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1

CEREBROSPINAL FLUID STASIS AND ITS CLINICAL SIGNIFICANCE  

PubMed Central

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

Whedon, James M.; Glassey, Donald

2010-01-01

2

The Maze of the Cerebrospinal Fluid Discovery  

PubMed Central

The author analyzes a historical, long, and tortuous way to discover the cerebrospinal fluid. At least 35 physicians and anatomists described in the text have laid the fundamentals of recognition of this biological fluid's presence. On the basis of crucial anatomical, experimental, and clinical works there are four greatest physicians who should be considered as equal cerebrospinal fluid's discoverers: Egyptian Imhotep, Venetian Nicolo Massa, Italian Domenico Felice Cotugno, and French François Magendie. PMID:24396600

2013-01-01

3

Tick borne encephalitis without cerebrospinal fluid pleocytosis.  

PubMed

BackgroundTick borne encephalitis is the most frequent vector-transmitted infectious disease of the central nervous system in Europe and Asia. The disease caused by European subtype of tick borne encephalitis virus has typically a biphasic clinical course with the second phase presenting as meningitis, meningoencephalitis, or meningoencephalomyelitis. Cerebrospinal fluid pleocytosis is considered a condition sine qua non for the diagnosis of neurologic involvement in tick borne encephalitis, which in routine clinical practice is confirmed by demonstration of serum IgM and IgG antibodies to tick borne encephalitis virus.Case presentationHere we present a patient from Slovenia, an area highly endemic for tick borne encephalitis, with encephalitis but without cerebrospinal fluid pleocytosis in whom tick borne encephalitis virus infection of the central nervous system was demonstrated.ConclusionCerebrospinal fluid pleocytosis is not mandatory in encephalitis caused by tick borne encephalitis virus. In daily clinical practice, in patients with neurologic symptoms/signs compatible with tick borne encephalitis and the risk of exposure to ticks in a tick borne encephalitis endemic region, the search for central nervous system infection with tick borne encephalitis virus is warranted despite the lack of cerebrospinal fluid pleocytosis. PMID:25403498

Stupica, Da A; Strle, Franc; Av I-Upanc, Tatjana; Logar, Mateja; Pe Avar, Bla; Bajrovi, Fajko F

2014-11-18

4

Contemporary management of cerebrospinal fluid rhinorrhea  

Microsoft Academic Search

Management of patients with cerebrospinal fluid rhinorrhea (CSF) remains controversial. Most studies recommend either an endoscopic or an external extracranial approach, depending on the surgeon’s preference. Eighteen patients with CSF rhinorrhea have been managed at our institution since 1990. The causes of the CSF rhinorrhea consisted of functional endoscopic sinus surgery (7), lateral rhinotomy with excision of a benign nasal

MARK K. WAX; HASSAN H. RAMADAN; ORLANDO ORTIZ; STEPHEN J. WETMORE

1997-01-01

5

Acrylamide exposure impairs blood-cerebrospinal fluid barrier function  

PubMed Central

Previous studies show that chronic acrylamide exposure leads to central and peripheral neu-ropathy. However, the underlying mechanisms remained unclear. In this study, we examined the permeability of the blood-cerebrospinal fluid barrier, and its ability to secrete transthyretin and transport leptin of rats exposed to acrylamide for 7, 14, 21 or 28 days. Transthyretin levels in cerebrospinal fluid began to decline on day 7 after acrylamide exposure. The sodium fluorescein level in cerebrospinal fluid was increased on day 14 after exposure. Evans blue concentration in cerebrospinal fluid was increased and the cerebrospinal fluid/serum leptin ratio was decreased on days 21 and 28 after exposure. In comparison, the cerebrospinal fluid/serum albumin ratio was increased on day 28 after exposure. Our findings show that acrylamide exposure damages the blood-cerebrospinal fluid barrier and impairs secretory and transport functions. These changes may underlie acrylamide-induced neurotoxicity. PMID:25206854

Yao, Xue; Yan, Licheng; Yao, Lin; Guan, Weijun; Zeng, Fanxu; Cao, Fuyuan; Zhang, Yanshu

2014-01-01

6

Cerebrospinal Fluid Biomarker Candidates for Parkinsonian Disorders  

PubMed Central

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

Constantinescu, Radu; Mondello, Stefania

2013-01-01

7

A new look at cerebrospinal fluid circulation  

PubMed Central

According to the traditional understanding of cerebrospinal fluid (CSF) physiology, the majority of CSF is produced by the choroid plexus, circulates through the ventricles, the cisterns, and the subarachnoid space to be absorbed into the blood by the arachnoid villi. This review surveys key developments leading to the traditional concept. Challenging this concept are novel insights utilizing molecular and cellular biology as well as neuroimaging, which indicate that CSF physiology may be much more complex than previously believed. The CSF circulation comprises not only a directed flow of CSF, but in addition a pulsatile to and fro movement throughout the entire brain with local fluid exchange between blood, interstitial fluid, and CSF. Astrocytes, aquaporins, and other membrane transporters are key elements in brain water and CSF homeostasis. A continuous bidirectional fluid exchange at the blood brain barrier produces flow rates, which exceed the choroidal CSF production rate by far. The CSF circulation around blood vessels penetrating from the subarachnoid space into the Virchow Robin spaces provides both a drainage pathway for the clearance of waste molecules from the brain and a site for the interaction of the systemic immune system with that of the brain. Important physiological functions, for example the regeneration of the brain during sleep, may depend on CSF circulation. PMID:24817998

2014-01-01

8

Imhotep and the Discovery of Cerebrospinal Fluid  

PubMed Central

Herbowski (2013) suggested recently the Egyptian Imhotep from the 3rd dynasty in Egypt to be the discoverer of cerebrospinal fluid. There are, however, no sources within the first 2000 years after Imhotep suggesting him to be in any way connected with the field of medicine. Over the course of three millennia Imhotep evolves into the sage who besides architecture also masters the arts of medicine, magic, astronomy, and astrology, at the same time as him being transformed from man to demi-God, and finally to a God. The identification of Imhotep as a doctor has thus little to do with facts and it is unlikely that he had anything to do with the Edwin-Smith papyrus from a much later period where CSF is first mentioned. PMID:24744920

Blomstedt, Patric

2014-01-01

9

Imhotep and the discovery of cerebrospinal fluid.  

PubMed

Herbowski (2013) suggested recently the Egyptian Imhotep from the 3rd dynasty in Egypt to be the discoverer of cerebrospinal fluid. There are, however, no sources within the first 2000 years after Imhotep suggesting him to be in any way connected with the field of medicine. Over the course of three millennia Imhotep evolves into the sage who besides architecture also masters the arts of medicine, magic, astronomy, and astrology, at the same time as him being transformed from man to demi-God, and finally to a God. The identification of Imhotep as a doctor has thus little to do with facts and it is unlikely that he had anything to do with the Edwin-Smith papyrus from a much later period where CSF is first mentioned. PMID:24744920

Blomstedt, Patric

2014-01-01

10

Characterization of individual mouse cerebrospinal fluid proteomes  

SciTech Connect

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.

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

2014-03-20

11

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

PubMed

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

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

2013-09-17

12

Familial calcification of the basal ganglia with cerebrospinal fluid pleocytosis.  

PubMed Central

Two related infants with microcephaly, spastic quadriplegia, and profound retardation are reported. Both showed extensive bilateral symmetrical calcification of the basal ganglia with cerebrospinal fluid pleocytosis. Images PMID:3712392

Mehta, L; Trounce, J Q; Moore, J R; Young, I D

1986-01-01

13

Choroid epithelial cells: source cerebrospinal fluid progesterone in sheep?  

Microsoft Academic Search

Karahan S., Yarim G. F., Yarim M. Choroid epithelial cells: the source of cerebrospinal fluid progesterone in sheep? Summary The present study was conducted to immunolocalize 3b-hydroxysteroid dehydrogenase (3b-HSD), an enzyme metabolizing pregnenolone to progesterone in the choroid plexus of the lateral ventricle in sheep, as well as to measure progesterone concentration in cerebrospinal fluid (CSF) and plasma using radioimmunoassay

SIYAMI KARAHAN; GUL FATMA YARIM; MURAT YARIM

2007-01-01

14

Doxepin concentrations in plasma and cerebrospinal fluid.  

