absolute errors of less than 10% on average. The CSF experiments demonstrated the potential of the strategy to study complex biological samples and identify differential brain-related proteins. In addition, the quantification data were highly correlated with a classical TMT experiment (i.e., without C³T cysteine-tagging and enrichment steps). Altogether, these results legitimate the use of this quantitative C³T strategy to enrich and relatively quantify cysteine-containing peptides in complex mixtures. PMID:20973565

  20. Association between NME8 locus polymorphism and cognitive decline, cerebrospinal fluid and neuroimaging biomarkers in Alzheimer's disease.

    PubMed

    Liu, Ying; Yu, Jin-Tai; Wang, Hui-Fu; Hao, Xiao-Ke; Yang, Yu-Fen; Jiang, Teng; Zhu, Xi-Chen; Cao, Lei; Zhang, Dao-Qiang; Tan, Lan

    2014-01-01

    Recently, a large meta-analysis of five genome wide association studies (GWAS) identified a novel locus (rs2718058) adjacent to NME8 that played a preventive role in Alzheimer's disease (AD). However, this link between the single nucleotide polymorphism (SNP) rs2718058 and the pathology of AD have not been mentioned yet. Therefore, this study assessed the strength of association between the NME8 rs2718058 genotypes and AD-related measures including the cerebrospinal fluid (CSF) amyloid beta, tau, P-tau concentrations, neuroimaging biomarkers and cognitive performance, in a large cohort from Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We used information of a total of 719 individuals, including 211 normal cognition (NC), 346 mild cognitive impairment (MCI) and 162 AD. Although we didn't observe a positive relationship between rs2718058 and AD, it was significantly associated with several AD related endophenotypes. Among the normal cognitively normal participants, the minor allele G carriers showed significantly associated with higher CDRSB score than A allele carriers (P = 0.021). Occipital gyrus atrophy were significantly associated with NME8 genotype status (P = 0.002), with A allele carriers has more atrophy than the minor allele G carriers in AD patients; lateral ventricle (both right and left) cerebral metabolic rate for glucose (CMRgl) were significantly associated with NME8 genotype (P < 0.05), with GA genotype had higher metabolism than GG and AA genotypes in MCI group; the atrophic right hippocampus in 18 months is significantly different between the three group, with GG and AA genotypes had more hippocampus atrophy than GA genotypes in the whole group. Together, our results are consistent with the direction of previous research, suggesting that NME8 rs2718058 appears to play a role in lowering the brain neurodegeneration. PMID:25486118

  1. Increased levels of interleukins 2 and 17 in the cerebrospinal fluid of patients with idiopathic intracranial hypertension

    PubMed Central

    Edwards, Laura J; Sharrack, Basil; Ismail, Azza; Tench, Christopher R; Gran, Bruno; Dhungana, Samish; Brettschneider, Johannes; Tumani, Hayrettin; Constantinescu, Cris S

    2013-01-01

    IIH is a condition of raised intracranial pressure of unknown pathogenesis, which is most commonly seen in young overweight women. This study was designed to confirm and extend previous reports by our and other groups showing increased inflammatory cytokine expression in patients with IIH. We analyzed the concentrations of 14 cytokines (IL-1?, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17, IL-22, IL-23, IFN?, TNF?, TGF?, and osteopontin) in the serum and cerebrospinal fluid (CSF) of 17 patients with IIH and 53 patients with other neurological conditions. Patients with IIH had highly elevated IL-2, IL-4, IL-10, IL-17 and IFN? in the CSF compared to patients with multiple sclerosis or non-organic/non-inflammatory neurological conditions. No significant differences were seen between serum cytokine levels in four patient groups (IIH - multiple sclerosis - inflammatory neurological conditions - non-organic/non-inflammatory neurological conditions) and there were no correlations between serum and CSF cytokine levels. In IIH, levels of IL-2, IL-8 and IL-17 were significantly higher in CSF than serum; levels of IL-1?, IL-4, IL-22, IFN? and TNF? were significantly higher in serum than CSF. For most cytokines, the CSF/serum cytokine ratio was significantly higher than the CSF/serum albumin ratio, indicating intrathecal synthesis of these cytokines in IIH. We conclude that IIH is associated with elevated levels of IL-17 and IL-2 in the CSF, suggesting the involvement of these cytokines in disease pathogenesis. PMID:24179731

  2. Elevated Cellular Retinoic Acid Binding Protein-I in Cerebrospinal Fluid of Patients with Hemorrhagic Cerebrovascular Diseases : Preliminary Study

    PubMed Central

    Jeon, Jin Pyeong; Cho, Won-Sang; Kang, Hyun-Seung; Kim, Seung-Ki; Oh, Chang Wan

    2015-01-01

    Objective Elevated cellular retinoic acid binding protein-I (CRABP-I) is thought to be related to the abnormal proliferation and migration of smooth muscle cells (SMCs). Accordingly, a higher CRABP-I level could cause disorganized vessel walls by causing immature SMC phenotypes and altering extracellular matrix proteins which could result in vulnerable arterial walls with inadequate responses to hemodynamic stress. We hypothesized that elevated CRABP-I level in the cerebrospinal fluid (CSF) could be related to subarachnoid hemorrhage (SAH). Moreover, we also extended this hypothesis in patients with vascular malformation according to the presence of hemorrhage. Methods We investigated the CSF of 26 patients : SAH, n=7; unruptured intracranial aneurysm (UIA), n=7; arteriovenous malformation (AVM), n=4; cavernous malformation (CM), n=3; control group, n=5. The optical density of CRABP-I was confirmed by Western blotting and presented as mean±standard error of the measurement. Results CRABP-I in SAH (0.33±0.09) was significantly higher than that in the UIA (0.12±0.01, p=0.033) or control group (0.10±0.01, p=0.012). Hemorrhage presenting AVM (mean 0.45, ranged 0.30-0.59) had a higher CRABP-I level than that in AVM without hemorrhage presentation (mean 0.16, ranged 0.14-0.17). The CRABP-I intensity in CM with hemorrhage was 0.21 and 0.31, and for CM without hemorrhage 0.14. Overall, the hemorrhage presenting group (n=11, 0.34±0.06) showed a significantly higher CRABP-I intensity than that of the non-hemorrhage presenting group (n=10, 0.13±0.01, p=0.001). Conclusion The results suggest that elevated CRABP-I in the CSF could be related with aneurysm rupture. Additionally, a higher CRABP-I level seems to be associated with hemorrhage development in vascular malformation. PMID:25733988

  3. Immunophenotypic analysis of cerebrospinal fluid cell populations with the Cell-Dyn Sapphire haematology analyser: method feasibility and preliminary observations.

    PubMed

    Adam, P; Sobek, O; Scott, C S; Dolezil, D; Kasik, J; Hajdukova, L; Adam, D

    2010-02-01

    Cerebrospinal fluid (CSF) samples (n=50) from patients with neurological disease (bacterial infection, viral infection, neuroborreliosis and multiple sclerosis) were analysed to characterize cell populations by fluorescent immunocytometry with the CD-Sapphire haematology analyser. Reagent combinations applied to all CSF samples comprised CD3/CD19/HLA-DR and CD4/CD8, with some being further analysed using CD3/CD4, CD3/CD16 and CD3/CD25 protocols. Of the 50 samples, 11 were excluded because of high proportions of nonviable cells (n=2) or insufficient cell numbers (n=9). Apart from bacterial infection with granulocytosis, all diagnostic groups showed high proportions (51.4-77.0%) of CD3+ T cells. There was a modest association between T-cell and B-cell counts, but absolute B-cell numbers exceeded 5 cells/microl in only 7/39 cases (neuroborreliosis, n=6; bacterial meningitis, n=1). CD3/Ia antigen (activation) co-expression was low and only exceeded 5% in 7/39 samples with no diagnostic correlation. Primary CD4+ and CD8+ T-cell subsets showed similar quantitative trends and CD4/CD8 co-analysis revealed the presence in all diagnostic groups (neuroborreliosis and multiple sclerosis in particular) of a CD4+CD8int fraction that was predominantly CD3+ and CD16- and had a morphological profile consistent with small lymphoid cells. Supplementary CD-Sapphire cellular immunological analysis of most CSF samples is feasible using the procedure detailed in this communication. PMID:19500178

  4. Relative quantification of proteins in human cerebrospinal fluids by MS/MS using 6-plex isobaric tags.

    PubMed

    Dayon, Loïc; Hainard, Alexandre; Licker, Virginie; Turck, Natacha; Kuhn, Karsten; Hochstrasser, Denis F; Burkhard, Pierre R; Sanchez, Jean-Charles

    2008-04-15

    A new 6-plex isobaric mass tagging technology is presented, and proof of principle studies are carried out using standard protein mixtures and human cerebrospinal fluid (CSF) samples. The Tandem Mass Tags (TMT) comprise a set of structurally identical tags which label peptides on free amino-terminus and epsilon-amino functions of lysine residues. During MS/MS fragmentation, quantification information is obtained through the losses of the reporter ions. After evaluation of the relative quantification with the 6-plex version of the TMT on a model protein mixture at various concentrations, the quantification of proteins in CSF samples was performed using shotgun methods. Human postmortem (PM) CSF was taken as a model of massive brain injury and comparison was carried out with antemortem (AM) CSF. After immunoaffinity depletion, triplicates of AM and PM CSF pooled samples were reduced, alkylated, digested by trypsin, and labeled, respectively, with the six isobaric variants of the TMT (with reporter ions from m/z = 126.1 to 131.1 Th). The samples were pooled and fractionated by SCX chromatography. After RP-LC separation, peptides were identified and quantified by MS/MS analysis with MALDI TOF/TOF and ESI-Q-TOF. The concentration of 78 identified proteins was shown to be clearly increased in PM CSF samples compared to AM. Some of these proteins, like GFAP, protein S100B, and PARK7, have been previously described as brain damage biomarkers, supporting the PM CSF as a valid model of brain insult. ELISA for these proteins confirmed their elevated concentration in PM CSF. This work demonstrates the validity and robustness of the tandem mass tag (TMT) approach for quantitative MS-based proteomics. PMID:18312001

  5. (1,3)-?-d-glucan in cerebrospinal fluid for diagnosis of fungal meningitis associated with contaminated methylprednisolone injections.

    PubMed

    Malani, Anurag N; Singal, Bonita; Wheat, L Joseph; Al Sous, Ola; Summons, Theresa A; Durkin, Michelle M; Pettit, April C

    2015-03-01

    Prompt diagnosis and treatment of fungal meningitis are critical, but culture is insensitive. (1,3)-?-d-Glucan (BDG) testing is FDA approved for serological diagnosis of invasive fungal disease; however, BDG testing is not approved for cerebrospinal fluid (CSF), and the appropriate cutoff value is unknown. We aimed to validate the diagnostic accuracy of CSF BDG measurements for fungal meningitis among patients exposed to contaminated methylprednisolone acetate (MPA). A retrospective observational study was conducted at St. Joseph Mercy Hospital and Vanderbilt University from November 2013 to February 2014. Patients were included if they had received a contaminated MPA injection. Cases were classified as probable or proven meningitis according to Centers for Disease Control and Prevention guidelines. CSF BDG testing was performed according to the package insert instructions for serum samples, and results were validated using Clinical and Laboratory Standards Institute procedures (MiraVista Diagnostics). Of 233 patients, 45 had meningitis (28 proven cases), 53 had spinal/paraspinal infections (19 proven cases), and 135 did not develop disease. Using the manufacturer's cutoff value (?80 pg/ml), the sensitivity and specificity were 96% and 95%, respectively, for proven meningitis and 84% and 95% for probable or proven meningitis. Receiver operating characteristic analysis identified the optimal cutoff value for proven meningitis to be 66 pg/ml (sensitivity, 100%; specificity, 94%) and that for probable or proven meningitis to be 66 pg/ml (sensitivity, 91%; specificity, 92%). Our results suggest that CSF BDG measurements are highly sensitive and specific for the diagnosis of fungal meningitis associated with contaminated MPA injections. Further study on the utility of CSF BDG testing for other types of fungal meningitis is needed. PMID:25540391

  6. Risk factors for first cerebrospinal fluid shunt infection: findings from a multi-center prospective cohort study

    PubMed Central

    Simon, Tamara D.; Butler, Jerry; Whitlock, Kathryn B.; Browd, Samuel R.; Holubkov, Richard; Kestle, John R.W.; Kulkarni, Abhaya V.; Langley, Marcie; Limbrick, David D.; Mayer-Hamblett, Nicole; Tamber, Mandeep; Wellons, John C.; Whitehead, William E.; Riva-Cambrin, Jay

    2014-01-01

    Objective To quantify the extent to which revision(s) of cerebrospinal fluid (CSF) shunt are associated with increased risk of CSF shunt infection, after adjusting for patient factors that may contribute to infection risk. Study design We used the HCRN registry to assemble a large prospective six center cohort of 1,036 children undergoing initial CSF shunt placement between April 2008 and January 2012. The primary outcome of interest was first CSF shunt infection. Data for initial CSF shunt placement and all subsequent CSF shunt revisions prior to first CSF shunt infection, where applicable, were obtained. The risk of first infection was estimated using a multivariable Cox proportional hazard model accounting for patient characteristics and CSF shunt revisions, and is reported using hazard ratios (HR) with 95% confidence intervals (CI). Results Of the 102 children who developed first infection within 12 months of placement, 33 (32%) followed one or more CSF shunt revisions. Baseline factors independently associated with risk of first infection included: gastrostomy tube (HR 2.0, 95% CI: 1.1, 3.3), age 6–12 months (HR 0.3, 95% CI: 0.1, 0.8), and prior neurosurgery (HR 0.4, 95% CI: 0.2, 0.9). After controlling for baseline factors, infection risk was most significantly associated with the need for revision (1 revision vs. none, HR 3.9, 95% CI: 2.2, 6.5; ?2 revisions, HR 13.0, 95% CI: 6.5, 24.9). Conclusions This study quantifies the elevated risk of infection associated with shunt revisions observed in clinical practice. To reduce risk of infection risk further work should optimize revision procedures. PMID:24661340

  7. Cerebrospinal Fluid Levels of Amyloid Precursor Protein Are Associated with Ventricular Size in Post-Hemorrhagic Hydrocephalus of Prematurity

    PubMed Central

    Morales, Diego M.; Holubkov, Richard; Inder, Terri E.; Ahn, Haejun C.; Mercer, Deanna; Rao, Rakesh; McAllister, James P.; Holtzman, David M.; Limbrick, David D.

    2015-01-01

    Background Neurological outcomes of preterm infants with post-hemorrhagic hydrocephalus (PHH) remain among the worst in infancy, yet there remain few instruments to inform the treatment of PHH. We previously observed PHH-associated elevations in cerebrospinal fluid (CSF) amyloid precursor protein (APP), neural cell adhesion molecule-L1 (L1CAM), neural cell adhesion molecule-1 (NCAM-1), and other protein mediators of neurodevelopment. Objective The objective of this study was to examine the association of CSF APP, L1CAM, and NCAM-1 with ventricular size as an early step toward developing CSF markers of PHH. Methods CSF levels of APP, L1CAM, NCAM-1, and total protein (TP) were measured in 12 preterm infants undergoing PHH treatment. Ventricular size was determined using cranial ultrasounds. The relationships between CSF APP, L1CAM, and NCAM-1, occipitofrontal circumference (OFC), volume of CSF removed, and ventricular size were examined using correlation and regression analyses. Results CSF levels of APP, L1CAM, and NCAM-1 but not TP paralleled treatment-related changes in ventricular size. CSF APP demonstrated the strongest association with ventricular size, estimated by frontal-occipital horn ratio (FOR) (Pearson R = 0.76, p = 0.004), followed by NCAM-1 (R = 0.66, p = 0.02) and L1CAM (R = 0.57,p = 0.055). TP was not correlated with FOR (R = 0.02, p = 0.95). Conclusions Herein, we report the novel observation that CSF APP shows a robust association with ventricular size in preterm infants treated for PHH. The results from this study suggest that CSF APP and related proteins at once hold promise as biomarkers of PHH and provide insight into the neurological consequences of PHH in the preterm infant. PMID:25738507

  8. Transportin 1 in the mouse brain: appearance in regions of neurogenesis, cerebrospinal fluid production/sensing, and circadian clock.