PubMed

Doxepin--like other antidepressant drugs (ADs)--shows a variable antidepressant effect in clinical practice. The cause for this variability is as yet unclear; however, pharmacokinetic factors such as the variable permeability of doxepin into the cerebrospinal fluid (CSF), may contribute to the difference in therapeutic efficacy. We measured and correlated the concentration of doxepin and its active metabolite nordoxepin in both the plasma and CSF. Plasma and CSF samples were taken simultaneously from 21 patients who were treated with doxepin due to different clinical indications. The plasma concentration of both doxepin and nordoxepin correlated significantly with the oral dosage of doxepin (doxepin: r = +0.66, p < 0.001; nordoxepin: r = +0.78, p < 0.0001; Spearman's correlation). Furthermore, we found significant correlations between the plasma and CSF concentrations of both doxepin (r = +0.71; p < 0.001; Pearson's correlation) and nordoxepin (r = +0.74; p < 0.001). These highly significant correlations between the plasma and CSF concentrations indicate a constant CSF permeability of doxepin and its active metabolite nordoxepin. PMID:21350940

Schomburg, Robert; Remane, Daniela; Fassbender, Klaus; Maurer, Hans H; Spiegel, Jörg

2011-04-01

15

Cerebrospinal Fluid Space Alterations in Melancholic Depression  

PubMed Central

Melancholic depression is a biologically homogeneous clinical entity in which structural brain alterations have been described. Interestingly, reports of structural alterations in melancholia include volume increases in Cerebro-Spinal Fluid (CSF) spaces. However, there are no previous reports of CSF volume alterations using automated whole-brain voxel-wise approaches, as tissue classification algorithms have been traditionally regarded as less reliable for CSF segmentation. Here we aimed to assess CSF volumetric alterations in melancholic depression and their clinical correlates by means of a novel segmentation algorithm (‘new segment’, as implemented in the software Statistical Parametric Mapping-SPM8), incorporating specific features that may improve CSF segmentation. A three-dimensional Magnetic Resonance Image (MRI) was obtained from seventy patients with melancholic depression and forty healthy control subjects. Although imaging data were pre-processed with the ‘new segment’ algorithm, in order to obtain a comparison with previous segmentation approaches, tissue segmentation was also performed with the ‘unified segmentation’ approach. Melancholic patients showed a CSF volume increase in the region of the left Sylvian fissure, and a CSF volume decrease in the subarachnoid spaces surrounding medial and lateral parietal cortices. Furthermore, CSF increases in the left Sylvian fissure were negatively correlated with the reduction percentage of depressive symptoms at discharge. None of these results were replicated with the ‘unified segmentation’ approach. By contrast, between-group differences in the left Sylvian fissure were replicated with a non-automated quantification of the CSF content of this region. Left Sylvian fissure alterations reported here are in agreement with previous findings from non-automated CSF assessments, and also with other reports of gray and white matter insular alterations in depressive samples using automated approaches. The reliable characterization of CSF alterations may help in the comprehensive characterization of brain structural abnormalities in psychiatric samples and in the development of etiopathogenic hypotheses relating to the disorders. PMID:22761673

Via, Esther; Cardoner, Narcís; Pujol, Jesús; Martínez-Zalacaín, Ignacio; Hernández-Ribas, Rosa; Urretavizacaya, Mikel; López-Solà, Marina; Deus, Joan; Menchón, José Manuel; Soriano-Mas, Carles

2012-01-01

16

Cerebrospinal fluid somatostatin, mood, and cognition in multiple sclerosis  

Microsoft Academic Search

Background: Cerebrospinal fluid (CSF) somatostatin (SS) levels have been shown to be decreased in multiple sclerosis (MS) during relapse as well as in disorders characterized by depression or cognitive impairment. Since MS is often associated with depression and cognitive impairment, we examined both the effect of course of illness on CSF SS as well as the variance in SS attributable

Catherine A Roca; Tung-Ping Su; Sarah Elpern; Henry McFarland; David R Rubinow

1999-01-01

17

Cerebrospinal fluid volume analysis for hydrocephalus diagnosis and clinical research  

E-print Network

with various types of hydrocephalus in [3, 4], whereas it is limited to normal pressure hydrocephalus, iCerebrospinal fluid volume analysis for hydrocephalus diagnosis and clinical research Alain Lebreta in range [0.63, 4.61] for hydrocephalus patients. This indicates that a robust distinction between

Paris-Sud XI, Université de

18

Cerebrospinal fluid hepatocyte growth factor level in meningitis  

Microsoft Academic Search

Background and Purpose: Hepatocyte growth factor (HGF) is a multifunctional cytokine that has been found to be elevated in tuberculous and bacterial meningitis, but no evaluation has been undertaken of its usefulness in identifying various forms of aseptic meningitis. Methods: In a retrospective study, the levels of HGF in the cerebrospinal fluid of 65 patients were measured prior to treatment.

Cheng-Len Sy; Hung-Chin Tsai; Shue-Ren Wann; Susan Shin-Jung Lee; Yung-Ching Liu; Yao-Shen Chen

2008-01-01

19

Abnormalities of cerebrospinal fluid amino-acids in purulent meningitis  

PubMed Central

Serial measurements were made of the cerebrospinal fluid and plasma amino-acid concentrations in 12 patients with purulent meningitis. Marked increases in the concentrations of most CSF amino-acids were found, possibly caused by altered transport mechanisms in the inflamed meninges and choroid plexuses. PMID:512663

Corston, R. N.; McGale, E. H. F.; Stonier, C.; Hutchinson, E. C.; Aber, G. M.

1979-01-01

20

A new look at cerebrospinal fluid movement.  

PubMed

Brinker et al. extensively reviewed recent findings about CSF circulation in a recent article: "A new look at cerebrospinal circulation", but did not analyze some important available data in sufficient detail. For example, our findings as well as some clinical data and experimental results obtained from different animal species, do not support unidirectional CSF circulation but strongly suggest that there are cardiac cycle-dependent systolic-diastolic to-and-fro cranio-spinal CSF movements. These are based on: a) physiological oscillations of arterial and venous blood during cranio-spinal blood circulation; b) respiratory activity, and c) body activity and posture. That kind of complex CSF movement could explain the observed distribution of many different substances in all directions along the CSF system and within central nervous system tissue. It seems that efflux transport systems at capillary endothelium may be more important for brain homeostasis than the removal of metabolites by CSF flow. Thus, when discussing the CSF dynamics we suggest that a more appropriate term would be CSF movement rather than CSF circulation. PMID:25089184

Oreškovi?, Darko; Klarica, Marijan

2014-01-01

21

A new look at cerebrospinal fluid movement  

PubMed Central

Brinker et al. extensively reviewed recent findings about CSF circulation in a recent article: “A new look at cerebrospinal circulation”, but did not analyze some important available data in sufficient detail. For example, our findings as well as some clinical data and experimental results obtained from different animal species, do not support unidirectional CSF circulation but strongly suggest that there are cardiac cycle-dependent systolic-diastolic to-and-fro cranio-spinal CSF movements. These are based on: a) physiological oscillations of arterial and venous blood during cranio-spinal blood circulation; b) respiratory activity, and c) body activity and posture. That kind of complex CSF movement could explain the observed distribution of many different substances in all directions along the CSF system and within central nervous system tissue. It seems that efflux transport systems at capillary endothelium may be more important for brain homeostasis than the removal of metabolites by CSF flow. Thus, when discussing the CSF dynamics we suggest that a more appropriate term would be CSF movement rather than CSF circulation. PMID:25089184

2014-01-01

22

Upcoming candidate cerebrospinal fluid biomarkers of Alzheimer’s disease  

PubMed Central

Dementia due to Alzheimer’s disease (AD) is estimated to reach epidemic proportions by the year 2030. Given the limited accuracy of current AD clinical diagnosis, biomarkers of AD pathologies are currently being sought. Reductions in cerebrospinal fluid levels of ?-amyloid 42 (a marker of amyloid plaques) and elevations in tau species (markers of neurofibrillary tangles and/or neurodegeneration) are well-established as biomarkers useful for AD diagnosis and prognosis. However, novel markers for other features of AD pathophysiology (e.g., ?-amyloid processing, neuroinflammation and neuronal stress/dysfunction) and for other non-AD dementias are required to improve the accuracy of AD disease diagnosis, prognosis, staging and therapeutic monitoring (theragnosis). This article discusses the potential of several promising novel cerebrospinal fluid analytes, highlights the next steps critical for advancement in the field, and provides a prediction on how the field may evolve in 5–10 years. PMID:22917147

Fagan, Anne M; Perrin, Richard J

2012-01-01

23

Cerebrospinal fluid S-100 protein levels in neurological pathologies  

Microsoft Academic Search

The aim of this paper was to evaluate S-100 concentration in cerebrospinal fluid (CSF) from patients with different neurological\\u000a disorders, and in subjects with no proven neurological pathology, in order to study possible differences in their protein\\u000a concentrations. The total number of patient-samples examined was 119 (58 males and 61 females; mean age 35 yrs, 1–79 yrs).\\u000a Based on the

J. R. Infante; A. Martínez; J. Ochoa; F. Cañadillas; M. Torres-Avisbal; J. A. Vallejo; F. M. González; C. Pacheco; J. M. Latre

2003-01-01

24

Neurogenesis at the Brain–Cerebrospinal Fluid Interface  

PubMed Central

Cerebral cortical progenitor cells can be classified into several different types, and each progenitor type integrates cell-intrinsic and cell-extrinsic cues to regulate neurogenesis. On one hand, cell-intrinsic mechanisms that depend upon appropriate apical-basal polarity are established by adherens junctions and apical complex proteins and are particularly important in progenitors with apical processes contacting the lateral ventricle. The apical protein complexes themselves are con-centrated at the ventricular surface, and apical complex proteins regulate mitotic spindle orientation and cell fate. On the other hand, remarkably little is known about how cell-extrinsic cues signal to progenitors and couple with cell-intrinsic mechanisms to instruct neurogenesis. Recent research shows that the cerebrospinal fluid, which contacts apical progenitors at the ventricular surface and bathes the apical complex of these cells, provides growth- and survival-promoting cues for neural progenitor cells in developing and adult brain. This review addresses how the apical-basal polarity of progenitor cells regulates cell fate and allows progenitors to sample diffusible signals distributed by the cere-brospinal fluid. We also review several classes of signaling factors that the cerebrospinal fluid distributes to the developing brain to instruct neurogenesis. PMID:21801012

Lehtinen, Maria K.; Walsh, Christopher A.

2013-01-01

25

Idiopathic normal-pressure hydrocephalus, cerebrospinal fluid biomarkers, and the cerebrospinal fluid tap test.  

PubMed

Cerebrospinal fluid (CSF) biomarkers, including soluble amyloid ?-42 (A?-42) and phosphorylated-tau (P-tau), reflect core pathophysiological features of Alzheimer's disease (AD). AD is frequently a concomitant pathology in older patients with idiopathic normal-pressure hydrocephalus (iNPH), and somewhat similar altered CSF dynamics exist in both AD and iNPH. We therefore investigated relationships between lumbar CSF biomarkers A?-42 and P-tau and clinical parameters in iNPH patients, along with differences in these biomarkers between CSF tap test (CSFTT) responders and non-responders. Thirty-one iNPH patients (14 CSFTT responders and 17 CSFTT non-responders) were included in the final analysis. We found lower CSF A?-42 correlated with poor cognitive performance (r=0.687, p<0.001 for Korean Mini Mental State Examination; r=0.568, p=0.001 for Frontal Assessment Battery; r=-0.439, p=0.014 for iNPH grading scale [iNPHGS] cognitive score; r=-0.588, p=0.001 for Clinical Dementia Rating Scale), and lower CSF P-tau correlated with gait dysfunction (r=-0.624, p<0.001 for Timed Up and Go Test; r=-0.652, p<0.001 for 10meter walking test; r=-0.578, p=0.001 for Gait Status Scale; r=-0.543, p=0.002 for iNPHGS gait score). In subgroup analysis, CSF P-tau/A?-42 ratios were significantly higher in CSFTT non-responders compared to responders (p=0.027). Two conjectures are suggested. One, CSF biomarkers may play different and characteristic roles in relation to different iNPH symptoms such as cognition and gait. Two, comorbid AD pathology in iNPH patients may affect the response to the CSFTT. Larger studies using combinations of other biomarkers associated with AD would be necessary to evaluate these hypotheses. PMID:24836892

Kang, Kyunghun; Ko, Pan-Woo; Jin, Myungwon; Suk, Kyoungho; Lee, Ho-Won

2014-08-01

26

Aspergillus Galactomannan Antigen in the Cerebrospinal Fluid of Bone Marrow Transplant Recipients with Probable Cerebral Aspergillosis  

PubMed Central

The Aspergillus galactomannan test was performed on cerebrospinal fluid and serum samples from 5 patients with probable cerebral aspergillosis and from 16 control patients. Cerebrospinal fluid galactomannan levels were significantly higher in aspergillosis patients, and most galactomannan was produced intrathecally. Comparison of serum galactomannan values in pulmonary and cerebral aspergillosis patients showed significant overlapping. Detection of Aspergillus galactomannan in cerebrospinal fluid may be diagnostic of cerebral aspergillosis. PMID:11923380

Viscoli, Claudio; Machetti, Marco; Gazzola, Paola; De Maria, Andrea; Paola, Dimitri; Van Lint, Maria Teresa; Gualandi, Francesca; Truini, Mauro; Bacigalupo, Andrea

2002-01-01

27

Hydroxyapatite cement resistant to fragmentation following full cerebrospinal fluid bathing.  

PubMed

Prolonged cerebrospinal fluid bathing of cranioplasty cement frequently results in breakdown of the cement implants. A 5-year-old boy with a history of severe head trauma at 2 weeks of age presented with marked protrusion of the entire superior temporal bone and inferior parietal bone. The defect was elevated by more than 1 cm and was associated with a 4.5 x 3-cm skull defect located above and behind the right ear. There also was pulsatile tissue at the depths of the defect. A computed tomographic scan taken of the head revealed an expanding skull fracture from a dural defect with underlying brain herniation. The cranial lesion was repaired with OsteoVation hydroxyapatite cement. Within 8 weeks, the fluid encased the cranioplasty site. This resolved following implantation of a shunting device. At 2 and 12 months after the repair, the implant was still palpably solid without breakdown and did not fragment despite the prolonged bathing in cerebrospinal fluid. PMID:18216703

Muhonen, Michael G; Lonyai, Anna; Westhout, Franklin D

2008-01-01

28

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

Microsoft Academic Search

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

D. Oreskovic; M. Klarica; M. Vukic

2001-01-01

29

Cerebrospinal fluid leak presenting as oculorrhea after blunt orbitocranial trauma.  

PubMed

Cerebrospinal fluid (CSF) leak is an uncommon but well-documented occurrence after blunt head trauma, typically manifesting as otorrhea or rhinorrhea. Blunt cranio-orbital trauma also may cause CSF leak into the orbit, manifesting as orbitocele, blepharocele, chemosis, or tearing ("oculorrhea"). We report a patient who developed oculorrhea after blunt head trauma, and neuroimaging disclosed comminuted fractures of the left frontal, greater sphenoid wing, nasal, and maxillary bones. Because he also displayed chemosis and markedly reduced ocular ductions and periocular pain, carotid-cavernous fistula was suspected but appropriate vascular imaging was negative. Aspiration of subconjunctival fluid was positive for beta-2 transferrin, a specific marker for CSF. Chemosis lessened and the oculorrhea ceased spontaneously within 6 days of the trauma. This manifestation of CSF leak must not be overlooked because of the threat of meningitis. PMID:24621864

Apkarian, Alexandra O; Hervey-Jumper, Shawn L; Trobe, Jonathan D

2014-09-01

30

The function and structure of the cerebrospinal fluid outflow system  

PubMed Central

This review traces the development of our understanding of the anatomy and physiological properties of the two systems responsible for the drainage of cerebrospinal fluid (CSF) into the systemic circulation. The roles of the cranial and spinal arachnoid villi (AV) and the lymphatic outflow systems are evaluated as to the dominance of one over the other in various species and degree of animal maturation. The functional capabilities of the total CSF drainage system are presented, with evidence that the duality of the system is supported by the changes in fluid outflow dynamics in human and sub-human primates in hydrocephalus. The review also reconciles the relative importance and alterations of each of the outflow systems in a variety of clinical pathological conditions. PMID:20565964

2010-01-01

31

The presence of trace amines in postmortem cerebrospinal fluid in humans.  