    PubMed

    Sato, Miho; Mizoro, Yasutaka; Atobe, Yuta; Fujimoto, Yoshito; Yamaguchi, Yoshiaki; Fustin, Jean-Michel; Doi, Masao; Okamura, Hitoshi

    2011-06-15

    Transportin1 (Tnpo1) is a carrier protein belonging to the importin-? family, which transports substrates between the cytoplasm and the nucleus. To gain insight into the role of Tnpo1 gene in the brain, we investigated the localization of Tnpo1-, Tnpo2-, and Tnpo3-expressing cells by in situ hybridization histochemistry. Tnpo1 mRNA-positive cells were distributed throughout the brain from the olfactory bulb to the medulla oblongata. The cells in the subventricular zone of the lateral ventricle, where neurogenesis occurs even in the adult, and its progeny neurons in the granular cells of the olfactory bulb and the islands of Calleja were strongly labeled. It is also noteworthy that cerebrospinal fluid (CSF)-generating epithelial cells in the choroid plexus and CSF-contacting and -sensing circumventricular organs, including organum vasculosum lamina terminalis, subfornical organ, and subcommissural organ, expressed high amounts of Tnpo1. The strongest signals were found in the suprachiasmatic nucleus (SCN), where the biological clock resides, which prompted us to examine the circadian characteristics of Tnpo1. Under constant-dark conditions, the circadian expression profiles of Tnpo1 mRNA in the SCN showed a peak in the subjective night and a trough in the subjective day. Tnpo2 and Tnpo3 showed similar patterns of expression, except in the choroids plexus, the subventricular zone, and the SCN, where the expression was notably weaker. These findings suggest that Tnpo1 is involved in a variety of functions in the adult brain, including neurogenesis, CSF production and sensing, and circadian rhythms. PMID:21452213

  9. Multicenter Testing of the Rapid Quantification of Radical Oxygen Species in Cerebrospinal Fluid to Diagnose Bacterial Meningitis

    PubMed Central

    Lukaszewicz, Anne-Claire; Faivre, Valérie; Bout, Hélène; Gayat, Etienne; Lagergren, Tina; Damoisel, Charles; Bresson, Damien; Paugam, Catherine; Mantz, Jean; Payen, Didier

    2015-01-01

    Purpose Meningitis is a serious concern after traumatic brain injury (TBI) or neurosurgery. This study tested the level of reactive oxygen species (ROS) in cerebrospinal fluid (CSF) to diagnose meningitis in febrile patients several days after trauma or surgery. Methods Febrile patients (temperature > 38°C) after TBI or neurosurgery were included prospectively. ROS were measured in CSF within 4 hours after sampling using luminescence in the basal state and after cell stimulation with phorbol 12-myristate 13-acetate (PMA). The study was conducted in a single-center cohort 1 (n = 54, training cohort) and then in a multicenter cohort 2 (n = 136, testing cohort) in the Intensive Care and Neurosurgery departments of two teaching hospitals. The performance of the ROS test was compared with classical CSF criteria, and a diagnostic decision for meningitis was made by two blinded experts. Results The production of ROS was higher in the CSF of meningitis patients than in non-infected CSF, both in the basal state and after PMA stimulation. In cohort 1, ROS production was associated with a diagnosis of meningitis with an AUC of 0.814 (95% confidence interval (CI) [0.684–0.820]) for steady-state and 0.818 (95% CI [0.655–0.821]) for PMA-activated conditions. The best threshold value obtained in cohort 1 was tested in cohort 2 and showed high negative predictive values and low negative likelihood ratios of 0.94 and 0.36 in the basal state, respectively, and 0.96 and 0.24 after PMA stimulation, respectively. Conclusion The ROS test in CSF appeared suitable for eliminating a diagnosis of bacterial meningitis. PMID:26011286

  10. Quantitative detection of multiple gene promoter hypermethylation in tumor tissue, serum, and cerebrospinal fluid predicts prognosis of malignant gliomas

    PubMed Central

    Liu, Bo-Lin; Cheng, Jin-Xiang; Zhang, Wei; Zhang, Xiang; Wang, Rui; Lin, Hong; Huo, Jun-Li; Cheng, Hong

    2010-01-01

    Aberrant promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the malignant transformation in gliomas. We hypothesized that quantitative analysis of methylated genes will provide prognostic values in malignant glioma patients. We used an immunocapturing approach followed by real-time polymerase chain reaction analysis to detect altered patterns of promoter methylation in O-6-methylguanine-DNA methyltransferase (MGMT), p16INK4a, tissue inhibitor of metalloproteinase-3 (TIMP-3), and thrombospondin 1 (THBS1). The tumor tissue and paired serum as well as cerebrospinal fluid (CSF) from 66 patients with malignant gliomas were studied. Serum and CSF from 20 age-matched noncancer individuals were used as control. Promoter hypermethylation in MGMT, p16INK4a, TIMP-3, and THBS1 was detected at high frequencies in tumor tissue, serum, and CSF. None of the control serum or CSF showed aberrant methylation. Hypermethylation in serum and CSF DNA was all accompanied with methylation in the corresponding tumor tissues with 100% specificity. Highly elevated MGMT, p16INK4a, and THBS1 methylation levels in gliomas serum were the sole independent factors predicting inferior overall survival in this cohort. For progression-free survival, hypermethylation of MGMT and THBS1 in CSF were the independent prognostic factors. Multiple gene promoter hypermethylation analysis appears to be promising as a prognostic factor in glioma and as a mini-invasive tumor marker in serum and/or CSF DNA. Evaluation of these changes may help in selecting glioma patients for optimal adjuvant treatments and modifying chemotherapy. PMID:20154338

  11. Distinct cerebrospinal fluid amyloid ? peptide signatures in sporadic and PSEN1 A431E-associated familial Alzheimer's disease

    PubMed Central

    2010-01-01

    Background Alzheimer's disease (AD) is associated with deposition of amyloid ? (A?) in the brain, which is reflected by low concentration of the A?1-42 peptide in the cerebrospinal fluid (CSF). There are at least 15 additional A? peptides in human CSF and their relative abundance pattern is thought to reflect the production and degradation of A?. Here, we test the hypothesis that AD is characterized by a specific CSF A? isoform pattern that is distinct when comparing sporadic AD (SAD) and familial AD (FAD) due to different mechanisms underlying brain amyloid pathology in the two disease groups. Results We measured A? isoform concentrations in CSF from 18 patients with SAD, 7 carriers of the FAD-associated presenilin 1 (PSEN1) A431E mutation, 17 healthy controls and 6 patients with depression using immunoprecipitation-mass spectrometry. Low CSF levels of A?1-42 and high levels of A?1-16 distinguished SAD patients and FAD mutation carriers from healthy controls and depressed patients. SAD and FAD were characterized by similar changes in A?1-42 and A?1-16, but FAD mutation carriers exhibited very low levels of A?1-37, A?1-38 and A?1-39. Conclusion SAD patients and PSEN1 A431E mutation carriers are characterized by aberrant CSF A? isoform patterns that hold clinically relevant diagnostic information. PSEN1 A431E mutation carriers exhibit low levels of A?1-37, A?1-38 and A?1-39; fragments that are normally produced by ?-secretase, suggesting that the PSEN1 A431E mutation modulates ?-secretase cleavage site preference in a disease-promoting manner. PMID:20145736

  12. Reissner's fibre proteins and p73 variations in the cerebrospinal fluid and subcommissural organ of hydrocephalic rat.

    PubMed

    Carmona-Calero, E M; González-Marrero, I; González-Toledo, J M; Castañeyra-Ruiz, A; De Paz-Carmona, H; Castañeyra-Ruiz, L; Fernández-Rodriguez, P; Ruiz-Mayor, M L; Castañeyra-Perdomo, A

    2009-08-01

    Reissner's fibre (RF) is formed by the polymerization of the glycoprotein secreted by the subcommissural organ (SCO). The SCO also secretes soluble glycoprotein into the cerebrospinal fluid (CSF); variations in RF and SCO have been reported in hydrocephalus. On the other hand, hydrocephalus and other brain alterations have been described in p73 mutant mice. The p73 belongs to the tumour suppressor p53 protein family and has two isoforms: the TAp73 with apoptotic activity and DeltaNp73 with anti-apoptotic function. Moreover, the TAp73 isoform is glycosylated and secreted into the CSF. In the present work, we analysed the variations in RF and p73 proteins in the CSF and SCO of spontaneously hydrocephalic rats. Brains from control rats and spontaneously hydrocephalic rats of 12 months of age were used. The SCO sections were immunohistochemically processed with anti-TAp73 and anti-Reissner fibre (AFRU). The spontaneous hydrocephalus presents a decrease in the AFRU immunoreactive material in the SCO and an absence of RF. The anti-TAp73 was also present, slightly decreased, in the hydrocephalic SCO. AFRU and p73 bands were also detected in the CSF by western blot and six AFRU and p73 protein bands of a similar molecular weight were found in the CSF of the control rats. The number of AFRU and p73 bands was lower in the hydrocephalic rats than in the control rats. In conclusion, hydrocephalus produces a decrease in the secretions of the SCO and an absence of RF and a decrease in p73 and RF proteins in the CSF. PMID:19519738

  13. Spectral counting assessment of protein dynamic range in cerebrospinal fluid following depletion with plasma-designed immunoaffinity columns

    PubMed Central

    2011-01-01

    Background In cerebrospinal fluid (CSF), which is a rich source of biomarkers for neurological diseases, identification of biomarkers requires methods that allow reproducible detection of low abundance proteins. It is therefore crucial to decrease dynamic range and improve assessment of protein abundance. Results We applied LC-MS/MS to compare the performance of two CSF enrichment techniques that immunodeplete either albumin alone (IgYHSA) or 14 high-abundance proteins (IgY14). In order to estimate dynamic range of proteins identified, we measured protein abundance with APEX spectral counting method. Both immunodepletion methods improved the number of low-abundance proteins detected (3-fold for IgYHSA, 4-fold for IgY14). The 10 most abundant proteins following immunodepletion accounted for 41% (IgY14) and 46% (IgYHSA) of CSF protein content, whereas they accounted for 64% in non-depleted samples, thus demonstrating significant enrichment of low-abundance proteins. Defined proteomics experiment metrics showed overall good reproducibility of the two immunodepletion methods and MS analysis. Moreover, offline peptide fractionation in IgYHSA sample allowed a 4-fold increase of proteins identified (520 vs. 131 without fractionation), without hindering reproducibility. Conclusions The novelty of this study was to show the advantages and drawbacks of these methods side-to-side. Taking into account the improved detection and potential loss of non-target proteins following extensive immunodepletion, it is concluded that both depletion methods combined with spectral counting may be of interest before further fractionation, when searching for CSF biomarkers. According to the reliable identification and quantitation obtained with APEX algorithm, it may be considered as a cheap and quick alternative to study sample proteomic content. PMID:21906361

  14. A Hospital Based Study on Estimation of Adenosine Deaminase Activity (ADA) in Cerebrospinal Fluid (CSF) in Various Types of Meningitis

    PubMed Central

    Agarwal, Ashok Kumar; Bansal, Sonia; Nand, Vidya

    2014-01-01

    Objective: Tuberculosis kills 3.70 lakh patients in India every year,out of which 7-12 % are meningeal involvement. Delay in its diagnosis and initiation of treatment results in poor prognosis and squeal in up to 25% of cases. The aim of the present study is to look for a simple, rapid, cost effective, and fairly specific test in differentiating tubercular aetiology from other causes of meningitis. In the present study we measured the adenosine deaminase activity (ADA) in Cerebrospinal Fluid (CSF) of Tubercular Meningitis (TBM) and non-TBM patients. Methods: Fifty six patients attending hospital with symptoms and signs of meningitis were selected and divided into three groups: tubercular, pyogenic, and aseptic meningitis, depending upon the accepted criteria. CSF was drawn and ADA estimated. Results: Out of 32 tubercular patients, 28 had CSF-ADA at or above the cut-off value while four had below. Out of 24 non-tuberculous patients (pyogenic and aseptic meningitis), two aseptic meningitis (AM) patient had ADA levels at or above the cut-off value while 22 had below this value. Results of our study indicate that ADA level estimation in CSF is not only of considerable value in the diagnosis of TBM, CSF, and ADA level 10 U/L as a cut-off value with sensitivity 87.5% and specificity 83.33% and positive predictive value of the test was 87.5%.and 83.3% negative predictive value. Conclusion: It can be concluded that ADA estimation in CSF is not only simple, inexpensive and rapid but also fairly specific method for making a diagnosis of tuberculous aetiology in TBM, especially when there is a dilemma of differentiating the tuberculous aetiology from non-tuberculous ones. For this reason ADA estimation in TBM may find a place as a routine investigation. PMID:24701487

  15. Pharmacokinetics and effects of mannitol on hemodynamics, blood and cerebrospinal fluid electrolytes, and osmolality during intracranial surgery.

    PubMed

    Rudehill, A; Gordon, E; Ohman, G; Lindqvist, C; Andersson, P

    1993-01-01

    Fifteen patients who underwent surgery for intracranial tumors under general anesthesia were given mannitol (1 g/kg of body weight) over 30 min. Measurements of mannitol concentration, osmolality, and electrolytes were determined in blood and cerebrospinal fluid (CSF) samples collected over an 8-h period. Seven sets of hemodynamic observations and four sets of intracranial pressure (ICP) measurements were also made. Mannitol disappeared from plasma in a biexponential manner. The mean maximal plasma concentration was 5.91 mg/ml at the end of mannitol infusion and decreased to 0.58 mg/ml after 8 h. The plasma half-life for the distribution phase was 0.16 h and for the elimination phase was 2.44 h. The distribution volume was 17.0 L and total plasma clearance 87.4 ml/min. There were marked interindividual variations of mannitol concentration in the CSF. The mean CSF concentration at 8 h was 97.1 micrograms/ml, started to decline earlier in 10 of 12 patients, and never exceeded 12% of that in plasma. Osmolality in serum increased with a maximum at the end of mannitol infusion (from 292 +/- 7 mOsmol/kg to 310 +/- 14 mOsmol/kg; p < 0.01), whereas CSF osmolality was unchanged, thus giving rise to a positive blood-CSF osmotic gradient of at least 10 mOsmol/kg for about 30 min. At the end of the mannitol infusion, cardiac output and pulmonary capillary wedge pressure increased significantly, whereas the hematocrit decreased. ICP was observed in five patients for 45 min, and mannitol induced a mean reduction from 11 +/- 4 to 4 +/- 2 mm Hg (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8431668

  16. New experimental model of acute aqueductal blockage in cats: effects on cerebrospinal fluid pressure and the size of brain ventricles.