PubMed

The postmortem levels of biogenic amines in cerebrospinal fluid may represent a useful tool in defining some pathological conditions; no information is available concerning the occurrence of trace amines in postmortem cerebrospinal fluid. Thus, the occurrence of octopamine, synephrine and tyramine were evaluated by using a HPLC system in 20 postmortem samples of cerebrospinal fluid (obtained from 11 males and 9 females) and their levels were compared with those of 20 living subjects (obtained from 11 males and 9 females). The results show that trace amines dramatically increase in the postmortem cerebrospinal fluid (100, 20, and 4 fold increase for tyramine, octopamine, and synephrine respectively). To our knowledge, our data represent the first time trace amines have been identified in postmortem cerebrospinal fluid and the dramatic increase observed for tyramine has the potential of becoming a new tool in forensic science for better defining the time of death. PMID:15932098

Balbi, Tiziana; Fusco, Mariella; Vasapollo, Domenico; Boschetto, Roberta; Cocco, Patrizia; Leon, Alberta; Farruggio, Angelo

2005-05-01

32

Evaluation of Microbial Bacterial and Fungal Diversity in Cerebrospinal Fluid Shunt Infection  

PubMed Central

Background Cerebrospinal fluid shunt infection can be recalcitrant. Recurrence is common despite appropriate therapy for the pathogens identified by culture. Improved diagnostic and therapeutic approaches are required, and culture-independent molecular approaches to cerebrospinal fluid shunt infections have not been described. Objectives To identify the bacteria and fungi present in cerebrospinal fluid from children with cerebrospinal fluid shunt infection using a high-throughput sequencing approach, and to compare those results to those from negative controls and conventional culture. Methods This descriptive study included eight children ?18 years old undergoing treatment for culture-identified cerebrospinal fluid shunt infection. After routine aerobic culture of each cerebrospinal fluid sample, deoxyribonucleic acid (DNA) extraction was followed by amplification of the bacterial 16S rRNA gene and the fungal ITS DNA region tag-encoded FLX-Titanium amplicon pyrosequencing and microbial phylogenetic analysis. Results The microbiota analyses for the initial cerebrospinal fluid samples from all eight infections identified a variety of bacteria and fungi, many of which did not grow in conventional culture. Detection by conventional culture did not predict the relative abundance of an organism by pyrosequencing, but in all cases, at least one bacterial taxon was detected by both conventional culture and pyrosequencing. Individual bacterial species fluctuated in relative abundance but remained above the limits of detection during infection treatment. Conclusions Numerous bacterial and fungal organisms were detected in these cerebrospinal fluid shunt infections, even during and after treatment, indicating diverse and recalcitrant shunt microbiota. In evaluating cerebrospinal fluid shunt infection, fungal and anaerobic bacterial cultures should be considered in addition to aerobic bacterial cultures, and culture-independent approaches offer a promising alternative diagnostic approach. More effective treatment of cerebrospinal fluid shunt infections is needed to reduce unacceptably high rates of reinfection, and this work suggests that one effective strategy may be reduction of the diverse microbiota present in infection. PMID:24421877

Simon, Tamara D.; Pope, Christopher E.; Browd, Samuel R.; Ojemann, Jeffrey G.; Riva-Cambrin, Jay; Mayer-Hamblett, Nicole; Rosenfeld, Margaret; Zerr, Danielle M.; Hoffman, Lucas

2014-01-01

33

Remote Cerebral and Cerebellar Hemorrhage after Massive Cerebrospinal Fluid Leakage  

PubMed Central

Dural tears can occur during spinal surgery and may lead to cerebrospinal fluid (CSF) leakage which is rarely involved in remote cerebellar hemorrhage. Only a few of cases of simultaneous cerebral and cerebellar hemorrhage have been reported in the English literature. We experienced a case of multiple remote cerebral and cerebellar hemorrhages in a 63-year-old man who exhibited no significant neurologic deficits after spinal surgery. Magnetic resonance imaging (MRI) performed 4 days after the surgery showed a large amount of CSF leakage in the lumbosacral space. The patient underwent the second surgery for primary repair of the dural defect, but complained of headache after dural repair surgery. Brain MRI taken 6 days after the dural repair surgery revealed multifocal remote intracerebral and cerebellar hemorrhages in the right temporal lobe and both cerebellar hemispheres. We recommend diagnostic imaging to secure early identification and treatment of this complication in order to prevent serious neurologic deficits. PMID:22737308

You, Sung-Hye; Lee, Nam Joon; Suh, Jung-Keun

2012-01-01

34

Peptidome Analysis of Cerebrospinal Fluid by LC-MALDI MS  

PubMed Central

We report on the analysis of endogenous peptides in cerebrospinal fluid (CSF) by mass spectrometry. A method was developed for preparation of peptide extracts from CSF. Analysis of the extracts by offline LC-MALDI MS resulted in the detection of 3,000–4,000 peptide-like features. Out of these, 730 peptides were identified by MS/MS. The majority of these peptides have not been previously reported in CSF. The identified peptides were found to originate from 104 proteins, of which several have been reported to be involved in different disorders of the central nervous system. These results support the notion that CSF peptidomics may be viable complement to proteomics in the search of biomarkers of CNS disorders. PMID:22880031

Hölttä, Mikko; Zetterberg, Henrik; Mirgorodskaya, Ekaterina; Mattsson, Niklas; Blennow, Kaj; Gobom, Johan

2012-01-01

35

Agitation in Dementia: Relation to Core Cerebrospinal Fluid Biomarker Levels  

PubMed Central

Background The objective of this study was to examine the associations of agitation with the cerebrospinal fluid dementia biomarkers total-tau (T-tau), phosphorylated-tau (P-tau) and A?1-42. Methods One hundred patients (mean age ± SD, 78.6 ± 7.5 years) with dementia and neuropsychiatric symptoms, of whom 67% were female, were included. Agitation was measured using the Cohen-Mansfield Agitation Inventory (CMAI; 46.5 ± 11.8 points). Results Total CMAI correlated with T-tau [rs (31) = 0.36, p = 0.04] and P-tau [rs (31) = 0.35, p = 0.05] in patients with Alzheimer's disease (AD; n = 33) but not in the total dementia population (n = 95). Conclusions Our results suggest that tau-mediated pathology including neurofibrillary tangles and the intensity of the disease process might be associated with agitation in AD. PMID:25298777

Bloniecki, Victor; Aarsland, Dag; Cummings, Jeffrey; Blennow, Kaj; Freund-Levi, Yvonne

2014-01-01

36

Stability of herpes simplex virus DNA in cerebrospinal fluid specimens.  

PubMed

Polymerase chain reaction methods are becoming the standard for the diagnosis of herpes simplex virus (HSV) encephalitis. Little is known, however, about the stability of HSV DNA in cerebrospinal fluid (CSF) specimens. Our results demonstrate that HSV DNA is extremely stable in CSF specimens containing lymphocytes and monocytes. We observed little DNA degradation in specimens stored for 30 days at room temperature (20-23 degrees C), refrigerator temperature (2-8 degrees C), or freezer temperatures (-18 to -22 degrees C and -69 to -72 degrees C). Specimen storage conditions are therefore not so critical for HSV encephalitis detection as for other viral illnesses. It is therefore not necessary to perform a second lumbar puncture to obtain a fresh specimen for the detection of HSV DNA. PMID:8955615

Wiedbrauk, D L; Cunningham, W

1996-12-01

37

Orbital cerebrospinal fluid accumulation after complicated pterional-orbitozygomatic craniotomy.  

PubMed

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

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

2014-12-01

38

Stability of monoamine metabolites in human cerebrospinal fluid.  

PubMed

Concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were measured in human lumbar cerebrospinal fluid following storage at room temperature and 4 degrees C for intervals up to 72 hours. These monoamine metabolites were quantitated using a high-performance liquid chromatographic-electrochemical detector technique. No significant difference could be detected in any of the three metabolites stored at room temperature for up to 48 hours. Addition of ascorbic acid to CSF had no measurable effect on the levels of HVA and 5-HIAA. Repeated thawing and freezing produced no detectable change in metabolite levels. The results indicate that these monoamine metabolites are stable at room temperature for up to 48 hours after lumbar puncture and that the addition of an antioxidant, such as ascorbic acid, is not necessary. The data also demonstrate that immediate refrigeration or freezing of samples is not required for maintenance of metabolite levels. PMID:6180677

Langlais, P J; Bird, E D; McEntee, W J

1982-07-01

39

The cerebrospinal fluid: regulator of neurogenesis, behavior, and beyond  

PubMed Central

The cerebrospinal fluid (CSF) has attracted renewed interest as an active signaling milieu that regulates brain development, homeostasis, and disease. Advances in proteomics research have enabled an improved characterization of the CSF from development through adulthood, and key neurogenic signaling pathways that are transmitted via the CSF are now being elucidated. Due to its immediate contact with neural stem cells in the developing and adult brain, the CSF's ability to swiftly distribute signals across vast distances in central nervous system is opening avenues to novel and exciting therapeutic approaches. In this review, we will discuss the development of the choroid plexus-CSF system, and review the current literature on how the CSF actively regulates mammalian brain development, behavior, and responses to traumatic brain injury. PMID:22415326

Zappaterra, Mauro W.; Lehtinen, Maria K.

2013-01-01

40

Proteomic analysis of cerebrospinal fluid extracellular vesicles: a comprehensive dataset.  

PubMed

Extracellular vesicles (EVs) are present in human cerebrospinal fluid (CSF), yet little is known about their protein composition. The aim of this study is to provide a comprehensive analysis of the proteome of CSF EVs by electron microscopy and high resolution tandem mass spectrometry (MS/MS) in conjunction with bioinformatics. We report an extensive catalog of 1315 proteins identified in EVs isolated from two different CSF pools by ultracentrifugation, including 230 novel EV proteins. Out of 1315 proteins, 760 were identified in both CSF pools and about 30% of those were also quantitatively enriched in the EV fraction versus the soluble CSF fraction. The proteome of CSF EVs was enriched in exosomal markers such as alix and syntenin-1, heat shock proteins and tetraspanins and contained a high proportion of brain-derived proteins (n=373). Interestingly, several known biomarkers for neurodegenerative diseases such as the amyloid precursor protein, the prion protein and DJ-1 were identified in the EV fractions. Our dataset represents the first comprehensive inventory of the EV proteome in CSF, underscoring the biomarker potential of this organelle. Further comparative studies on CSF EVs isolated from patients diagnosed with neurological disorders are warranted. Data are available via ProteomeXchange with identifier PXD000608. Biological significance In this study we analyzed the protein composition of extracellular vesicles isolated from pooled samples of human cerebrospinal fluid (CSF). CSF is a colorless fluid surrounding the brain and the spinal cord, important for the physiology of the central nervous system, ensuing mechanical protection, regulation of brain blood flow and elimination of byproducts of the brain. Since brain (patho)physiology is reflected in CSF, this biological fluid represents an ideal source of soluble and vesicle-based biomarkers for neurological diseases. Here we confirm the presence of exosome-like extracellular vesicles in CSF, underscoring a potential role in the physiology of the brain. These extracellular vesicles provide a rich source of candidate biomarkers, representing a brain "fluid biopsy". Most interestingly, the involvement of extracellular vesicles in transferring toxic proteins such as ?-synuclein and ?-amyloid has been postulated as one of the mechanisms involved in the spreading of neurodegeneration to different brain areas. In line with this, we show that human CSF extracellular vesicles contain prionogenic proteins such as the amyloid precursor protein and the prion protein. Delineating the protein composition of extracellular vesicles in CSF is a first and crucial step to comprehend their origin and their function in the central nervous system and to establish their biomarker potential. PMID:24769233

Chiasserini, Davide; van Weering, Jan R T; Piersma, Sander R; Pham, Thang V; Malekzadeh, Arjan; Teunissen, Charlotte E; de Wit, Heidi; Jiménez, Connie R

2014-06-25

41

Neonatal Meningitis: What Is the Correlation Among Cerebrospinal Fluid Cultures, Blood Cultures, and Cerebrospinal Fluid Parameters?  

Microsoft Academic Search

BACKGROUND.Meningitis is a substantial cause of morbidity and mortality in neo- nates. Clinicians frequently use the presence of positive blood cultures to deter- mine whether neonates should undergo lumbar puncture. Abnormal cerebrospi- nal fluid (CSF) parameters are often used to predict neonatal meningitis and determine length and type of antibiotic therapy in neonates with a positive blood culture and negative

Harmony P. Garges; M. Anthony Moody; C. Michael Cotten; P. Brian Smith; Kenneth F. Tiffany; Robert Lenfestey; Jennifer S. Li; Vance G. Fowler

2010-01-01

42

Cysticercus Antigens in Cerebrospinal Fluid Samples from Patients with Neurocysticercosis  

PubMed Central

Antigens were detected in cerebrospinal fluid (CSF) samples from patients with neurocysticercosis (NC) by enzyme-linked immunosorbent assay (ELISA) using polyclonal sera of rabbit anti-Taenia solium cysticerci (anti-Tso) and anti- Taenia crassiceps cysticerci vesicular fluid (anti-Tcra or anti-Tcra <30 kDa). A group of NC patients (n = 174) were studied (NC), including 40 patients in different phases of the disease. ELISAs carried out with the anti-Tso, anti-Tcra, and anti-Tcra <30 kDa showed sensitivities of 81.2, 90, and 95.8% and specificities of 82, 98, and 100%, respectively. The 14- and 18-kDa low-molecular-weight peptides were only detected in CSF samples from patients with NC by immunoblotting with anti-Tso and anti-Tcra sera. Because of the importance of the diagnosis and prognosis of cysticercosis, the detection of antigens may contribute as an additional marker to the study and clarification of the parasite-host relationship. PMID:11526181

Pardini, Alessandra Xavier; Vaz, Adelaide José; Machado, Luis Dos Ramos; Livramento, José Antônio

2001-01-01

43

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

NASA Astrophysics Data System (ADS)

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.

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

1982-05-01

44

Marked increase of matrix metalloproteinase 9 in cerebrospinal fluid of patients with fungal or tuberculous meningoencephalitis  

Microsoft Academic Search

Matrix metalloproteinases (MMPs) are believed to play an essential role in the breakdown of the extracellular matrix macromolecules in the blood–cerebrospinal fluid barrier and blood–brain barrier (BBB). In this study, the levels of MMP-2 and MMP-9 and their common tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) were measured in the cerebrospinal fluid (CSF) from patients with various meningitides including aseptic,

Eiji Matsuura; Fujio Umehara; Teruto Hashiguchi; Noboru Fujimoto; Yasunori Okada; Mitsuhiro Osame

2000-01-01

45

Diagnosis of neurosyphilis by examination of the cerebrospinal fluid.  

PubMed Central

Thirty-six patients with reactive results in the cerebrospinal fluid to the Treponema pallidum haemagglutination assay (CSF-TPHA) were investigated by further serological tests for confirmation of active neurosyphilis. The results of the TPHA and fluorescent treponemal antibody tests were reactive in all CSF samples from patients with acute untreated neurosyphilis and from most patients with late latent syphilis but no signs of involvement of the central nervous system. The demonstration of 19S-IgM antibodies against Treponema pallidum in the CSF was a better indication of activity of the disease than the Venereal Disease Research Laboratory test. Ten of 11 patients with untreated acute neurosyphilis had reactive results in the solid-phase haemadsorption test for CSF-IgM (CSF-IgM-SPHA test). The TPHA index, which relates the CSF-TPHA titre to the albumin quotient and thus excludes errors from disturbed function of the blood-brain barrier, was above 100 in all but one of the patients with acute neurosyphilis but below 100 after treatment. Patients with late latent syphilis and without CNS signs had TPHA indices below 5. Thus a nonreactive CSF-TPHA test result excludes neurosyphilis but reactive CSF-IgM-SPHA results and TPHA indices above 100 strongly indicative active disease. PMID:7023601

Luger, A; Schmidt, B L; Steyrer, K; Schonwald, E

1981-01-01

46

Subtotal petrosectomy and cerebrospinal fluid leakage in unilateral anacusis.  

PubMed

Objective?This study presents a group of patients experiencing recurrent cerebrospinal fluid (CSF) leakage associated with ipsilateral anacusis who underwent subtotal petrosectomies with the goal of stopping the CSF leak and preventing meningitis. Materials and Methods?Eight patients with CSF leakage were enrolled: three patients with giant vestibular schwannomas had CSF leakage after gamma knife failure and subsequent removal via a retrosigmoid approach; two patients had malformations at the level of the inner ear with consequent translabyrinthine fistulas; two had posttraumatic CSF leakages; and one had a CSF leakage coexisting with an encephalocele. Two patients developed meningitis that resolved with antibiotic therapy. Each patient had preoperative anacusis and vestibular nerve areflexia on the affected side. Results?The patients with congenital or posttraumatic CSF leaks had undergone at least one unsuccessful endaural approach to treat the fistula. All eight patients were treated successfully with a subtotal petrosectomy. The symptoms disappeared within 2 months postoperatively. No meningitis, signs of fistula, or other symptoms occurred during the follow-up. Conclusion?A subtotal petrosectomy should be the first choice of treatment in patients with recurrent CSF leakage whenever there is associated unilateral anacusis. PMID:25452896

Magliulo, Giuseppe; Iannella, Giannicola; Ciniglio Appiani, Mario; Re, Massimo

2014-12-01

47

Lateral sphenoid sinus recess cerebrospinal fluid leak: a case series.  