    PubMed

    Klarica, M; Oreskovi?, D; Bozi?, B; Vuki?, M; Butkovi?, V; Bulat, M

    2009-02-18

    It is generally assumed that cerebrospinal fluid (CSF) is secreted in the brain ventricles, and so after an acute blockage of the aqueduct of Sylvius an increase in the ventricular CSF pressure and dilation of isolated ventricles may be expected. We have tested this hypothesis in cats. After blocking the aqueduct, we measured the CSF pressure in both isolated ventricles and the cisterna magna, and performed radiographic monitoring of the cross-sectional area of the lateral ventricle. The complete aqueductal blockage was achieved by implanting a plastic cannula into the aqueduct of Sylvius through a small tunnel in the vermis of the cerebellum in the chloralose-anesthetized cats. After the reconstitution of the occipital bone, the CSF pressure was measured in the isolated ventricles via a plastic cannula implanted in the aqueduct of Sylvius and in the cisterna magna via a stainless steel cannula. During the following 2 h, the CSF pressures in the isolated ventricles and cisterna magna were identical to those in control conditions. We also monitored the ventricular cross-sectional area by means of radiography for 2 h after the aqueductal blockage and failed to observe any significant changes. When mock CSF was infused into isolated ventricles to imitate the CSF secretion, the gradient of pressure between the ventricle and cisterna magna developed, and disappeared as soon as the infusion was terminated. However, when mock CSF was infused into the cisterna magna at various rates, the resulting increased subarachnoid CSF pressure was accurately transmitted across the brain parenchyma into the CSF of isolated ventricles. The lack of the increase in the CSF pressure and ventricular dilation during 2 h of aqueductal blockage suggests that aqueductal obstruction by itself does not lead to development of hypertensive acute hydrocephalus in cats. PMID:19111908

  17. Volumetric analysis of cerebrospinal fluid and brain parenchyma in a patient with hydranencephaly and macrocephaly--case report.

    PubMed

    Radoš, Milan; Klarica, Marijan; Mu?i?-Puci?, Branka; Niki?, Ines; Raguž, Marina; Galkowski, Valentina; Mandi?, Dora; Oreškovi?, Darko

    2014-08-28

    The aim of this study was to perform for the first time the intracranial volumetric analysis of cerebrospinal fluid (CSF) and brain parenchyma in the supratentorial and infratentorial space in a 30-year-old female patient with hydranencephaly and macrocephaly. A head scan performed using a 3T magnetic resonance was followed by manual segmentation of the brain parenchyma and CSF on T2 coronal brain sections. The volume of CSF and brain parenchyma was measured separately for the supratentorial and infratentorial space. The total volume of the intracranial space was 3645.5 cm3. In the supratentorial space, the volume of CSF was 3375.2 cm3 and the volume of brain parenchyma was 80.3 cm3. In the infratentorial space, the volume of CSF was 101.3 cm3 and the volume of the brain parenchyma was 88.7 cm3. In the supratentorial space, there was severe malacia of almost all brain parenchyma with no visible remnants of the choroid plexuses. Infratentorial structures of the brainstem and cerebellum were hypoplastic but completely developed. Since our patient had no choroid plexuses in the supratentorial space and no obstruction between dural sinuses and CSF, development of hydrocephalus and macrocephaly cannot be explained by the classic hypothesis of CSF physiology with secretion, unidirectional circulation, and absorption as its basic postulates. However, the origin and turnover of the enormous amount of intracranial CSF volume, at least 10-fold larger than normal, and the mechanisms of macroencephaly development could be elucidated by the new hypothesis of CSF physiology recently published by our research team. PMID:25165052

  18. Seasonal variation of serotonin turnover in human cerebrospinal fluid, depressive symptoms and the role of the 5-HTTLPR

    PubMed Central

    Luykx, J J; Bakker, S C; van Geloven, N; Eijkemans, M J C; Horvath, S; Lentjes, E; Boks, M P M; Strengman, E; DeYoung, J; Buizer-Voskamp, J E; Cantor, R M; Lu, A; van Dongen, E P A; Borgdorff, P; Bruins, P; Kahn, R S; Ophoff, R A

    2013-01-01

    Studying monoaminergic seasonality is likely to improve our understanding of neurobiological mechanisms underlying season-associated physiological and pathophysiological behavior. Studies of monoaminergic seasonality and the influence of the serotonin-transporter-linked polymorphic region (5-HTTLPR) on serotonin seasonality have yielded conflicting results, possibly due to lack of power and absence of multi-year analyses. We aimed to assess the extent of seasonal monoamine turnover and examined the possible involvement of the 5-HTTLPR. To determine the influence of seasonality on monoamine turnover, 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were measured in the cerebrospinal fluid of 479 human subjects collected during a 3-year period. Cosine and non-parametric seasonal modeling were applied to both metabolites. We computed serotonin (5-HT) seasonality values and performed an association analysis with the s/l alleles of the 5-HTTLPR. Depressive symptomatology was assessed using the Beck Depression Inventory-II. Circannual variation in 5-HIAA fitted a spring-peak cosine model that was significantly associated with sampling month (P=0.0074). Season of sampling explained 5.4% (P=1.57 × 10?7) of the variance in 5-HIAA concentrations. The 5-HTTLPR s-allele was associated with increased 5-HIAA seasonality (standardized regression coefficient=0.12, P=0.020, N=393). 5-HIAA seasonality correlated with depressive symptoms (Spearman's rho=0.13, P=0.018, N=345). In conclusion, we highlight a dose-dependent association of the 5-HTTLPR with 5-HIAA seasonality and a positive correlation between 5-HIAA seasonality and depressive symptomatology. The presented data set the stage for follow-up in clinical populations with a role for seasonality, such as affective disorders. PMID:24105442

  19. Microscopic Particles in Two Fractions of Fresh Cerebrospinal Fluid in Twins with Schizophrenia or Bipolar Disorder and in Healthy Controls

    PubMed Central

    Johansson, Viktoria; Nybom, Rolf; Wetterberg, Lennart; Hultman, Christina M.; Cannon, Tyrone D.; Johansson, Anette G. M.; Ekman, Carl Johan; Landén, Mikael

    2012-01-01

    Background Using scanning electron microscopy, microscopic structures have been identified in fresh cerebrospinal fluid (CSF) in patients with schizophrenia and bipolar disorder, but only rarely in control subjects. However, it has not been determined whether these microscopic particles represent state or trait markers, i.e. if their presence is related to clinical manifestations of the disease or if they also can be found in as yet asymptomatic individuals with a genetic liability. This question can be addressed by studying twins discordant or concordant for schizophrenia or bipolar disorder. Methodology/Principal Findings We investigated microscopic structures in CSF in 102 individuals: 21 monozygotic and 16 dizygotic twins affected or not affected with schizophrenia, schizoaffective disorder or bipolar disorder and in 65 healthy singleton controls. A first and a second fraction of CSF was freshly applied on filters and examined by scanning electron microscopy technique. Spherical particles with lipid appearance averaging between 0.1 to 8.0 µm in diameter were detected in the center of the filter as well as located in the margins of larger aggregates binding in a viscous state. Structures were found in 12 of 17 probands, 5 of 12 healthy co-twins and 3 of 73 healthy controls. Thus, a positive microscopic finding significantly increased the likelihood of belonging to the proband group (OR?=?48, 95% CL: 8.2–550, p<0.0001) and the co-twin-group (OR?=?16, 95% CL: 2.0–218, p?=?0.006). Age, sex, history of alcohol abuse or anxiety syndrome, somatic disorder and markers of acute inflammatory activity did not account for group differences; nor did exposure to psychotropic medication. Conclusion Presence of microscopic particles in CSF may possibly reflect trait dependent genetic or environmental vulnerability in patients with schizophrenia, schizoaffective disorder or bipolar disorder. PMID:23049916

  20. Autoantibody Profiling on Human Proteome Microarray for Biomarker Discovery in Cerebrospinal Fluid and Sera of Neuropsychiatric Lupus

    PubMed Central

    Song, Guang; Li, Ping; Shan, Qiang; Zhang, Xuan; Zhang, Fengchun; Zhu, Heng; Wu, Lin; Li, Yongzhe

    2015-01-01

    Autoantibodies in cerebrospinal fluid (CSF) from patients with neuropsychiatric systemic lupus erythematosus (NPSLE) may be potential biomarkers for prediction, diagnosis, or prognosis of NPSLE. We used a human proteome microarray with~17,000 unique full-length human proteins to investigate autoantibodies associated with NPSLE. Twenty-nine CSF specimens from 12 NPSLE, 7 non-NPSLE, and 10 control (non-systemic lupus erythematosus)patients were screened for NPSLE-associated autoantibodies with proteome microarrays. A focused autoantigen microarray of candidate NPSLE autoantigens was applied to profile a larger cohort of CSF with patient-matched sera. We identified 137 autoantigens associated with NPSLE. Ingenuity Pathway Analysis revealed that these autoantigens were enriched for functions involved in neurological diseases (score = 43).Anti-proliferating cell nuclear antigen (PCNA) was found in the CSF of NPSLE and non-NPSLE patients. The positive rates of 4 autoantibodies in CSF specimens were significantly different between the SLE (i.e., NPSLE and non-NPSLE) and control groups: anti-ribosomal protein RPLP0, anti-RPLP1, anti-RPLP2, and anti-TROVE2 (also known as anti-Ro/SS-A). The positive rate for anti-SS-A associated with NPSLE was higher than that for non-NPSLE (31.11% cf. 10.71%; P = 0.045).Further analysis showed that anti-SS-A in CSF specimens was related to neuropsychiatric syndromes of the central nervous system in SLE (P = 0.009). Analysis with Spearman’s rank correlation coefficient indicated that the titers of anti-RPLP2 and anti-SS-A in paired CSF and serum specimens significantly correlated. Human proteome microarrays offer a powerful platform to discover novel autoantibodies in CSF samples. Anti-SS-A autoantibodies may be potential CSF markers for NPSLE. PMID:25954975

  1. A review article on the diagnosis and treatment of cerebrospinal fluid fistulas and dural tears occurring during spinal surgery

    PubMed Central

    Epstein, Nancy E.

    2013-01-01

    Background: In spinal surgery, cerebrospinal fluid (CSF) fistulas attributed to deliberate dural opening (e.g., for tumors, shunts, marsupialization of cysts) or inadvertent/traumatic dural tears (DTs) need to be readily recognized, and appropriately treated. Methods: During spinal surgery, the dura may be deliberately opened to resect intradural lesions/tumors, to perform shunts, or to open/marsupialize cysts. DTs, however, may inadvertently occur during primary, but are seen more frequently during revision spinal surgery often attributed to epidural scarring. Other etiologies of CSF fistulas/DTs include; epidural steroid injections, and resection of ossification of the posterior longitudinal ligament (OPLL) or ossification of the yellow ligament (OYL). Whatever the etiology of CSF fistulas or DTs, they must be diagnosed utilizing radioisotope cisternography (RIC), magnetic resonance imaging (MRI), computed axial tomography (CT) studies, and expeditiously repaired. Results: DTs should be repaired utilizing interrupted 7-0 Gore-Tex (W.L. Gore and Associates Inc., Elkton, MD, USA) sutures, as the suture itself is larger than the needle; the larger suture occludes the dural puncture site. Closure may also include muscle patch grafts, dural patches/substitutes (bovine pericardium), microfibrillar collagen (Duragen: Integra Life Sciences Holdings Corporation, Plainsboro, NJ), and fibrin glues or dural sealants (Tisseel: Baxter Healthcare Corporation, Deerfield, IL, USA). Only rarely are lumbar drains and wound-peritoneal and/or lumboperitoneal shunts warranted. Conclusion: DTs or CSF fistulas attributed to primary/secondary spinal surgery, trauma, epidural injections, OPLL, OYL, and other factors, require timely diagnosis (MRI/CT/Cisternography), and appropriate reconstruction. PMID:24163783

  2. IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in first-episode schizophrenia.

    PubMed

    Severance, Emily G; Gressitt, Kristin L; Alaedini, Armin; Rohleder, Cathrin; Enning, Frank; Bumb, J Malte; Müller, Juliane K; Schwarz, Emanuel; Yolken, Robert H; Leweke, F Markus

    2015-02-01

    Schizophrenia is a complex brain disorder that may be accompanied by idiopathic inflammation. Classic central nervous system (CNS) inflammatory disorders such as viral encephalitis or multiple sclerosis can be characterized by incongruent serum and cerebrospinal fluid (CSF) IgG due in part to localized intrathecal synthesis of antibodies. The dietary antigens, wheat gluten and bovine milk casein, can induce a humoral immune response in susceptible individuals with schizophrenia, but the correlation between the food-derived serological and intrathecal IgG response is not known. Here, we measured IgG to wheat gluten and bovine milk casein in matched serum and CSF samples from 105 individuals with first-episode schizophrenia (n=75 antipsychotic-naïve), and 61 controls. We found striking correlations in the levels of IgG response to dietary proteins between serum and CSF of schizophrenia patients, but not controls (schizophrenia, R(2)=0.34-0.55, p?0.0001; controls R(2)=0.05-0.06, p>0.33). A gauge of blood-CSF barrier permeability and CSF flow rate, the CSF-to-serum albumin ratio, was significantly elevated in cases compared to controls (p?0.001-0.003). Indicators of intrathecal IgG production, the CSF IgG index and the specific Antibody Index, were not significantly altered in schizophrenia compared to controls. Thus, the selective diffusion of bovine milk casein and wheat gluten antibodies between serum and CSF in schizophrenia may be the function of a low-level anatomical barrier dysfunction or altered CSF flow rate, which may be transient in nature. PMID:25241021

  3. Biomarkers of mild traumatic brain injury in cerebrospinal fluid and blood.

    PubMed

    Zetterberg, Henrik; Smith, Douglas H; Blennow, Kaj

    2013-04-01

    Mild traumatic brain injury (TBI), which is defined as a head trauma resulting in a brief loss of consciousness and/or alteration of mental state, is usually benign, but occasionally causes persistent and sometimes progressive symptoms. Whether a threshold for the amount of brain injury and/or individual vulnerability might contribute to the development of these long-term consequences is unknown. Furthermore, reliable diagnostic methods that can establish whether a blow to the head has affected the brain (and in what way) are lacking. In this Review, we discuss potential biomarkers of injury to different structures and cell types in the CNS that can be detected in body fluids. We present arguments in support of the need for further development and validation of such biomarkers, and for their use in assessing patients with head trauma in whom the brain might have been affected. Specifically, we focus on the need for such biomarkers in the management of sports-related concussion, the most common cause of mild TBI in young individuals, to prevent long-term neurological sequelae due to concussive or subconcussive blows to the head. PMID:23399646

  4. Stacking, derivatization, and separation by capillary electrophoresis of amino acids from cerebrospinal fluids.

    PubMed

    Chang, Po-Ling; Chiu, Tai-Chia; Chang, Huan-Tsung

    2006-05-01

    This paper describes the in-column derivatization, stacking, and separation of amino acids by CE in conjunction with light-emitting diode-induced fluorescence using naphthalene-2,3-dicarboxaldehyde (NDA). According to the relative electrophoretic mobilities and the migration direction in tetraborate solution (pH 9.3), the injection order is cyanide, then amino acids, then NDA. Once poly(ethylene oxide) (PEO) migrates through the capillary under EOF, the amino acid.NDA derivatives, amino acids, and CN- ions migrating against the EOF enter the PEO zone. As a result of increases in viscosity and possible interactions with PEO molecules, the reagents/analytes slow down such that they become stacked at the boundary. In comparison with the off-column approach to the analysis of amino acids, our proposed method provides a lower degree of interference from polymeric NDA compounds and other side products. As a result, the plot of the peak height as a function of gamma-aminobutyric acid (GABA) concentration is linear over the range from 10(-5) to 10(-8) M, with the LOD being 4 nM. We demonstrate the diagnostic potential of this approach for the determination of amino acids, including GABA and glutamine, in biological samples through the analysis of large volumes of cerebral spinal fluids without the need for sample pretreatment. PMID:16703625

  5. Biomarkers of mild traumatic brain injury in cerebrospinal fluid and blood

    PubMed Central

    Zetterberg, Henrik; Smith, Douglas H.; Blennow, Kaj

    2014-01-01

    Mild traumatic brain injury (TBI), which is defined as a head trauma resulting in a brief loss of consciousness and/or alteration of mental state, is usually benign, but occasionally causes persistent and sometimes progressive symptoms. Whether a threshold for the amount of brain injury and/or individual vulnerability might contribute to the development of these long-term consequences is unknown. Furthermore, reliable diagnostic methods that can establish whether a blow to the head has affected the brain (and in what way) are lacking. In this Review, we discuss potential biomarkers of injury to different structures and cell types in the CNS that can be detected in body fluids. We present arguments in support of the need for further development and validation of such biomarkers, and for their use in assessing patients with head trauma in whom the brain might have been affected. Specifically, we focus on the need for such biomarkers in the management of sports-related concussion, the most common cause of mild TBI in young individuals, to prevent long-term neurological sequelae due to concussive or subconcussive blows to the head. PMID:23399646

  6. A validated LC-MS/MS assay for quantification of 24(S)-hydroxycholesterol in plasma and cerebrospinal fluid[S

    PubMed Central

    Sidhu, Rohini; Jiang, Hui; Farhat, Nicole Y.; Carrillo-Carrasco, Nuria; Woolery, Myra; Ottinger, Elizabeth; Porter, Forbes D.; Schaffer, Jean E.; Ory, Daniel S.; Jiang, Xuntian

    2015-01-01

    24(S)-hydroxycholesterol [24(S)-HC] is a cholesterol metabolite that is formed almost exclusively in the brain. The concentrations of 24(S)-HC in cerebrospinal fluid (CSF) and/or plasma might be a sensitive marker of altered cholesterol metabolism in the CNS. A highly sensitive 2D-LC-MS/MS assay was developed for the quantification of 24(S)-HC in human plasma and CSF. In the development of an assay for 24(S)-HC in CSF, significant nonspecific binding of 24(S)-HC was observed and resolved with the addition of 2.5% 2-hydroxypropyl-?-cyclodextrin (HP-?-CD) into CSF samples. The sample preparation consists of liquid-liquid extraction with methyl-tert-butyl ether and derivatization with nicotinic acid. Good linearity was observed in a range from 1 to 200 ng/ml and from 0.025 to 5 ng/ml, for plasma and CSF, respectively. Acceptable precision and accuracy were obtained for concentrations over the calibration curve ranges. Stability of 24(S)-HC was reported under a variety of storage conditions. This method has been successfully applied to support a National Institutes of Health-sponsored clinical trial of HP-?-CD in Niemann-Pick type C1 patients, in which 24(S)-HC is used as a pharmacodynamic biomarker. PMID:25866316

  7. Influence of early cerebrospinal fluid-guided diagnosis and early high-dose corticosteroid therapy on ocular outcomes of Vogt–Koyanagi–Harada disease

    Microsoft Academic Search

    Masaru Miyanaga; Tatushi Kawaguchi; Kentaro Shimizu; Kazunori Miyata; Manabu Mochizuki

    2007-01-01

    Purpose  To evaluate the importance of early cerebrospinal fluid (CSF)-guided diagnosis and early high-dose corticosteroid therapy\\u000a on the complications and visual prognosis of Vogt–Koyanagi–Harada (VKH) disease.\\u000a \\u000a \\u000a \\u000a Patients and methods  Charts from patients with VKH disease who had been seen at Tokyo Medical and Dental University Hospital and Miyata Eye Hospital\\u000a between 1994 and 2002 were retrospectively reviewed. The patients were classified into

  8. Cerebrospinal Fluid (CSF) CD8+ T-Cells That Express Interferon-Gamma Contribute to HIV Associated Neurocognitive Disorders (HAND)

    PubMed Central

    Schrier, Rachel D.; Hong, Suzi; Crescini, Melanie; Ellis, Ronald; Pérez-Santiago, Josué; Spina, Celsa; Letendre, Scott

    2015-01-01

    Background HIV associated neurocognitive disorders (HAND) continue to affect cognition and everyday functioning despite anti-retroviral treatment (ART). Previous studies focused on mechanisms related to monocyte/macrophage mediated inflammation. However, in the ART era, there is increasing evidence for the involvement of CD8+ T-cells in CNS pathogenesis. Methods To investigate the relationship between T-cell responses and neurocognitive impairment (NCI), cerebrospinal fluid (CSF) and peripheral blood CD4+ and CD8+ T-cell intracellular cytokine (IFN?, IL-2, TNF?) and lytic marker (CD107a) expression were assessed in HIV infected subjects who underwent comprehensive neurocognitive (NC) evaluation and either initiated or changed ART. Results Data were collected from 31 participants at 70 visits. The frequency of cytokine expressing T-cells in CSF was significantly higher than in peripheral blood for CD4+T-cells: TNF?, IL-2, IFN? and CD8+T-cells: IL-2 and IFN?. Analysis of T-cell activity and NCI as a function of CSF HIV RNA levels suggested a general association between NCI, high CSF CD8+ (but not CD4+T-cell) cytokine expression and CSF HIV RNA <103 copies/ml (p<0.0001). Specifically, CSF CD8+ T-cell IFN? expression correlated with severity of NCI (r = 0.57, p = 0.004). Multivariable analyses indicated that CSF CD8+T-cell IFN? and myeloid activation (CD163) contributed equally and independently to cognitive status and a composite variable produced the strongest correlation with NCI (r = 0.83, p = 0.0001). In contrast, CD8+ cytolytic activity (CD107a expression) was negatively correlated with NCI (p = 0.05) but was dependent on CD4 levels >400/?l and low CSF HIV RNA levels (<103 copies/ml). In our longitudinal analysis of 16 subjects, higher CSF CD8+IFN? expression at baseline predicted NC decline at follow-up (p = 0.02). Severity of NCI at follow-up correlated with level of residual HIV RNA in CSF. Conclusions Presence of IFN? expressing CD8+ T-cells, absence of cytolytic CD8+ T-cells, high myeloid activation, and failure of ART to suppress HIV replication in CSF contribute to increased risk of HAND. PMID:25719800

  9. Cerebrospinal fluid levels of MMP-2, 7, and 9 are elevated in association with human immunodeficiency virus dementia.

    PubMed

    Conant, K; McArthur, J C; Griffin, D E; Sjulson, L; Wahl, L M; Irani, D N

    1999-09-01

    Pathological evidence suggests that alterations of the blood-brain barrier (BBB) may occur in association with human immunodeficiency virus (HIV) dementia (HIVD). Increased BBB permeability could contribute to the development of dementia by facilitating the entry of activated and infected monocytes, as well as potentially toxic serum proteins, into the central nervous system. One mechanism by which BBB permeability may be altered is through increased activity of select matrix metalloproteinases (MMPs). In the present study, we examined the possibility that MMPs that target critical BBB proteins, including laminin, entactin, and collagen type IV, are elevated in the cerebrospinal fluid (CSF) of patients with HIVD. We also examined the possibility that such MMPs could be produced by brain-derived cells, and that MMP production by these cells might be increased by tumor necrosis factor-alpha, an inflammatory cytokine that is produced by HIV-infected monocytes/microglia and is elevated in HIVD. By using western blot and enzyme-linked immunosorbent assay, we observed that CSF levels of pro-MMP-2 and pro-MMP-7 were increased in association with HIVD. In addition, through the use of gelatin substrate zymography, a sensitive functional assay for MMP-2 and MMP-9, we observed that MMP-2 or pro-MMP-9 activity was more frequently detectable in the CSF of individuals with HIV dementia (9/16) than in the CSF from either nondemented seropositive (2/11) or seronegative (0/11) controls. Although the presence of MMPs in the serum could contribute to elevated levels in the CSF, we also show that brain-derived cells release MMP-2, 7, and 9, and that such release is increased after their stimulation with tumor necrosis factor-alpha. Together, these results suggest that elevated CSF levels of select MMPs may reflect immune activation within the central nervous system. They also suggest that further studies may be warranted to determine whether these proteins may play a role in the development of symptomatic neurological disease. PMID:10482270

  10. In vitro effects of fetal rat cerebrospinal fluid on viability and neuronal differentiation of PC12 cells

    PubMed Central

    2012-01-01

    Background Fetal cerebrospinal fluid (CSF) contains many neurotrophic and growth factors and has been shown to be capable of supporting viability, proliferation and differentiation of primary cortical progenitor cells. Rat pheochromocytoma PC12 cells have been widely used as an in vitro model of neuronal differentiation since they differentiate into sympathetic neuron-like cells in response to growth factors. This study aimed to establish whether PC12 cells were responsive to fetal CSF and therefore whether they might be used to investigate CSF physiology in a stable cell line lacking the time-specific response patterns of primary cells previously described. Methods In vitro assays of viability, proliferation and differentiation were carried out after incubation of PC12 cells in media with and without addition of fetal rat CSF. An MTT tetrazolium assay was used to assess cell viability and/or cell proliferation. Expression of neural differentiation markers (MAP-2 and ?-III tubulin) was determined by immunocytochemistry. Formation and growth of neurites was measured by image analysis. Results PC12 cells differentiate into neuronal cell types when exposed to bFGF. Viability and cell proliferation of PC12 cells cultured in CSF-supplemented medium from E18 rat fetuses were significantly elevated relative to the control group. Neuronal-like outgrowths from cells appeared following the application of bFGF or CSF from E17 and E19 fetuses but not E18 or E20 CSF. Beta-III tubulin was expressed in PC12 cells cultured in any media except that supplemented with E18 CSF. MAP-2 expression was found in control cultures and in those with E17 and E19 CSF. MAP2 was located in neurites except in E17 CSF when the whole cell was positive. Conclusions Fetal rat CSF supports viability and stimulates proliferation and neurogenic differentiation of PC12 cells in an age-dependent way, suggesting that CSF composition changes with age. This feature may be important in vivo for the promotion of normal brain development. There were significant differences in the effects on PC12 cells compared to primary cortical cells. This suggests there is an interaction in vivo between developmental stage of cells and the composition of CSF. The data presented here support an important, perhaps driving role for CSF composition, specifically neurotrophic factors, in neuronal survival, proliferation and differentiation. The effects of CSF on PC12 cells can thus be used to further investigate the role of CSF in driving development without the confounding issues of using primary cells. PMID:22494846

  11. Dynamic Cerebrospinal Fluid Flow on MRI in Cortical Cerebellar Atrophy and Multiple System Atrophy-cerebellar Type.

    PubMed

    Fukui, Yusuke; Hishikawa, Nozomi; Sato, Kota; Kono, Syoichiro; Matsuzono, Kosuke; Nakano, Yumiko; Ohta, Yasuyuki; Yamashita, Toru; Deguchi, Kentaro; Abe, Koji

    2015-01-01

    Objective The purpose of this study was to examine a new MRI technology, dynamic cerebrospinal fluid (CSF) flow, to examine sporadic cerebellar ataxia patients with cortical cerebellar atrophy (CCA) and multiple system atrophy-cerebellar type (MSA-C). Methods Nine CCA patients (3 men and 6 women; mean age: 64.2±6.9 years) and 31 MSA-C patients (13 men and 18 women; mean age: 62.7±6.8 years) were examined by a dynamic CSF flow analysis. All CSF flow data were evaluated by phase contrast-MRI using a 1.5T MRI scanner. The CSF flow was calculated by 15 images in the equidistant MRI sequence which was taken through a cardiac cycle. Results Compared with the CCA patients, the absolute values of the mean velocity of the MSA-C patients were significantly reduced at time points 5 (CCA, 0.24±0.14 cm/s; MSA-C, 0.13±0.11 cm/s; (*) p<0.05) and 13 (CCA, -0.60±0.37 cm/s; MSA-C, -0.31±0.17 cm/s; (**) p<0.01). Significant correlations in Spearman's rank correlation coefficient were also found in MSA-C patients between the disease duration and the difference between the maximum and minimum velocities (Vheight) (r=-0.429, (*) p<0.05), the minimum velocity of the CSF (Vmin) (r=0.486, (**) p<0.01) or the length of the minor axis of the pons (r=-0.529, (**) p<0.01). The linear regressions between the disease duration and Vheight or Vmin revealed a significant strong correlation only in the MSA-C patients. Conclusion The present CSF flow study showed for the first time that Vheight and Vmin revealed good correlations with the disease duration in the MSA-C patients. Furthermore, the velocity of the prepontine CSF flow tended to decrease in the MSA-C patients compared with the CCA patients, suggesting that this particular CSF flow analysis may be a new surrogate marker for differentiating both types of cerebellar ataxia. PMID:26179524

  12. Paenibacillus provencensis sp. nov., isolated from human cerebrospinal fluid, and Paenibacillus urinalis sp. nov., isolated from human urine.

    PubMed

    Roux, Véronique; Fenner, Lukas; Raoult, Didier

    2008-03-01

    Gram-negative, spore-forming rods were isolated from a human urine sample (strain 5402403(T)) and a human cerebrospinal fluid sample (strain 4401170(T)). Based on genotypic characteristics, these strains belonged to the genus Paenibacillus and were closely related. Phylogenetic analysis based on 16S rRNA gene sequence comparison showed that they clustered with Paenibacillus massiliensis 2301065(T) (95.9 and 94.3 % 16S rRNA gene sequence similarity, respectively, for strains 5402403(T) and 4401170(T)), Paenibacillus illinoisensis NRRL NRS-61356(T) (90.6 and 93.8 %), Paenibacillus xylanilyticus XIL14(T) (95.3 and 95.4 %), Paenibacillus barcinonensis BP-23(T) (94.3 and 94.0 %), Paenibacillus pabuli NCIMB 12781(T) (89.1 and 92.3 %) and Paenibacillus amylolyticus NRRL NRS-290(T) (94.2 and 93.8 %). The predominant fatty acids were 15 : 0 anteiso (49.0 and 55.3 %, respectively, for strains 5402403(T) and 4401170(T)), 16 : 0 iso (15.4 and 13.5 %), 16 : 0 (7.6 and 3.6 %), 15 : 0 (6.3 and 2.8 %), 17 : 0 anteiso (5.7 and 7.5 %), 14 : 0 iso (4.1 and 2.7 %) and 15 : 0 iso (4.1 and 3.4 %). 16S rRNA gene sequence similarity between strain 4401170(T) and strain 5402403(T) was 98.4 %, but the DNA-DNA reassociation rate between the two strains was 53.2 %. So, considering the recommendations of the ad hoc committee, they do not belong to the same species. On the basis of phenotypic data and genotypic inference, it is proposed that the strains should be assigned to the novel species Paenibacillus urinalis sp. nov. (type strain 5402403(T) =CIP 109357(T) =CCUG 53521(T)) and Paenibacillus provencensis sp. nov. (type strain 4401170(T) =CIP 109358(T) =CCUG 53519(T)). PMID:18319478

  13. Low levels of cerebrospinal fluid complement 3 and factor H predict faster cognitive decline in mild cognitive impairment