PubMed

The lateral recess of the sphenoid sinus is one of the most common sites of meningocele and spontaneous cerebrospinal fluid (CSF) leak. Despite the availability of several techniques for closure of skull base defects occurring in this location, recurrence still poses a major challenge. This report reviews the experience of surgical repair of lateral sphenoid sinus recess CSF leak at a tertiary referral center and provides a brief discussion of this rare lesion. Nine surgeries were performed for six cases of spontaneous lateral sphenoid sinus recess CSF leak (two revisions and one repair of a new defect). Two patients presented with intracranial hypertension (ICH) and four with meningocele or meningoencephalocele. The transpterygoid approach was used in two procedures. A multilayer graft was used in seven cases and a nasoseptal flap in two. Three patients received lumbar or ventricular shunts, and one received acetazolamide for ICH management. Two minor complications were recorded, and the overall surgical success rate was 78 %. We conclude that nasoseptal flaps are a valid option for repair of recurrent CSF leaks, particularly in the lateral sphenoid sinus recess. Furthermore, identification and correction of ICH plays an essential role in the success of treatment in this patient population. PMID:24748381

Melo, Nelson Almeida d'Ávila; Borges, Bruno Barros Pinto; Magliarelli Filho, Pedro Augusto; Godoy, Maria Dantas Costa Lima; Pereira, Larissa Vilela; Pinna, Fabio de Rezende; Voegels, Richard Louis

2014-09-01

48

A cerebrospinal fluid glucose biosensor for diabetes mellitus.  

PubMed

A cerebrospinal fluid (CSF) glucose biosensor is introduced. The biosensor is a polarimeter that measures the rotation of plane polarized light proportional to glucose concentration. Preliminary in vitro studies revealed a linear response with good sensitivity over a range of glucose solutions (0-400 mg/dl). Anesthetized, adult dogs underwent intravenous glucose loading, and these preliminary in vivo studies resulted in good correlation (r = 0.98) between CSF polarimeter readings and CSF glucose by laboratory assay. This in vivo correlation suggests that both mutarotation of glucose anomer and changes from other optically active substances present in CSF are either negligible or constant over the range of glucose concentrations studied. The CSF polarimeter showed a significant rise soon after the intravenous loading of glucose (1-30 min) but a longer lag time (45-60 min) between the peak blood glucose and peak CSF polarimeter reading. This preliminary work extends, to the CSF, the concept of measuring optical rotation. PMID:1421610

Gilbert, J W; Weiser, H C; Holladay, F P

1992-01-01

49

Reduced cerebrospinal fluid ethanolamine concentration in major depressive disorder  

PubMed Central

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

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

50

Monoamines in the brain cerebrospinal fluid of facial pain patients.  

PubMed Central

The purpose of the study was to assay monoamines in cerebrospinal fluid (CSF) obtained from the trigeminal cistern of 64 patients with intractable facial pain. The CSF was analyzed for homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), end-product markers of activity for the dopamine, serotonin, and norepinephrine systems, respectively. HVA averaged 121 ng/mL in these facial pain patients, compared to 150 to 550 ng/mL in 10 studies of ventricular brain CSF in assorted psychiatric and pain patients. 5-HIAA averaged 29 to ng/mL in our facial pain patients compared to 60 to 120 ng/mL in nine studies of ventricular brain CSF in assorted psychiatric and neurological patients. Trigeminal cistern CSF MHPG averaged 9 ng/mL, similar to the range of 13 studies of lumbar CSF of assorted psychiatric and pain diagnoses. These results indicate that (1) the electrochemical detection method provides a unique way of accurately measuring nanogram concentrations of multiple monoamines in a little as 0.25 mL of CSF; (2) trigeminal cistern and posterior fossa brain CSF monoamine metabolites reflect a different profile of dopaminergic and serotonergic functioning in these facial pain patients from that previously reported with lumbar CSF measurements of other patients; and (3) trigeminal sensory ganglion or brain dopamine and serotonin systems may be concomitantly dysfunctional in intractable facial pain. PMID:7504420

Bouckoms, A. J.; Sweet, W. H.; Poletti, C.; Lavori, P.; Carr, D.; Matson, W.; Gamache, P.; Aronin, N.

1992-01-01

51

Two-compartment model of radioimmunotherapy delivered through cerebrospinal fluid  

PubMed Central

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

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

2011-01-01

52

Cerebrospinal fluid apolipoprotein E levels in subacute sclerosing panencephalitis.  

PubMed

Neurofibrillary tangles (NFTs) have been shown in 20% of subacute sclerosing panencephalitis (SSPE) cases. NFTs contain paired helical filaments formed by hyperphosphorylated tau. The intraneuronal tau metabolism and the rate of formation of paired helical filaments can be regulated by interactions between tau and isoforms of Apolipoprotein E (Apo E). Tau binds in vitro to Apo E3, interferes with the hyperphosphorylation of tau and may reduce the formation of NFTs. We investigated cerebrospinal fluid (CSF) Apo E levels in SSPE (n=37) and age-matched control (n=38) groups. The median level of total Apo E and Apo E4 were lower in the SSPE than the control group (p<0.001 and p=0.002). On the other hand, median Apo E3 level (0.28±0.23 ?g/ml) was higher in the SSPE group (p<0.001). Such elevated levels of ApoE3 might play a role in controlling the formation of NFTs in SSPE. Because NFT-associated neurodegeneration is a slow process, comparison of the long-term clinical course of SSPE cases with high and low Apo E3 levels might provide further understanding or the role of these molecules in this disease, and help the planning of neuroprotective treatment. PMID:21788110

Yüksel, Deniz; Ichiyama, Takashi; Yilmaz, Deniz; Anlar, Banu

2012-04-01

53

Cerebrospinal fluid amino acids in pathological gamblers and healthy controls.  

PubMed

Amino acids, such as valine, isoleucine and leucine compete with tyrosine and tryptophan for transport into the brain and might thus affect the central serotonin and catecholamine patterns. Furthermore, the excitatory amino acids glutamic acid, aspartic acid and glycine are known to act on the N-methyl-D-aspartate receptor, which is part of the reward system. Based on these facts, we have explored the role of cerebrospinal fluid (CSF) amino acids in pathological gambling. Concentrations of amino acids were determined in CSF obtained from one female and 11 pathological male gamblers and 11 healthy male controls. In an ANCOVA with best subset regression, pathological male gamblers had higher CSF levels of the excitatory glutamic and aspartic acids, as well as of phenylalanine, isoleucine, citrulline and glycine. A negative contribution of glycine in interaction with the neuraxis distance might mirror a reduced spinal supply or an altered elimination of glycine in pathological gamblers. A decreasing CSF gradient from the first (0-6 ml) to the third (13-18 ml) CSF fraction was found for glutamic acid, glycine, leucine, isoleucine, lysine, ornithine and glutamine in both pathological gamblers and healthy controls. A decreasing gradient was found, however, for aspartic acid and phenylalanine in pathological male gamblers. The altered pattern of CSF amino acids in pathological gamblers might exert an influence on central monoamines as well as on N-methyl-D-aspartate receptor function. PMID:18259089

Nordin, Conny; Gupta, Ramesh C; Sjödin, Ingemar

2007-01-01

54

Cerebrospinal Fluid Apolipoprotein E Concentration and Progression of Alzheimer's Disease.  

PubMed

Background/Objective: Apolipoprotein E plays a role in the pathogenesis of Alzheimer's disease (AD). Cerebrospinal fluid (CSF) and plasma level alterations have been reported in AD patients. In search of a potential biomarker, which would be predictive of cognitive, functional, or motor decline, we analyzed CSF apolipoprotein E (ApoE) levels of AD patients in this regard. Methods: Subjects with newly diagnosed AD enrolled into an observational study were followed up longitudinally. Neuropsychological testing and physical examination were performed annually. In a sub-cohort of patients, where baseline CSF ApoE concentration values were available, multiple regression analyses were used to determine possible associations of CSF ApoE concentration and speed of decline on different cognitive, functional, and motor scales (MMSE, iADL, bADL, GDS, UPDRSIII) adjusting for possible confounders. Results: No association of CSF ApoE levels and speed of decline on the various scales could be established (p = 0.09 to 0.88). Nevertheless, the use of neuroleptic drugs could be linked to higher velocity of global and extrapyramidal deterioration (p = 0.04 and 0.05 for GDS and UPDRSIII, respectively), but not to other outcomes (MMSE, bADL, and iADL). Conclusion: Herein, CSF ApoE at time of AD diagnosis could not be shown to be a viable biomarker for future cognitive, functional, or motor decline. Expectedly, the use of neuroleptic drugs was associated with detrimental effects. PMID:25125466

Schmidt, Christian; Gerlach, Nicole; Peter, Christoph; Gherib, Kerim; Lange, Katharina; Fride, Tim; Zerr, Inga

2014-08-13

55

Reduced cerebrospinal fluid ethanolamine concentration in major depressive disorder.  