    PubMed Central

    2014-01-01

    Introduction Alzheimer’s disease (AD) is characterized by the deposition of tau and amyloid in the brain. Although the core cerebrospinal fluid (CSF) AD biomarkers amyloid ? peptide 1–42 (A?1–42), total tau (t-tau) and phosphorylated tau 181 (p-tau181) show good diagnostic sensitivity and specificity, additional biomarkers that can aid in preclinical diagnosis or better track disease progression are needed. Activation of the complement system, a pivotal part of inflammation, occurs at very early stages in the AD brain. Therefore, CSF levels of complement proteins that could be linked to cognitive and structural changes in AD may have diagnostic and prognostic value. Methods Using xMAP® technology based assays we measured complement 3 (C3) and factor H (FH) in the CSF of 110 controls (CN), 187 mild cognitive impairment (MCI) and 92 AD subjects of the AD Neuroimaging Initiative (ADNI) at baseline. All ADNI participants underwent clinical follow-up at 12 month intervals and MCI subjects had additional visits at 6 and 18 months. The association between CSF biomarkers and different outcome measures were analyzed using Cox proportional hazard models (conversion from MCI to AD), logistic regression models (classification of clinical groups) and mixed-effects models adjusted for age, gender, education, t-tau/A?1–42 and APOE ?4 presence (baseline and longitudinal association between biomarkers and cognitive scores). Results Although no association was found between the complement proteins and clinical diagnosis or cognitive measures, lower levels of C3 (??=??0.12, p?=?0.041) and FH (??=??0.075, p?=?0.041) were associated with faster cognitive decline in MCI subjects as measured by the AD Assessment Scale-cognitive subscale (ADAS-Cog) test. Furthermore, lower FH levels were associated with larger lateral ventricular volume (p?=?0.024), which is indicative of brain atrophy. Conclusions Our study confirms a lack of suitability of CSF C3 and FH as diagnostic biomarkers of AD, but points to their modest potential as prognostic biomarkers and therapeutic targets in cognitively impaired patients. PMID:25478014

  14. CXCL13 and neopterin concentrations in cerebrospinal fluid of patients with Lyme neuroborreliosis and other diseases that cause neuroinflammation

    PubMed Central

    2014-01-01

    Background Laboratory diagnosis of Lyme neuroborreliosis (LNB) is partly based on the detection of intrathecal Borrelia burgdorferi–specific antibody production (increased antibody index (AI)). However, AI can be negative in patients with early LNB and, conversely, can remain elevated for months after antibiotic treatment. Recent studies suggested that the chemokine CXCL13 in the cerebrospinal fluid (CSF) is a biomarker for active LNB. Also, CSF neopterin-level determination has been used to assess the degree of neuroinflammation in a wide variety of diseases. Methods CXCL13 concentrations were analyzed in CSF samples of 366 retrospectively identified individuals. The samples represented pretreatment LNB (38 patients), non-LNB comparison patients, tick-borne encephalitis, central nervous system (CNS) varicella zoster virus infection, CNS herpes simplex virus infection, CNS HHV6 infection, CNS enterovirus infection, and untreated neurosyphilis. The panel included also samples from patients with multiple sclerosis and other neuroinflammatory conditions. Of the LNB patients, 24 posttreatment CSF samples were available for CXCL13 analysis. Neopterin concentrations were determined in a subset of these samples. Results The CXCL13 concentrations in CSF samples of untreated LNB patients were significantly higher (median, 6,480 pg/ml) than the concentrations in the non-LNB group (median, <7.8 pg/ml), viral CNS infection samples (median, <7.8 pg/ml), or samples from patients with noninfectious neuroinflammatory conditions (median, <7.8 pg/ml). The use of cut-off 415 pg/ml led to a sensitivity of 100% and specificity of 99.7% for the diagnosis of LNB in these samples. CSF CXCL13 median concentrations declined significantly from 16,770 pg/ml before to 109 pg/ml after the treatment. CSF neopterin concentration was significantly higher among the untreated LNB patients than in the non-LNB group. The use of neopterin concentration 10.6 nM as the cut-off led to a sensitivity of 88.6% and a specificity of 65.0% for the diagnosis of LNB. The CSF neopterin concentrations decreased statistically significantly with the treatment. Conclusions These results clearly indicate that highly elevated CSF CXCL13 levels are strongly associated with untreated LNB. CXCL13 outperformed neopterin and appears to be an excellent biomarker in differentiating LNB from viral CNS infections and from other neuroinflammatory conditions. PMID:24920219

  15. Clinical relevance of specific T-cell activation in the blood and cerebrospinal fluid of patients with mild Alzheimer's disease.

    PubMed

    Lueg, Gero; Gross, Catharina C; Lohmann, Hubertus; Johnen, Andreas; Kemmling, Andre; Deppe, Michael; Groger, Julia; Minnerup, Jens; Wiendl, Heinz; Meuth, Sven G; Duning, Thomas

    2015-01-01

    In Alzheimer's disease, the contribution of inflammation is still controversially discussed. The aim of this study was to identify a particular immune profile in the peripheral blood (PB) and cerebrospinal fluid (CSF) in patients with mild Alzheimer's disease (mAD) and mild cognitive impairment (MCI) and its potential functional relevance and association with neurodegeneration. A total of 88 patients with cognitive decline (54 mAD, 19 MCI, and 15 other dementias) were included in this study and compared with a group of younger (mean age, 31.3 years) and older (mean age, 68.9 years) healthy volunteers. Patients underwent detailed neurologic and neuropsychological examination, magnetic resonance imaging including voxel-based morphometry of gray matter, voxel-based diffusion tensor imaging, and white matter lesion volumetry, and PB and CSF analysis including multiparameter flow cytometry. Multiparameter flow cytometry revealed that proportions of activated HLA-DR positive CD4(+) and CD8(+) T-cells were slightly and significantly increased in the PB of MCI and mAD patients, respectively, when compared with healthy elderly controls but not in patients with other dementias. Although only a slight enhancement of the proportion of activated CD4(+) T-cells was observed in the CSF of both MCI and mAD patients, the proportion of activated CD8(+) T-cells was significantly increased in the CSF of mAD patients when compared with healthy elderly individuals. A slight increase in the proportion of activated CD8(+) T-cells was also observed in the intrathecal compartment of MCI patients. Activation of cytotoxic CD8(+) T-cells was considerably related to AD-typical neuropsychological deficits. Voxel-based regression analysis revealed a significant correlation between CD8(+) T-cell activation and microstructural tissue damage within parahippocampal areas as assessed by diffusion tensor imaging. Taken together, peripheral and intrathecal CD8(+) T-cell activation in mAD was significantly different from other dementias, suggesting a specific adaptive immune response. Lymphocyte activation seems to have a clinical impact because levels of activated CD8(+) T-cells were correlated with clinical and structural markers of AD pathology. PMID:25277040

  16. Measles antibodies, ?-? light chain distribution and immunoglobulins in serum, cerebrospinal fluid and brain of a patient affected with multiple sclerosis

    Microsoft Academic Search

    F. Bollengier; A. Mahler; G. Clinet

    1981-01-01

    The serum, cerebrospinal (CSF) and brain of a patient (NAG) affected with multiple sclerosis (MS) were examined for measles antibodies with CF and HI techniques, and the ?-? light chain ratios of all samples available were evaluated. ?-? populations of the matched serum, CSF and brain specimens were all ?-predominant and in agreement with each other; the light chain distribution

  17. A Pilot Trial of Pioglitazone HCl and Tretinoin in ALS: Cerebrospinal Fluid Biomarkers to Monitor Drug Efficacy and Predict Rate of Disease Progression

    PubMed Central

    Levine, Todd D.; Bowser, Robert; Hank, Nicole C.; Gately, Stephen; Stephan, Dietrich; Saperstein, David S.; Van Keuren-Jensen, Kendall

    2012-01-01

    Objectives. To determine if therapy with pioglitazone HCl and tretinoin could slow disease progression in patients with ALS. Levels of tau and pNFH in the cerebrospinal fluid were measured to see if they could serve as prognostic indicators. Methods. 27 subjects on stable doses of riluzole were enrolled. Subjects were randomized to receive pioglitazone 30?mg/d and tretinoin 10?mg/BID for six months or two matching placebos. ALSFRS-R scores were followed monthly. At baseline and at the final visit, lumbar punctures (LPs) were performed to measure cerebrospinal fluid (CSF) biomarker levels. Results. Subjects treated with tretinoin, pioglitazone, and riluzole had an average rate of decline on the ALSFRS-R scale of ?1.02 points per month; subjects treated with placebo and riluzole had a rate of decline of ?.86 (P = .18). Over six months of therapy, CSF tau levels decreased in subjects randomized to active treatment and increased in subjects on placebo. Further higher levels of pNF-H at baseline correlated with a faster rate of progression. Conclusion. ALS patients who were treated with tretinoin and pioglitazone demonstrated no slowing on their disease progression. Interestingly, the rate of disease progression was strongly correlated with levels of pNFH in the CSF at baseline. PMID:22830016

  18. Proteoform analysis of lipocalin-type prostaglandin D-synthase from human cerebrospinal fluid by isoelectric focusing and superficially porous liquid chromatography with Fourier transform mass spectrometry.

    PubMed

    Zhang, Junmei; Corbett, John R; Plymire, Daniel A; Greenberg, Benjamin M; Patrie, Steven M

    2014-05-01

    Lipocalin-type prostaglandin D-synthase (L-PGDS) in cerebrospinal fluid contributes to the maturation and maintenance of the CNS. L-PGDS PTMs may contribute to pathobiology of different CNS diseases, but methods to monitor its proteoforms are limited. Herein, we combined off-gel IEF and superficially porous LC (SPLC) with Fourier transform MS to characterize common cerebrospinal fluid L-PGDS proteoforms. Across 3D physiochemical space (pI, hydrophobicity, and mass), 217 putative proteoforms were observed from 21 to 24 kDa and pI 5-10. Glycoprotein accurate mass information, combined with MS/MS analysis of peptides generated from 2D-fractionated proteoforms, enabled the putative assignment of 208 proteoforms with varied PTM positional occupants. Fifteen structurally related N-glycans at N29 and N56 were observed, with different N-glycan compositional variants being preferred on each amino acid. We also observed that sialic acid content was a major factor for pI shifts between L-PGDS proteoforms. Other putative PTMs characterized include a core-1 HexHexNAc-O-glycan at S7, acetylation at K16 and K138, sulfonation at S41 and T142, and dioxidation at C43 and C145. The IEF-SPLC-MS platform presented provides 30-40× improved peak capacity versus conventional 2DE and shows potential for repeatable proteoform analysis of surrogate PTM-based biomarkers. PMID:24678018

  19. Alterations of the cerebrospinal fluid proteins and subcommissural organ secretion in the arterial hypertension and ventricular dilatation. A study in SHR rats.

    PubMed

    Martínez-Peña y Valenzuela, I; Carmona-Calero, E M; Pérez-González, H; Ormazabal-Ramos, C; Fernández-Rodríguez, P; González-Marrero, I; Castañeyra-Perdomo, A; Ferres-Torres, R

    2006-02-01

    The aim of this work was to analyze the proteins in the cerebrospinal fluid (CSF) of spontaneously hypertensive rats, to study their possible role in the relationship between hydrocephalus, arterial hypertension and alterations in the subcommissural organ. Brains from control Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) sacrificed with chloral hydrate were used. Antiserums against some cerebrospinal fluid protein bands and Reissner's fiber (RF) were used for immunohistochemical study of the SCO. Ventricular dilation was observed in the lateral and third ventricle of the SHR. Third ventricle ependyma showed immunoreactive material (IRM) for antibody against 141 kDa protein band anti-B1 and 117 protein band anti-B2 and the SCO of the SHR showed a decrease of the IRM when compared with WKY rats. An alteration in the expression of anti-RF was found to compare the SCO of the WKY and SHR groups. Our results demonstrate that hydrocephalus and hypertension are interconnected in this kind of rat which produce alterations in SCO secretions and some proteins of the CSF. PMID:16329042

  20. 8-Plex Quantitation of changes in cerebrospinal fluid protein expression in subjects undergoing intravenous immunoglobulin treatment for Alzheimer’s disease

    PubMed Central

    Choe, Leila; D’Ascenzo, Mark; Relkin, Norman R.; Pappin, Darryl; Ross, Phil; Williamson, Brian; Guertin, Steven; Pribil, Patrick; Lee, Kelvin H.

    2013-01-01

    An 8-plex version of an isobaric reagent for the quantitation of proteins using shotgun methods is presented. The 8-plex version of the reagent relies on amine-labeling chemistry of peptides similar to 4-plex reagents. MS/MS reporter ions at 113, 114, 115, 116, 117, 118, 119, and 121 m/z are used to quantify protein expression. This technology which was first applied to a test mixture consisting of 8 proteins and resulted in accurate quantitation, has the potential to increase throughput of analysis for quantitative shotgun proteomics experiments when compared to 2-plex and 4-plex methods. The technology was subsequently applied to a longitudinal study of cerebrospinal fluid proteins from subjects undergoing intravenous immunoglobulin treatment for Alzheimer’s disease. Results from this study identify a number of protein expression changes that occur in cerebrospinal fluid after 3 and 6 months of treatment compared to a baseline and compared to a drug washout period. A visualization tool was developed for this dataset and is presented. The tool can aid in the identification of key peptides and measurements. One conclusion aided by the visualization tool is that there are differences in considering peptide-based observations versus protein-based observations from quantitative shotgun proteomics studies. PMID:17880003

  1. Liquid chromatography-tandem mass spectrometry method for determination of panel of neurotransmitters in cerebrospinal fluid from the rat model for tauopathy.

    PubMed

    Kovac, Andrej; Somikova, Zuzana; Zilka, Norbert; Novak, Michal

    2014-02-01

    Alzheimer's disease (AD) is still being recognized today as an unmet medical need. Currently, there is no cure and early preclinical diagnostic assay available for AD. Therefore much attention is now being directed at the development of novel methods for quantitative determination of AD biomarkers in the cerebrospinal fluid (CSF). Here, we describe the liquid chromatography-tandem mass spectrometry method for determination of 5-hydroxytryptamine (SER), 5-hydroxyindoleacetic acid (5-HIAA), homovanilic acid (HVA), noradrenaline (NADR), adrenaline (ADR), dopamine (DA), glutamic acid (Glu), ?-aminobutyric acid (GABA), 3,4-dihydroxyphenylacetic acid (DOPAC) and histamine (HIS) in cerebrospinal fluid (CSF) from the rat model for human tauopathy. The benzoyl chloride was used as pre-column derivatization reagents. Neurotransmitters and metabolites were analysed on ultra performance liquid chromatography (UPLC) on C18 column in combination with tandem mass spectrometry. The method is simple, highly sensitive and showed excellent linearity with regression coefficients higher than 0.99. The accuracy was in a range of 93-113% for all analytes. The inter-day precision (n=5 days), expressed as %RSD, was in a range 2-10% for all analytes. Using this method we detected significant changes of CSF levels of two important neurotransmitters/metabolites, ADR and 5-HIAA, which correlates with progression of neurodegeneration in our animal model. PMID:24401416

  2. Determination of tranexamic acid (AMCA) and fibrin\\/fibrinogen degradation products in cerebrospinal fluid after aneurysmal subarachnoid haemorrhage

    Microsoft Academic Search

    H. Fodstad; A. Pilbrant; M. Schannon?; S. Strömber?

    1981-01-01

    Summary Six patients with recently ruptured intracranial aneurysms were treated preoperatively with tranexamic acid (AMCA). Two patients received 6 g daily in i.v. infusion, two had 6 g daily by i.v. injection, and two patients were given AMCA 9 g daily by mouth during the first week after bleeding. Serial assays of AMCA and fibrin\\/fibrinogen degradation products (FDP) in cerebrospinal

  3. Cerebrospinal fluid constituents collected at the atlanto-occipital site of xylazine hydrochloride sedated, healthy 8-week-old Holstein calves.