PubMed

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

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

56

Cerebrospinal fluid physiology: visualization of cerebrospinal fluid dynamics using the magnetic resonance imaging Time-Spatial Inversion Pulse method  

PubMed Central

Previously there have been no methods for directly tracing the flow of cerebrospinal fluid (CSF) under physiological conditions, and the circulation of CSF has therefore been studied and visualized by injecting a radioactively labeled tracer or contrast medium visible in x-ray images. The newly developed Time-Spatial Inversion Pulse (Time-SLIP) method makes it possible to directly visualize the flow of CSF using magnetic resonance imaging (MRI), permitting CSF dynamics to be depicted in a certain time frame. The CSF dynamics visualized using Time-SLIP has been found to differ markedly from the classical CSF circulation theory described in medical textbooks. It can be said that research on CSF dynamics has advanced to the next stage with the use of this innovative imaging method. Obtaining a more accurate understanding of normal CSF physiology and pathophysiology should lead to improved diagnostic accuracy, permit the identification of new etiological factors in a variety of diseases, and promote the development of new therapeutic approaches. PMID:25165048

Yamada, Shinya

2014-01-01

57

Cerebrospinal fluid flow abnormalities in patients with neoplastic meningitis. An evaluation using /sup 111/In-DTPA ventriculography  

SciTech Connect

Cerebrospinal fluid flow dynamics were evaluated by /sup 111/In-diethylenetriamine pentaacetic acid (/sup 111/In-DTPA) ventriculography in 27 patients with neoplastic meningitis. Nineteen patients (70 percent) had evidence of cerebrospinal fluid flow disturbances. These occurred as ventricular outlet obstructions, abnormalities of flow in the spinal canal, or flow distrubances over the cortical convexities. Tumor histology, physical examination, cerebrospinal fluid analysis, myelograms, and computerized axial tomographic scans were not sufficient to predict cerebrospinal fluid flow patterns. These data indicate that cerebrospinal fluid flow abnormalities are common in patients with neoplastic meningitis and that /sup 111/In-DTPA cerebrospinal fluid flow imaging is useful in characterizing these abnormalities. This technique provides insight into the distribution of intraventricularly administered chemotherapy and may provide explanations for treatment failure and drug-induced neurotoxicity in patients with neoplastic meningitis.

Grossman, S.A.; Trump, D.L.; Chen, D.C.; Thompson, G.; Camargo, E.E.

1982-11-01

58

Cerebrospinal fluid biomarkers of central catecholamine deficiency in Parkinson’s disease and other synucleinopathies  

PubMed Central

Central catecholamine deficiency characterizes ?-synucleinopathies such as Parkinson’s disease. We hypothesized that cerebrospinal fluid levels of neuronal metabolites of catecholamines provide neurochemical biomarkers of these disorders. To test this hypothesis we measured cerebrospinal fluid levels of catechols including dopamine, norepinephrine and their main respective neuronal metabolites dihydroxyphenylacetic acid and dihydroxyphenylglycol in Parkinson’s disease and two other synucleinopathies, multiple system atrophy and pure autonomic failure. Cerebrospinal fluid catechols were assayed in 146 subjects—108 synucleinopathy patients (34 Parkinson’s disease, 54 multiple system atrophy, 20 pure autonomic failure) and 38 controls. In 14 patients cerebrospinal fluid was obtained before or within 2 years after the onset of parkinsonism. The Parkinson’s disease, multiple system atrophy and pure autonomic failure groups all had lower cerebrospinal fluid dihydroxyphenylacetic acid [0.86?±?0.09 (SEM), 1.00?±?0.09, 1.32?±?0.12?nmol/l] than controls (2.15?±?0.18?nmol/l; P?cerebrospinal fluid neurochemical evidence for central dopamine and norepinephrine deficiency. Parkinson’s disease and pure autonomic failure involve differential dopaminergic versus noradrenergic lesions. Cerebrospinal fluid dihydroxyphenylacetic acid seems to provide a sensitive means to identify even early Parkinson’s disease. PMID:22451506

Holmes, Courtney; Sharabi, Yehonatan

2012-01-01

59

Cerebrospinal fluid biomarker candidates associated with human WNV neuroinvasive disease.  

PubMed

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

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

2014-01-01

60

Cerebrospinal Fluid Biomarker Candidates Associated with Human WNV Neuroinvasive Disease  

PubMed Central

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

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

2014-01-01

61

Endostatin Level in Cerebrospinal Fluid of Patients with Alzheimer's Disease.  

PubMed

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

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

2014-11-18

62

Cerebrospinal Fluid miRNA Profile in HIV-Encephalitis†  

PubMed Central

MicroRNAs are short non-coding RNAs that modulate gene expression by translational repression. Because of their high stability in intracellular as well as extracellular environments, miRNAs have recently emerged as important biomarkers in several human diseases. However, they have not been tested in the cerebrospinal fluid (CSF) of HIV-1 positive individuals. Here, we present results of a study aimed at determining the feasibility of detecting miRNAs in the CSF of HIV-infected individuals with and without encephalitis (HIVE). We also evaluated similarities and differences between CSF and brain tissue miRNAs in the same clinical setting. We utilized a high throughput approach of miRNA detection arrays and identified differentially expressed miRNAs in the frontal cortex of three cases each of HIV+, HIVE, and HIV? controls, and CSF of ten HIV-positive and ten HIV-negative individuals. For the CSF samples, the group of HIV+ individuals contained nine cases of HIV-Associated Neurological Disorders (HAND) and, among those, four had HIVE. All the HIV-negative samples had non-viral acute disseminate encephalomyelitis. A total of 66 miRNAs were found differentially regulated in HIV+ compared to HIV? groups. The greatest difference in miRNA expression was observed when four cases of HIVE were compared to five non-HIVE cases, previously normalized with the HIV-negative group. After statistical analyses, eleven miRNAs were fund significantly up-regulated in HIVE. Although more clinical samples should be examined, this work represents the first report of CSF miRNAs in HIV-infection and offers the basis for future investigation. PMID:23042033

Pacifici, Marco; Delbue, Serena; Ferrante, Pasquale; Jeansonne, Duane; Kadri, Ferdous; Nelson, Steve; Velasco-Gonzalez, Cruz; Zabaleta, Jovanny; Peruzzi, Francesca

2012-01-01

63

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

PubMed Central

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

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

2010-01-01

64

Mannan-binding lectin in cerebrospinal fluid: a leptomeningeal protein  

PubMed Central

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

2012-01-01

65

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

PubMed

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

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

2008-01-01

66

Cerebrospinal fluid lipoperoxides quantified by liquid chromatography, and determination of reference values.  

PubMed

Cerebrospinal fluid lipoperoxides, measured as the malondialdehyde-thiobarbituric acid (MDA-TBA) adduct, were quantified by adapting the plasma liquid-chromatographic method of Wong et al. (Clin Chem 1987;33:214-20) to cerebrospinal fluid. Reference values for spinal fluid specimens from 91 adults, ages 17 to 95 y, and 37 children, ages 8 d to 8 y, were determined. Their concentrations were not significantly different (P = 0.222), adults having a mean (and SD) of 0.11 (0.06) mumol and children 0.10 (0.04) mumol of MDA per liter. Their ranges were 0.02-0.26 and 0.04-0.21 mumol of MDA per liter, respectively. We found concentrations in cerebrospinal fluid to be increased in several central nervous system disorders, including seizures, cerebral infarction, alcoholic encephalopathy, and, perhaps, prematurity. The presence of other thiobarbituric acid-reactive substances in cerebrospinal fluid stresses the importance of using highly specific techniques when lipoperoxides are measured in body fluids. PMID:2297906

Knight, J A; McClellan, L; Staheli, J K

1990-01-01

67

A comparison of tau protein in cerebrospinal fluid between corticobasal degeneration and progressive supranuclear palsy  

Microsoft Academic Search

Many clinical and pathological discussions have been focused on the difficulty of differential diagnosis between corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) in recent years. This study was conducted to evaluate the usefulness of tau proteins in cerebrospinal fluid (CSF) for the differentiation of these two diseases. Subjects consisted of 10 patients with CBD (four males and six females

Katsuya Urakami; Masatada Mori; Kenji Wada; Hisanori Kowa; Takao Takeshima; Hiroyuki Arai; Hidetada Sasaki; Mitsuyasu Kanai; Mikio Shoji; Kaoru Ikemoto; Mitsunori Morimatsu; Chikanori Hikasa; Kenji Nakashima