    PubMed Central

    St Jean, G; Yvorchuk-St Jean, K; Anderson, D E; Moore, W E

    1997-01-01

    Cerebrospinal fluid (CSF) collected at the atlanto-occipital site and serum were obtained from 10 male, 8-week-old, Holstein calves after sedation with xylazine hydrochloride. Glucose, creatine kinase, alkaline phosphatase, urea nitrogen, creatinine, sodium, potassium, chloride, calcium, phosphorus, total protein, and albumin were determined in serum and CSF. Optical characteristics, specific gravity, total red blood cell and nucleated cell counts and differentials were also evaluated in the CSF. Additionally, CSF protein electrophoresis and immunoglobulin concentrations were determined. Then, albumin quotients (AQ) were derived. Erythrocytes were observed in 9 of 10 CSF samples. Total nucleated cell counts ranged from 0-10 cells x 10(6)/L with a mean of 3 cells x 10(6)/L. Differential nucleated cell count in the CSF consisted primarily of lymphocytes/small mononuclear cells (57%), fewer monocytes/ large mononuclear cells (38%), and scant neutrophils (4%) and eosinophils (0.05%). The concentration of sodium (134 to 139 mEq/L) was similar to that of serum, but the concentration of potassium (2.8 to 3 mEq/L) was lower than that of serum. Creatine kinase activity (0 to 4 U/L) of CSF was markedly lower than serum activity. The CSF glucose concentration was approximately 80% of the serum value. Cerebrospinal fluid total protein concentration determined by electrophoresis ranged from 110 to 330 mg/L with a mean of 159 mg/L. Cerebrospinal fluid albumin ranged from 48 to 209 mg/L with a mean of 86 mg/L. In all CSF samples, radial immunodiffusion of unaltered CSF and concentrated CSF (four-fold concentration) revealed quantities undetectable by the present techniques in which the lowest standard values for IgG1, IgG, and IgM determinations was 70 mg/L and IgG2 was 30 mg/L. The albumin quotient ranged from 0.15 to 0.65 with a mean of 0.25. Based on the results of this study, CSF may be collected at the atlanto-occipital site safely and efficiently in calves, and reported values for CSF from adult cattle may not be suitable for evaluation of CSF collected from immature cattle. PMID:9114961

  4. Análise molecular de patógenos pela reação em cadeia da polimerase no líquido cefalorraquiano de pacientes infectados com HIV Molecular analysis of pathogens in cerebrospinal fluid by the polymerase chain reaction in HIV-infected patients

    Microsoft Academic Search

    MARISA CHESKY; VIVIAN DE LIMA SPODE; MARIANA JOBIM; PATRICIA HARTSTEIN SALIM; LUIZ SHOZO OZAKI; LUIZ FERNANDO JOBIM

    Introduction: Polymerase chain reaction (PCR) has had great impact on the diagnosis of lymphocytic meningitis and encephalitis over the last decade. It has been extensively used in the diagnosis of central nervous system (CNS) infections for its ability to detect small amounts of target DNA in the cerebrospinal fluid (CSF). Objective: The aim of this study was to identify the

  5. A novel microwave sensor to detect specific biomarkers in human cerebrospinal fluid and their relationship to cellular ischemia during thoracoabdominal aortic aneurysm repair.

    PubMed

    Fok, M; Bashir, M; Fraser, H; Strouther, N; Mason, A

    2015-04-01

    Thoraco-abdominal aneurysms (TAAA) represents a particularly lethal vascular disease that without surgical repair carries a dismal prognosis. However, there is an inherent risk from surgical repair of spinal cord ischaemia that can result in paraplegia. One method of reducing this risk is cerebrospinal fluid (CSF) drainage. We believe that the CSF contains clinically significant biomarkers that can indicate impending spinal cord ischaemia. This work therefore presents a novel measurement method for proteins, namely albumin, as a precursor to further work in this area. The work uses an interdigitated electrode (IDE) sensor and shows that it is capable of detecting various concentrations of albumin (from 0 to 100 g/L) with a high degree of repeatability at 200 MHz (R(2)?=?0.991) and 4 GHz (R(2)?=?0.975). PMID:25686914

  6. Rapid diagnosis of cryptococcal meningitis by use of lateral flow assay on cerebrospinal fluid samples: influence of the high-dose "hook" effect.

    PubMed

    Lourens, Adré; Jarvis, Joseph N; Meintjes, Graeme; Samuel, Catherine M

    2014-12-01

    Cryptococcal meningitis is the most frequent cause of meningitis and a major cause of mortality in HIV-infected adults in Africa. This study evaluated the performance of the lateral flow assay (LFA) on cerebrospinal fluid (CSF) samples for the diagnosis of cryptococcal meningitis against that of existing diagnostic tests. LFA performed on 465 undiluted CSF samples had a sensitivity of 91%. When the LFA was paired with Gram staining, a sensitivity of 100% was achieved after implementation of a dilution step for samples with negative LFA results and the presence of yeasts on microscopy. Microscopy is essential for preventing the reporting of false-negative results due to the high-dose "hook" effect. PMID:25232153

  7. Water influx into cerebrospinal fluid is significantly reduced in senile plaque bearing transgenic mice, supporting beta-amyloid clearance hypothesis of Alzheimer’s disease

    PubMed Central

    Igarashi, Hironaka; Suzuki, Yuji; Kwee, Ingrid L; Nakada, Tsutomu

    2014-01-01

    Recent studies on cerebrospinal fluid (CSF) homeostasis emphasize the importance of water influx into the peri-capillary (Virchow–Robin) space through aquaporin 4 (AQP-4). This water flow is believed to have the functionality equivalent to the systemic lymphatic system and plays a critical role in beta-amyloid clearance. Using a newly developed molecular imaging technique capable of tracing water molecules, in vivo, water influx into the CSF was quantitatively analyzed in senile plaque (SP) bearing transgenic Alzheimer’s disease (AD) model mice. The results unequivocally demonstrated that water influx into CSF is significantly impaired in SP-bearing transgenic mice, the degree of which being virtually identical to that previously observed in AQP-4 knockout mice. The study strongly indicates that disturbance in AQP-4-based water flow and, hence, impairment in beta-amyloid clearance play a significant role in SP formation. PMID:25082552

  8. Rapid and Direct Detection of Herpes Simplex Virus in Cerebrospinal Fluid by Use of a Commercial Real-Time PCR Assay

    PubMed Central

    Espy, Mark J.; Irish, Cole L.

    2014-01-01

    Central nervous system infection due to herpes simplex virus (HSV) is a medical emergency and requires rapid diagnosis and initiation of therapy. In this study, we compared a routine real-time PCR assay for HSV types 1 (HSV-1) and 2 (HSV-2) to a recently FDA-approved direct PCR assay (Simplexa HSV-1/2 Direct; Focus Diagnostics, Cypress, CA) using cerebrospinal fluid samples (n = 100). The Simplexa HSV-1/2 assays demonstrated a combined sensitivity and specificity of 96.2% (50/52) and 97.9% (47/48), respectively. In addition, the Simplexa assay does not require nucleic acid extraction, and the results are available in 60 min. PMID:25274992

  9. Rapid and direct detection of herpes simplex virus in cerebrospinal fluid by use of a commercial real-time PCR assay.

    PubMed

    Binnicker, Matthew J; Espy, Mark J; Irish, Cole L

    2014-12-01

    Central nervous system infection due to herpes simplex virus (HSV) is a medical emergency and requires rapid diagnosis and initiation of therapy. In this study, we compared a routine real-time PCR assay for HSV types 1 (HSV-1) and 2 (HSV-2) to a recently FDA-approved direct PCR assay (Simplexa HSV-1/2 Direct; Focus Diagnostics, Cypress, CA) using cerebrospinal fluid samples (n = 100). The Simplexa HSV-1/2 assays demonstrated a combined sensitivity and specificity of 96.2% (50/52) and 97.9% (47/48), respectively. In addition, the Simplexa assay does not require nucleic acid extraction, and the results are available in 60 min. PMID:25274992

  10. Detection of Toxoplasma gondii soluble antigen, SAG-1(p30), antibody and immune complex in the cerebrospinal fluid of HIV positive or negative individuals.

    PubMed

    Chaves-Borges, F A; Souza, M A; Silva, D A; Kasper, L H; Mineo, J R

    1999-01-01

    Active infection by T. gondii was evaluated by immunoassay for soluble SAG-1 (p30), the major surface antigen from T. gondii, specific antibodies and immune complexes in human cerebrospinal fluid (CSF) samples. A total of 263 samples of CSF were collected from hospitalized patients presenting neurological disorders and analyzed for antibodies to HIV. Patients were divided into two groups: HIV positive (n = 96) or HIV negative (n =167). The results of the assays showed that 45% of all samples were positive for soluble SAG-1. Toxoplasma Ag/Ab immune complexes were detected in 19% of the CSF samples and 62% were positive for T. gondii- specific IgG. A combination of these assays in the presence of clinical findings consistent with active Toxoplasma infection may predict the presence of toxoplasmic encephalitis. Moreover, detection of soluble SAG-1 in the CSF of these individuals appears consistent with active infection. PMID:10671285

  11. Cerebrospinal fluid CXCL13 in clinically isolated syndrome patients: Association with oligoclonal IgM bands and prediction of Multiple Sclerosis diagnosis.

    PubMed

    Ferraro, Diana; Galli, Veronica; Vitetta, Francesca; Simone, Anna Maria; Bedin, Roberta; Del Giovane, Cinzia; Morselli, Franca; Filippini, Maria Maddalena; Nichelli, Paolo Frigio; Sola, Patrizia

    2015-06-15

    Cerebrospinal fluid (CSF) CXCL13 was shown to correlate with markers of intrathecal inflammation and CSF oligoclonal IgM bands (IgMOB) have been associated with a more severe Multiple Sclerosis (MS) course. We correlated CSF CXCL13 levels with clinical, MRI and CSF parameters, including CSF IgMOB, in 110 Clinically Isolated Syndrome (CIS) patients. CSF CXCL13 levels correlated with CSF cell count, total protein, IgG Index and with the presence of CSF IgGOB and IgMOB. CSF CXCL13 levels ?15.4pg/ml showed a good positive predictive value and specificity for a MS diagnosis and for a clinical relapse within one year from onset. PMID:26004159

  12. Correlation between skin, bone, and cerebrospinal fluid layer thickness and optical coefficients measured by multidistance frequency-domain near-infrared spectroscopy in term and preterm infants

    NASA Astrophysics Data System (ADS)

    Demel, Anja; Feilke, Katharina; Wolf, Martin; Poets, Christian F.; Franz, Axel R.

    2014-01-01

    Near-infrared spectroscopy (NIRS) is increasingly used in neonatal intensive care. We investigated the impact of skin, bone, and cerebrospinal fluid (CSF) layer thickness in term and preterm infants on absorption-(?a) and/or reduced scattering coefficients (?s?) measured by multidistance frequency-domain (FD)-NIRS. Transcranial ultrasound was performed to measure the layer thicknesses. Correlations were only statistically significant for ?a at 692 nm with bone thickness and ?s? at 834 nm with skin thickness. There is no evidence that skin, bone, or CSF thickness have an important effect on ?a and ?s?. Layer thicknesses of skin, bone, and CSF in the range studied do not seem to affect cerebral oxygenation measurements by multidistance FD-NIRS significantly.

  13. Bulk derivatization and direct injection of human cerebrospinal fluid for trace-level quantification of endogenous estrogens using trap-and-elute liquid chromatography with tandem mass spectrometry.

    PubMed

    Fan, Hui; Papouskova, Barbora; Lemr, Karel; Wigginton, Jane G; Schug, Kevin A

    2014-08-01

    Although there are existing methods for determining estrogen in human bodily fluids including blood plasma and serum, very little information is available regarding estrogen levels in human cerebrospinal fluid (CSF), which is critical to assess in studies of neuroprotective functions and diffusion of neuroprotective estrogens across the blood-brain barrier. To address this problem, a liquid chromatography with tandem mass spectrometry method for the simultaneous quantification of four endogenous estrogens (estrone, 17?-estradiol, 17?-estradiol, and estriol) in human CSF was developed. An aliquot (300 ?L) of human CSF was bulk derivatized using dansyl chloride in the sample and 10 ?L was directly injected onto a restricted-access media trap column for protein removal. No off-line sample extraction or cleanup was needed. The limits of detection of estrone, 17?-estradiol, 17?-estradiol, and estriol were 17, 28, 13, and 30 pg/mL, respectively, which is in the parts-per-trillion regime. The method was then applied to human CSF collected from ischemic trauma patients. Endogenous estrogens were detected and quantified, demonstrating the effectiveness of this method. PMID:24824590

  14. The distributional nexus of choroid plexus to cerebrospinal fluid, ependyma and brain: toxicologic/pathologic phenomena, periventricular destabilization, and lesion spread.

    PubMed

    Johanson, Conrad; Stopa, Edward; McMillan, Paul; Roth, Daniel; Funk, Juergen; Krinke, Georg

    2011-01-01

    Bordering the ventricular cerebrospinal fluid (CSF) are epithelial cells of choroid plexus (CP), ependyma and circumventricular organs (CVOs) that contain homeostatic transporters for mediating secretion/reabsorption. The distributional pathway ("nexus") of CP-CSF-ependyma-brain furnishes peptides, hormones, and micronutrients to periventricular regions. In disease/toxicity, this nexus becomes a conduit for infectious and xenobiotic agents. The sleeping sickness trypanosome (a protozoan) disrupts CP and downstream CSF-brain. Piperamide is anti-trypanosomic but distorts CP epithelial ultrastructure by engendering hydropic vacuoles; this reflects phospholipidosis and altered lysosomal metabolism. CP swelling by vacuolation may occlude CSF flow. Toxic drug tools delineate injuries to choroidal compartments: cyclophosphamide (vasculature), methylcellulose (interstitium), and piperazine (epithelium). Structurally perturbed CP allows solutes to penetrate the ventricles. There, CSF-borne pathogens and xenobiotics may permeate the ependyma to harm neurogenic stem cell niches. Amoscanate, an anti-helmintic, potently injures rodent ependyma. Ependymal/brain regions near CP are vulnerable to CSF-borne toxicants; this proximity factor links regional barrier breakdown to nearby periventricular pathology. Diverse diseases (e.g., African sleeping sickness, multiple sclerosis) take early root in choroidal, circumventricular, or perivascular loci. Toxicokinetics informs on pathogen, anti-parasitic agent, and auto-antibody distribution along the CSF nexus. CVOs are susceptible to plasma-borne toxicants/pathogens. Countering the physico-chemical and pathogenic insults to the homeostasis-mediating ventricle-bordering cells sustains brain health and fluid balance. PMID:21189316

  15. BEAMing and Droplet Digital PCR Analysis of Mutant IDH1 mRNA in Glioma Patient Serum and Cerebrospinal Fluid Extracellular Vesicles.

    PubMed

    Chen, Walter W; Balaj, Leonora; Liau, Linda M; Samuels, Michael L; Kotsopoulos, Steve K; Maguire, Casey A; Loguidice, Lori; Soto, Horacio; Garrett, Matthew; Zhu, Lin Dan; Sivaraman, Sarada; Chen, Clark; Wong, Eric T; Carter, Bob S; Hochberg, Fred H; Breakefield, Xandra O; Skog, Johan

    2013-01-01

    Development of biofluid-based molecular diagnostic tests for cancer is an important step towards tumor characterization and real-time monitoring in a minimally invasive fashion. Extracellular vesicles (EVs) are released from tumor cells into body fluids and can provide a powerful platform for tumor biomarkers because they carry tumor proteins and nucleic acids. Detecting rare point mutations in the background of wild-type sequences in biofluids such as blood and cerebrospinal fluid (CSF) remains a major challenge. Techniques such as BEAMing (beads, emulsion, amplification, magnetics) PCR and droplet digital PCR (ddPCR) are substantially more sensitive than many other assays for mutant sequence detection. Here, we describe a novel approach that combines biofluid EV RNA and BEAMing RT-PCR (EV-BEAMing), as well droplet digital PCR to interrogate mutations from glioma tumors. EVs from CSF of patients with glioma were shown to contain mutant IDH1 transcripts, and we were able to reliably detect and quantify mutant and wild-type IDH1 RNA transcripts in CSF of patients with gliomas. EV-BEAMing and EV-ddPCR represent a valuable new strategy for cancer diagnostics, which can be applied to a variety of biofluids and neoplasms.Molecular Therapy-Nucleic Acids (2013) 2, e109; doi:10.1038/mtna.2013.28; published online 23 July 2013. PMID:23881452

  16. Absence of recognition of common melanocytic antigens by T cells isolated from the cerebrospinal fluid of a Vogt-Koyanagi-Harada patient

    PubMed Central

    Abad, Sébastien; Colau, Didier; Wildmann, Claude; Delair, Emmanuelle; Dhote, Robin; Brézin, Antoine P.; Kawakami, Yukata; Coulie, Pierre G.; van der Bruggen, Pierre

    2014-01-01

    Purpose Vogt-Koyanagi-Harada (VKH) syndrome is an autoimmune disease characterized by inaugural uveomeningitidis and hearing loss and at late stages a depigmentation in eyes and skin. Melanocytes are the cells common to the four affected tissues, namely eye, brain, inner ear, and skin. Melanocytes are therefore considered as the source of self-antigens. The melanocytic proteins tyrosinase-related protein-1 (TRP1), TRP2, tyrosinase, and gp100 have been proposed as the proteins targeted by autoreactive T cells from VKH patients bearing human leukocyte antigen (HLA)-DRB1*04:05, the HLA allele classically associated with VKH disease. The objective of this work was to determine the antigens recognized by a large number of potentially autoreactive CD4 T lymphocytes obtained from the cerebrospinal fluid of one VKH patient who did not express HLA-DRB1*04:05. Methods T cells were isolated from the cerebrospinal fluid of a newly diagnosed HLA-DRB1*14:01,*15:03;-DPB1*01:01,*04:02 patient in the acute phase of the VKH disease and cloned by limiting dilution. Each of the 107 T cell clones, of which 90% were CD4+, was tested for its ability to secrete cytokines upon contact with autologous antigen-presenting cells loaded with either of the melanocytic proteins TRP1, TRP2, tyrosinase, gp100, Melan-A and KU-MEL-1. The sensitivity of our recombinant bacteria-based approach was validated with a CD4 T cell clone with known antigen specificity. The ability of each of the 107 clones to secrete cytokines upon nonspecific stimulation was verified. Results None of the 107 T cell clones was able to secrete tumor necrosis factor-?, interferon-?, interleukin (IL)-5, or IL-17 upon contact with autologous B cells loaded with any of the six common melanocytic proteins. Nine clones secreted high-level IL-17 upon stimulation with beads coated with antibodies. Conclusions The self-antigens that triggered the VKH disease in this patient probably derive from proteins other than the six melanocytic proteins mentioned above. Further study of antigens that are recognized by potential autoreactive T cells from VKH patients is likely to benefit from testing a broader set of melanocytic proteins. PMID:24991188

  17. Survival Defects of Cryptococcus neoformans Mutants Exposed to Human Cerebrospinal Fluid Result in Attenuated Virulence in an Experimental Model of Meningitis? †

    PubMed Central

    Lee, Anthony; Toffaletti, Dena L.; Tenor, Jennifer; Soderblom, Erik J.; Thompson, J. Will; Moseley, M. Arthur; Price, Michael; Perfect, John R.

    2010-01-01

    Cryptococcus neoformans is a fungal pathogen that encounters various microenvironments during growth in the mammalian host, including intracellular vacuoles, blood, and cerebrospinal fluid (CSF). Because the CSF is isolated by the blood-brain barrier, we hypothesize that CSF presents unique stresses that C. neoformans must overcome to establish an infection. We assayed 1,201 mutants for survival defects in growth media, saline, and human CSF. We assessed CSF-specific mutants for (i) mutant survival in both human bronchoalveolar lavage (BAL) fluid and fetal bovine serum (FBS), (ii) survival in macrophages, and (iii) virulence using both Caenorhabditis elegans and rabbit models of cryptococcosis. Thirteen mutants exhibited significant survival defects unique to CSF. The mutations of three of these mutants were recreated in the clinical serotype A strain H99: deletions of the genes for a cation ATPase transporter (ena1?), a putative NEDD8 ubiquitin-like protein (rub1?), and a phosphatidylinositol 4-kinase (pik1?). Mutant survival rates in yeast media, saline, and BAL fluid were similar to those of the wild type; however, survival in FBS was reduced but not to the levels in CSF. These mutant strains also exhibited decreased intracellular survival in macrophages, various degrees of virulence in nematodes, and severe attenuation of survival in a rabbit meningitis model. We analyzed the CSF by mass spectrometry for candidate compounds responsible for the survival defect. Our findings indicate that the genes required for C. neoformans survival in CSF ex vivo are necessary for survival and infection in this unique host environment. PMID:20696827

  18. Detection of human T-lymphotropic virus type I p40 tax protein in cerebrospinal fluid cells from patients with human T-lymphotropic virus type I-associated myelopathy\\/tropical spastic paraparesis

    Microsoft Academic Search

    Takashi Moritoyo; Shuji Izumo; Hiroyoko Moritoyo; Yuetsu Tanaka; Yoshimasa Kiyomatsu; Masahiro Nagai; Koichiro Usuku; Masaru Sorimachi; Mitsuhiro Osame

    1999-01-01

    We investigated the role of viral transcripts of human T-lymphotropic virus type I (HTLV-I) in the cerebrospinal fluid (CSF) cells and peripheral blood mononuclear cells (PBMCs) of patients with human T-lymphotropic virus type I-associated myelopathy (HAM)\\/tropical spastic paraparesis (TSP). To detect the HTLV-I p40tax protein, we developed a new sensitive method of immunohistochemistry combined with tyramide signal amplification and quantitative

  19. Blood stasis syndrome in Japan and its molecular biological analysis.

    PubMed

    Goto, Hirozo

    2014-07-01

    Blood stasis syndrome is one of the pathological concepts of Oriental traditional medicine. In Oriental traditional medicine, blood is thought of as not only blood but also as a living component of the body. In fact, blood stasis syndrome is related to not just circulation disorders but dermatological and gynecological and other diseases. In Japan, the concept of blood stasis syndrome is based on the past literature, for instance, Synopsis of Golden Chamber (Jin Kui Yao Lue), etc. There are many signs of this syndrome, such as a dry mouth, fullness of the abdomen and rough skin. However, the levels of importance of these signs had been unclear. Therefore, in order to determine the levels of seriousness, a scoring system of blood stasis syndrome was made based on multivariate analysis by Dr. Terasawa (Terasawa's Blood Stasis Score). Using the scoring system, we have studied blood stasis syndrome mainly related to blood circulation using modern techniques of analysis. From the results, we found that patients with blood stasis syndrome showed hemorheological abnormalities, and an improvement in these abnormalities was shown after administration of removing-blood stasis formulae. Furthermore, we have studied blood stasis syndrome from the point of view of molecular biology. We searched for the specific protein expression in blood stasis syndrome by proteomic analysis, and found no specific protein expression. However, there may be a possibility of developing a diagnostic algorithm for blood stasis by construction of a decision tree. During the past few years, as one of the molecular biological factors affecting blood stasis syndrome, we have been studying hypoxia inducible factor, which is located in the upstream of many genes. Above all, blood stasis syndrome is more than just circulatory deficit but encompasses the pathological concept of constant multilateral change in the living body. PMID:24972576

  20. B cells capable of spontaneous IgG secretion in cerebrospinal fluid from patients with multiple sclerosis: dependency on local IL-6 production.

    PubMed

    Perez, L; Alvarez-Cermeño, J C; Rodriguez, C; Roldán, E; Brieva, J A

    1995-09-01

    Cerebrospinal fluid (CSF) from multiple sclerosis (MS) patients contains B cells capable of spontaneous IgG secretion in vitro. This study analyses the function and regulation of these cells. CSF cells obtained from nine MS patients actively produced IgG during 2-3 days in culture, and the activity decreased when CSF cells were cultured in serum-free medium. CSF cells from four controls did not secrete detectable IgG in vitro. Further experiments revealed that IL-6 played a role on MS CSF IgG-secreting cells, as can be deduced from the following findings: (i) the addition of exogenous IL-6, but not of other cytokines, to serum-free cultures restored missing CSF cell IgG secretion (ii) the inclusion of anti-IL-6, but not of control, blocking MoAb reduced IgG secretion by CSF cells in fetal calf serum (FCS)-containing cultures; and (iii) CSF cells were capable of active IL-6 production in the presence of FCS. These results suggest that endogenous IL-6 production by MS CSF cells seems to be responsible for inducing CSF IgG-secreting B cells to reach terminal differentiation. PMID:7664492

  1. B cells capable of spontaneous IgG secretion in cerebrospinal fluid from patients with multiple sclerosis: dependency on local IL-6 production.

    PubMed Central

    Perez, L; Alvarez-Cermeño, J C; Rodriguez, C; Roldán, E; Brieva, J A

    1995-01-01

    Cerebrospinal fluid (CSF) from multiple sclerosis (MS) patients contains B cells capable of spontaneous IgG secretion in vitro. This study analyses the function and regulation of these cells. CSF cells obtained from nine MS patients actively produced IgG during 2-3 days in culture, and the activity decreased when CSF cells were cultured in serum-free medium. CSF cells from four controls did not secrete detectable IgG in vitro. Further experiments revealed that IL-6 played a role on MS CSF IgG-secreting cells, as can be deduced from the following findings: (i) the addition of exogenous IL-6, but not of other cytokines, to serum-free cultures restored missing CSF cell IgG secretion (ii) the inclusion of anti-IL-6, but not of control, blocking MoAb reduced IgG secretion by CSF cells in fetal calf serum (FCS)-containing cultures; and (iii) CSF cells were capable of active IL-6 production in the presence of FCS. These results suggest that endogenous IL-6 production by MS CSF cells seems to be responsible for inducing CSF IgG-secreting B cells to reach terminal differentiation. PMID:7664492

  2. iTRAQ-based quantitative proteomic analysis of cerebrospinal fluid reveals NELL2 as a potential diagnostic biomarker of tuberculous meningitis.

    PubMed

    Yang, Yongtao; Mu, Jun; Chen, Guanghui; Zhan, Yuan; Zhong, Jiaju; Wei, Youdong; Cheng, Ke; Qin, Bin; You, Hongmin; Xie, Peng

    2015-05-01

    Tuberculous meningitis (TBM) is a serious complication of tuberculosis that affects the central nervous system. As TBM may result in permanent sequelae and death, rapid, accurate diagnostic tests using novel biomarkers are required for the early diagnosis and treatment of TBM. A quantitative proteomic study was therefore performed to identify differential proteins in the cerebrospinal fluid (CSF) obtained from TBM patients (n=12) and healthy controls (n=12). CSF samples were labelled with iTRAQ™ and analyzed by LC-MS/MS. Gene ontology and Pathway analysis were conducted using DAVID bioinformatics resources. Neural epidermal growth factor-like like 2 (NELL2) with the largest fold-change value was selected for validation by western blotting. Proteomic phenotyping revealed over-representation in two inflammation-associated processes, complement and coagulation cascades as well as cell adhesion molecules. Western blotting showed a significant decrease in NELL2 levels in TBM subjects compared to healthy controls. The AUC analysis revealed NELL2 was able to distinguish TBM subjects from healthy controls with 83.3% sensitivity and 75% specificity. In conclusion, the results showed that CSF NELL2 is a potential diagnostic biomarker for TBM. Further evaluation of these findings in larger studies including anti-tuberculosis medicated and unmedicated patient cohorts with other intracranial infectious diseases is required for clinical translation. PMID:25760060

  3. Diagnosed tuberculous meningitis using cerebrospinal fluid polymerase chain reaction in patients hospitalized with the diagnosis of meningitis in referral hospitals in Isfahan

    PubMed Central

    Shirani, Kiana; Talaei, Zahra; Yaran, Majid; Ataei, Behrooz; Mehrabi-Koushki, Ali; Khorvash, Farzin

    2015-01-01

    Background: Tuberculosis (TB) remains one of the leading infectious diseases throughout the world. Among various forms of extrapulmonary TB, tuberculous meningitis (TBM) is the most severe form and remains a major global health problem with a high mortality rate. Our study was designed to evaluate tuberculous polymerase chain reaction (PCR) positive rate in patients who present with fairly long symptoms of meningitis. Materials and Methods: The 162 Patients with an indolent onset of symptoms compatible with central nervous system infection were admitted. Sample of cerebrospinal fluid (CSF) was evaluated for biochemistry and tuberculous real-time PCR. Data analyzed by Student's t-test and Fisher's test. Results: Patients were mostly male (69.8%), with a median age of 43.69 ± 22.67 years. CSF real-time PCR results in 6 patients (3.7%) were positive for tuberculous DNA. Of these 6 patients, 4 of whom were men and two of whom were women. In other words, the frequency of positive tuberculous DNA was in male 5.3% and female 1.4%, respectively. Conclusion: Given that we live in Iran and in the vicinity of the tuberculous endemic countries, if we face a meningitis case with lasting symptoms and tendency to be chronic, TBM should be considered.

  4. Increased neuropeptide Y-like immunoreactivity in cerebrospinal fluid and plasma of human immunodeficiency virus-infected patients: relationship to HIV encephalopathy.

    PubMed

    Malessa, R; Heimbach, M; Brockmeyer, N H; Hengge, U; Rascher, W; Michel, M C

    1996-03-01

    Neuropeptide Y (NPY) is one of the most abundant and phylogenetically best conserved peptides in the mammalian central and peripheral nervous system where it plays an important role in the regulation of cardiovascular, metabolic, endocrine, immunological and cognitive functions. In a prospective study we determined neuropeptide Y-like immunoreactivity (NPY-LI) in cerebrospinal fluid (CSF) and plasma of 95 HIV-seropositive (n = 49) or seronegative (n = 46) patients who underwent diagnostic CSF examination. CSF and plasma NPY-LI but not noradrenaline concentrations were higher in seropositive than in seronegative patients indicating that raised levels of NPY-LI did not result from a non-specific activation of the sympathetic nervous system. Increased CSF NPY-LI was positively correlated with the degree of HIV encephalopathy (P < 0.01, Kruskal-Wallis test). Inflammatory disorders of the central nervous system and dementia due to other causes in HIV-seronegative patients were not associated with increased CSF NPY-LI. Our data suggest that increased CSF NPY-LI is a relatively specific phenomenon of HIV encephalopathy and may be involved in the pathogenesis of HIV-related neurological dysfunction. The links between retroviral infection and increased expression of neuropeptide Y and their pathophysiological implications remain to be determined. PMID:8815163

  5. P-glycoprotein contributes to the blood-brain, but not blood-cerebrospinal fluid, barrier in a spontaneous canine p-glycoprotein knockout model.

    PubMed

    Mealey, Katrina L; Greene, Stephen; Bagley, Rodney; Gay, John; Tucker, Russ; Gavin, Patrick; Schmidt, Kari; Nelson, Frederick

    2008-06-01

    P-glycoprotein is considered to be a major factor impeding effective drug therapy for many diseases of the central nervous system (CNS). Thus, efforts are being made to gain a better understanding of P-glycoprotein's role in drug distribution to brain parenchyma and cerebrospinal fluid (CSF). The goal of this study was to validate and introduce a novel P-glycoprotein-deficient (ABCB1-1Delta) canine model for studying P-glycoprotein-mediated effects of drug distribution to brain tissue and CSF. CSF concentrations of drug are often used to correlate efficacy of CNS drug therapy as a surrogate for determining drug concentration in brain tissue. A secondary goal of this study was to investigate the validity of using CSF concentrations of P-glycoprotein substrates to predict brain tissue concentrations. Loperamide, an opioid that is excluded from the brain by P-glycoprotein, was used to confirm a P-glycoprotein-null phenotype in the dog model. ABCB1-1Delta dogs experienced CNS depression following loperamide administration, whereas ABCB1 wild-type dogs experienced no CNS depression. In summary, we have validated a novel P-glycoprotein-deficient canine model and have used the model to investigate transport of the P-glycoprotein substrate (99m)Tc-sestamibi at the blood-brain barrier and blood-CSF barrier. PMID:18332085

  6. Ventricular cerebrospinal fluid lactate is increased in chronic fatigue syndrome compared with generalized anxiety disorder: an in vivo 3.0 T (1)H MRS imaging study.

    PubMed

    Mathew, Sanjay J; Mao, Xiangling; Keegan, Kathryn A; Levine, Susan M; Smith, Eric L P; Heier, Linda A; Otcheretko, Viktor; Coplan, Jeremy D; Shungu, Dikoma C

    2009-04-01

    Chronic fatigue syndrome (CFS) is a controversial diagnosis because of the lack of biomarkers for the illness and its symptom overlap with neuropsychiatric, infectious, and rheumatological disorders. We compared lateral ventricular volumes derived from tissue-segmented T(1)-weighted volumetric MRI data and cerebrospinal fluid (CSF) lactate concentrations measured by proton MRS imaging ((1)H MRSI) in 16 subjects with CFS (modified US Centers for Disease Control and Prevention criteria) with those in 14 patients with generalized anxiety disorder (GAD) and in 15 healthy volunteers, matched group-wise for age, sex, body mass index, handedness, and IQ. Mean lateral ventricular lactate concentrations measured by (1)H MRSI in CFS were increased by 297% compared with those in GAD (P < 0.001) and by 348% compared with those in healthy volunteers (P < 0.001), even after controlling for ventricular volume, which did not differ significantly between the groups. Regression analysis revealed that diagnosis accounted for 43% of the variance in ventricular lactate. CFS is associated with significantly raised concentrations of ventricular lactate, potentially consistent with recent evidence of decreased cortical blood flow, secondary mitochondrial dysfunction, and/or oxidative stress abnormalities in the disorder. PMID:18942064

  7. Cerebrospinal fluid apolipoprotein E and phospholipid transfer protein activity are reduced in multiple sclerosis; relationships with the brain MRI and CSF lipid variables.

    PubMed

    Vuletic, Simona; Kennedy, Hal; Albers, John J; Killestein, Joep; Vrenken, Hugo; Lütjohann, Dieter; Teunissen, Charlotte E

    2014-07-01

    Apolipoprotein E (apoE), phospholipid transfer protein (PLTP) activity, lipids, total tau and beta amyloid 1-42 (A?42) were measured in cerebrospinal fluid (CSF) from controls (n=38) and multiple sclerosis (MS) patients (n=91). ApoE and PLTP activity were significantly reduced in MS compared to non-inflammatory disease controls (NINDC; p<0.05). In NINDC and MS, apoE correlated with PLTP activity (rs=0.399 and 0.591, respectively), A?42 (rs= 0.609 and 0.483, respectively), and total tau (rs=0.748 and 0.380, respectively; all p<0.05). CSF apoE and PLTP significantly contributed to the variance of the normalized brain volume (NBV) and T2 lesion volume in MS (p<0.001 and p<0.05, respectively). ApoE correlated with CSF cholesterol and 24-hydroxycholesterol in all groups; PLTP activity correlated with CSF cholesterol in controls (p<0.05). PMID:24955324

  8. Use of Z310 Cells as an In Vitro Blood-Cerebrospinal Fluid Barrier Model: Tight Junction Proteins and Transport Properties

    PubMed Central

    Shi, Lewis Zhichang; Li, G. Jane; Wang, Shunzhen; Zheng, Wei

    2009-01-01

    Immortalized rat choroidal epithelial Z310 cells have the potential to become an in vitro model for studying transport of materials at blood-cerebrospinal fluid barrier (BCB) (Shi and Zheng, Brain Research 1057:37-48, 2005). This study was designed to demonstrate the presence of tight junction properties in Z310 cells and the functionality of Z310 monolayer in transport of selected model compounds. Western blot analyses revealed the presence of claudin-1, ZO-1, and occludin in Z310 cells. Transmission electron microscopy showed a “tight junction” type of structure in the sub-apical lateral membranes between adjacent Z310 cells. Real-time RT-PCR revealed that Z310 cells expressed representative transporters such as DMT1, MTP1, TfR, p-glycoprotein, ATP7A, ZnT1, ABCC1, Oat3, OCT1 and OB-Ra. Moreover, Z310 cells cultured in a two-chamber Transwell device possessed the ability to transport zidovudine (anionic drug), thyroxine (hormone), thymidine (nucleoside), and leptin (large polypeptide) with kinetic properties similar to those obtained from the in vitro model based on primary culture of choroidal epithelial cells. Taken together, these data indicate that the Z310 BCB model expresses major tight junction proteins and forms a tight barrier in vitro. The model also exhibits the ability to transport substances of various categories across the barrier. PMID:17825520

  9. Chronic exposure to cerebrospinal fluid of multiple system atrophy in neuroblastoma and glioblastoma cells induces cytotoxicity via ER stress and autophagy activation.

    PubMed

    Wang, Xuejing; Ma, Mingming; Teng, Junfang; Zhang, Jiewen; Zhou, Shuang; Zhang, Ying; Wu, Erxi; Ding, Xuebing

    2015-05-30

    Oncogenesis and neurodegeneration share many common pathogenic pathways, involved in endoplastic reticulum (ER) stress, autophagy, DNA repair, and oxidative stress. However, mechanisms of cross-talking between oncogenesis and neurodegeneration are still unknown. Characterized by abnormal accumulation of ?-synuclein (?-syn) aggregates in central nervous system (CNS), multiple system atrophy (MSA) is classified as ?-synucleinopathy. Rapidly emerging evidence suggests that 'prion-like propagation' of ?-syn aggregates in the regional spread of CNS leads to the progression of ?-synucleinopathy. Whether cerebrospinal fluid (CSF) has deteriorating effects on neurogenic tumor cells and is involved in progression of ?-synucleinopathy has not been explored. Here, we first show the cytotoxic effects of MSA-CSF on the neuroblastoma and glioblastoma cells and its underlying mechanism in vitro. Remarkably, MSA-CSF induced cytotoxicity via activating ER stress-associated apoptosis and autophagy in both SH-SY5Y and U251 cells. The result from in vivo systematic neuropathological analysis reveals that abnormally activated ER stress and autophagy were confined to substantia nigra and cerebellum in mouse CNS following MSA-CSF treatment. Specifically, dopamine neurons in substantia nigra and Purkinje cells in cerebellum cortex were degenerated in MSA-CSF-injected mice. Altogether, these findings demonstrate that MSA-CSF exerts cytotoxicities on nervous system neoplasms and accelerates the progression of synucleinopathies. PMID:25965819

  10. Proteomic Characterization of Cerebrospinal Fluid from Ataxia-Telangiectasia (A-T) Patients Using a LC/MS-Based Label-Free Protein Quantification Technology

    PubMed Central

    Dzieciatkowska, Monika; Qi, Guihong; You, Jinsam; Bemis, Kerry G.; Sahm, Heather; Lederman, Howard M.; Crawford, Thomas O.; Gelbert, Lawrence M.; Rothblum-Oviatt, Cynthia; Wang, Mu

    2011-01-01

    Cerebrospinal fluid (CSF) has been used for biomarker discovery of neurodegenerative diseases in humans since biological changes in the brain can be seen in this biofluid. Inactivation of A-T-mutated protein (ATM), a multifunctional protein kinase, is responsible for A-T, yet biochemical studies have not succeeded in conclusively identifying the molecular mechanism(s) underlying the neurodegeneration seen in A-T patients or the proteins that can be used as biomarkers for neurologic assessment of A-T or as potential therapeutic targets. In this study, we applied a high-throughput LC/MS-based label-free protein quantification technology to quantitatively characterize the proteins in CSF samples in order to identify differentially expressed proteins that can serve as potential biomarker candidates for A-T. Among 204 identified CSF proteins with high peptide-identification confidence, thirteen showed significant protein expression changes. Bioinformatic analysis revealed that these 13 proteins are either involved in neurodegenerative disorders or cancer. Future molecular and functional characterization of these proteins would provide more insights into the potential therapeutic targets for the treatment of A-T and the biomarkers that can be used to monitor or predict A-T disease progression. Clinical validation studies are required before any of these proteins can be developed into clinically useful biomarkers. PMID:22084690

  11. Standardized peptidome profiling of human cerebrospinal fluid by magnetic bead separation and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

    PubMed

    Bruegel, Mathias; Planert, Mathis; Baumann, Sven; Focke, Almut; Bergh, Florian Then; Leichtle, Alexander; Ceglarek, Uta; Thiery, Joachim; Fiedler, Georg Martin

    2009-05-01

    Peptidome profiling of human cerebrospinal fluid (CSF) is a promising tool to identify novel disease-associated biomarkers. Our aim was to develop a standardized protocol for reproducible peptidome profiling of CSF using magnetic bead (MB) separation followed by MALDI-TOF MS. Peptidome fractionation and profiling of CSF were performed using MBs with different surface functionalities. We investigated exogenous variables (storage conditions, freeze-thaw-cycles) and endogenous interferences (albumin, immunoglobulin, blood, leukocytes) in pooled CSF samples. We detected approximately 500 signals with an S/N ratio >10 and an overlap frequency of about 40% in non-pathological CSF. Within- and between-day imprecisions in relative signal intensities ranged from 3 to 28% and 7 to 47%, respectively. CSF storage at room temperature for up to 6 h and at 4 degrees C for up to 3 days did not significantly influence the mass spectra. Consecutive freeze-thaw-cycles significantly affected the mass spectra. High albumin and immunoglobulin content altered the CSF preparation using MB-HIC C8 beads. Blood contamination showed no effect on mass spectra up to a hemoglobin concentration of 0.075 micromol/L. The presence of leukocytes up to a cell number of 30 Mpt/L did not affect mass spectra. Our reliable pretreatment protocol allows standardization of preanalytical modalities and thereby enables reproducible peptidome profiling of human CSF using MB separation followed by MALDI-TOF MS. PMID:19111955

  12. 1H NMR Analysis of Cerebrospinal Fluid from Alzheimer’s Disease Patients: An Example of a Possible Misinterpretation Due to Non-Adjustment of pH

    PubMed Central

    Cruz, Thomas; Balayssac, Stéphane; Gilard, Véronique; Martino, Robert; Vincent, Christian; Pariente, Jérémie; Malet-Martino, Myriam

    2014-01-01

    Two publications from the same research group reporting on the detection of new possible biomarkers for the early diagnosis of Alzheimer’s disease (AD), based on the analysis of cerebrospinal fluid samples (CSF) with 1H Nuclear Magnetic Resonance (NMR), are at the origin of the present study. The authors observed significant differences in 1H NMR spectra of CSF from AD patients and healthy controls and, thus, proposed some NMR signals (without attribution) as possible biomarkers. However, this work was carried out in non-standardized pH conditions. Our study aims at warning about a possible misinterpretation that can arise from 1H NMR analyses of CSF samples if pH adjustment is not done before NMR analysis. Indeed, CSF pH increases rapidly after removal and is subject to changes over conservation time. We first identify the NMR signals described by the authors as biomarkers. We then focus on the chemical shift variations of their NMR signals as a function of pH in both standard solutions and CSF samples. Finally, a principal component analysis of 1H NMR data demonstrates that the same CSF samples recorded at pH 8.1 and 10.0 are statistically differentiated. PMID:24958390

  13. Clinical (video) findings and cerebrospinal fluid neurotransmitters in 2 children with severe chronic bilirubin encephalopathy, including a former preterm infant without marked hyperbilirubinemia VIDEO.

    PubMed

    Merhar, Stephanie L; Gilbert, Donald L

    2005-11-01

    Chronic bilirubin encephalopathy, characterized clinically by extrapyramidal movement abnormalities, vertical gaze abnormalities, and hearing loss, results from neuronal injury after marked hyperbilirubinemia in term and preterm infants. In premature infants, bilirubin staining of specific brain structures has been described at autopsy after only moderate hyperbilirubinemia, but classic chronic bilirubin encephalopathy without marked hyperbilirubinemia has been reported only rarely. We report a case of a 7-year-old, former 29-weeks' gestation, gravely ill premature infant with a peak bilirubin level of 13.3 mg/dL in the neonatal period. We compare this case with a 12-year-old, former term infant with a peak bilirubin level of 49.4 mg/dL on day 10 of life. Both children have dystonia, athetosis, upward gaze palsy, and sensorineural hearing loss, with MRIs showing characteristic abnormal signal in the globus pallidus. We add previously unreported cerebrospinal fluid neurotransmitter levels that show a mild decrease in the dopamine metabolite homovanillic acid in the former premature infant only. PMID:16264013

  14. Few Patient, Treatment, and Diagnostic or Microbiological Factors, Except Complications and Intermittent Negative Cerebrospinal Fluid (CSF) Cultures During First CSF Shunt Infection, Are Associated With Reinfection

    PubMed Central

    Simon, Tamara D.; Mayer-Hamblett, Nicole; Whitlock, Kathryn B.; Langley, Marcie; Kestle, John R. W.; Riva-Cambrin, Jay; Rosenfeld, Margaret; Thorell, Emily A.

    2014-01-01

    Background The relationship between first and subsequent cerebrospinal fluid (CSF) shunt infections is poorly understood. By understanding the factors associated with increased risk of reinfection, researchers may provide optimal treatment strategies at the time of first infection. The objective of this study was to describe and compare children with and without CSF shunt reinfection. Methods A retrospective cohort study was performed among 118 children who underwent initial CSF shunt placement and developed first CSF shunt infection. The primary outcome variable was CSF shunt reinfection. Patient risk factors and medical and surgical management of initial CSF shunt placement and first CSF shunt infection were compared between children with and without reinfection. Results Of 118 children with first infection, 31 (26%) developed a reinfection during the study period (overall median follow-up, 2096 days). Factors associated with reinfection in this cohort included ventriculoatrial or complex shunt at initial CSF shunt placement, complications after first CSF shunt infection, and intermittent negative CSF cultures. Conclusions Few patient or treatment factors were associated with reinfection. Factors associated with difficult-to-treat first CSF shunt infection, including complications after first CSF shunt infection and intermittent negative CSF cultures, were associated with reinfection. Clinicians who treat patients with unusual CSF shunts or more difficult first infections should have a high index of suspicion for reinfection after treatment is completed. PMID:24567841

  15. Cerebral toxoplasmosis after umbilical cord blood transplantation diagnosed by the detection of anti-toxoplasma specific IgM antibody in cerebrospinal fluid.

    PubMed

    Inaba, Akiko; Koh, Hideo; Nakashima, Yasuhiro; Nishimoto, Mitsutaka; Hayashi, Yoshiki; Okamura, Hiroshi; Inoue, Atsushi; Nanno, Satoru; Nakane, Takahiko; Shimono, Taro; Nakamae, Hirohisa; Hino, Masayuki

    2014-04-01

    Cerebral toxoplasmosis is a rare, potentially fatal, complication of hematopoietic cell transplantation. Early definitive diagnosis is very difficult and it may be associated with a poor prognosis. Herein, we describe a 60-year-old woman who developed cerebral toxoplasmosis after cord blood transplantation for myelodysplastic syndrome. During treatment with tacrolimus and methylprednisolone for relapsed grade 2 acute gut GVHD, fever and disturbance of consciousness occurred on day 210. Brain MRI showed multiple ring-enhancing nodular lesions in the thalamus, basal ganglia, brainstem, and subcortical