1999-01-01

68

Cerebrospinal fluid signs of neuronal damage after antiretroviral treatment interruption in HIV1 infection  

Microsoft Academic Search

BACKGROUND: The neurofilament is a major structural component of myelinated axons. Increased cerebrospinal fluid (CSF) concentrations of the light chain of the neurofilament protein (NFL) can serve as a sensitive indicator of central nervous system (CNS) injury. To assess whether interrupting antiretroviral treatment of HIV infection might have a deleterious effect on the CNS, we measured NFL levels in HIV-infected

Magnus Gisslén; Lars Rosengren; Lars Hagberg; Steven G Deeks; Richard W Price

2005-01-01

69

Volume Assessment of the Cerebrospinal Fluid Spaces for Computer Aided Diagnosis  

E-print Network

Volume Assessment of the Cerebrospinal Fluid Spaces for Computer Aided Diagnosis A. Lebret, E to provide support in the diagnosis of hydrocephalus, which requires an assessment to the volumes a fully automatic method to estimate the CSF volumes from a new 3D whole body MR imaging sequence

Paris-Sud XI, Université de

70

Normal pressure hydrocephalus. Influences on cerebral hemodynamic and cerebrospinal fluid pressure--chemical autoregulation  

Microsoft Academic Search

Blood flow in the cerebral gray matter was measured in normal pressure hydrocephalus and Alzheimer disease by 133Xe inhalation. Flow values in the frontal and temporal gray matter increased after lowering cerebrospinal fluid (CSF) pressure by lumbar puncture in normal pressure hydrocephalus (p less than 0.05) and also after shunting. One case with cerebral complications did not improve clinically. In

John S. Meyer; Hisao Tachibana; Jeffrey P. Hardenberg; Richard E. Dowell Jr.; Yasuhisa Kitagawa; Karl F. Mortel

1984-01-01

71

Cerebrospinal fluid flow and production in patients with normal pressure hydrocephalus studied by MRI  

Microsoft Academic Search

An interleaved velocity-sensitised fast low-angle shot pulse sequence was used to study cerebrospinal fluid (CSF) flow in the cerebral aqueduct, and supratentorial CSF production in 9 patients with normal pressure hydrocephalus (NPH) and 9 healthy volunteers. The peak aqueduct CSF flow, both caudal and rostral, was significantly increased in patients with NPH. No significant difference in the supratentorial CSF production

P. Gideon; F. Ståhlberg; C. Thomsen; F. Gjerris; P. S. Sørensen; O. Henriksen

1994-01-01

72

Normal and Hydrocephalic Brain Dynamics: The Role of Reduced Cerebrospinal Fluid Reabsorption in Ventricular Enlargement  

E-print Network

with communicating hydrocephalus. Mathematical brain models were created using the MRI images of normal subjects­structure interaction, Communicating hydrocephalus, Intracranial pressure. INTRODUCTION A more complete understandingNormal and Hydrocephalic Brain Dynamics: The Role of Reduced Cerebrospinal Fluid Reabsorption

Linninger, Andreas A.

73

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

Microsoft Academic Search

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

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

2005-01-01

74

Normal pressure hydrocephalus: Correlation between CT and measurements of cerebrospinal fluid dynamics  

Microsoft Academic Search

Summary Twenty-nine patients consecutively admitted for consideration of CSF diversion surgery for suspected communicating (“normal pressure”) hydrocephalus underwent cranial computerized tomography (CT) and study of cerebrospinal fluid (CSF) absorption, the latter determined as resistance to outflow of CSF (Ro). From the CT the size of the ventricular system was determined by various linear measurements and ratios and the presence of

M. Kosteljanetz; H. M. Ingstrup

1985-01-01

75

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

Microsoft Academic Search

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.

D. Oreškovi?; M. Klarica

2010-01-01

76

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

Microsoft Academic Search

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

D. Oreškovi?; M. Klarica

2011-01-01

77

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

Microsoft Academic Search

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

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

2006-01-01

78

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...

79

Rapid diagnosis of experimental meningitis by bacterial heat production in cerebrospinal fluid  

Microsoft Academic Search

BACKGROUND: Calorimetry is a nonspecific technique which allows direct measurement of heat generated by biological processes in the living cell. We evaluated the potential of calorimetry for rapid detection of bacterial growth in cerebrospinal fluid (CSF) in a rat model of bacterial meningitis. METHODS: Infant rats were infected on postnatal day 11 by direct intracisternal injection with either Streptococcus pneumoniae,

Andrej Trampuz; Andrea Steinhuber; Matthias Wittwer; Stephen L Leib

2007-01-01

80

Cerebrospinal fluid of patients administered moxifloxacin modulates the secretion of cytokines from human monocytes  

Microsoft Academic Search

To evaluate the ex vivo immunomodulatory properties of moxifloxacin, we applied serum and cerebrospinal fluid (CSF) samples from 50 patients who received a single oral dose of 400 mg. Patients were divided into 5 groups according to time lapsing between sampling and drug intake: group I, 0.5 to 1 h; group II, 1 to 2 h; group III, 2 to

Evangelos J. Giamarellos-Bourboulis; Emmanouel E. Douzinas; Thomas Tsaganos; Alexandra Pagoulatou; Olga Livaditi; Marianthi Vafiadou; Kyriaki Kanellakopoulou

2009-01-01

81

Oxytocin-messages via the cerebrospinal fluid: Behavioral effects; a review  

Microsoft Academic Search

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

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

2010-01-01

82

Evaluation of Tumor Marker S-100 in Cerebrospinal Fluid from Subjects with Nonischemic Brain Pathologies  

Microsoft Academic Search

In order to evaluate the S-100 concentration in cerebrospinal fluid from subjects with nonischemic brain damage, a total of 33 samples were analyzed: 11 from subjects in whom no organic disease could be found; 14 from patients with a diagnosis of lymphocytic or bacterial-fungal meningitis, and 8 from patients with acute lymphatic leukemia but no demonstrable signs of meningeal involvement.

Jose R. Infante; Miguel Torres-Avisbal; Antonio Martinez; Juan A. Vallejo; Cristobal Aguilera; Pablo Contreras; Ana Benitez; Jose M. Latre

2000-01-01

83

Microscopic Examination and Broth Culture of Cerebrospinal Fluid in Diagnosis of Meningitis  

Microsoft Academic Search

We reviewed the results of microscopic Gram stain examination and routine culture for 2,635 cerebrospinal fluid (CSF) samples processed in an adult hospital microbiology laboratory during 55 months. There were 56 instances of bacterial or fungal meningitis (16 associated with central nervous system (CNS) shunt infection), four infections adjacent to the subarachnoid space, four cases of sepsis without meningitis, and

SHERRY A. DUNBAR; RACHEL A. EASON; DANIEL M. MUSHER; JILL E. CLARRIDGE

1998-01-01

84

Value of cerebrospinal fluid examination in the diagnosis of meningitis in the newborn  

Microsoft Academic Search

Between 1 October 1988 and 30 September 1991 the results of all 896 cerebrospinal fluid examinations from 736 neonates were correlated with clinical diagnosis, treatment, and outcome. The prevalence of fungal or bacterial meningitis in babies requiring lumbar puncture was only 0.95%. Gram staining had a sensitivity of 68% and a positive predictive value of only 46% for the diagnosis

L Hristeva; I Bowler; R Booy; A King; A R Wilkinson

1993-01-01

85

Dosage of lactate in the cerebrospinal fluid in infectious diseases of the central nervous system  

Microsoft Academic Search

This paper analyzes the diagnosis aid of the dosage of lactate in the cerebrospinal fluid (CSF) in infectious diseases of the central nervous system (CNS). We analyzed prospectively 130 samples of CSF of 116 patients with diagnoses of infectious processes in the CNS. The 130 samples of CSF were divided into five groups: 28 samples of the control group, 40

Hideraldo Luis Souza Cabeça; Hélio Rodrigues Gomes; Luís dos Ramos Machado; José Antonio Livramento

2001-01-01

86

Two dimensional difference gel electrophoresis analysis of cerebrospinal fluid in tuberculous meningitis patients  

Microsoft Academic Search

Tuberculous meningitis (TBM) is a serious complication of tuberculosis that affects the central nervous system. Present methods to diagnose TBM are not suitable for early diagnosis. Molecular markers and sensitive methods to identify them in the early stage of infection of TBM are critically needed for efficient management. We have done the proteomic analysis of TBM cerebrospinal fluid (n=20) with

Jitender Kataria; Lokesh A. Rukmangadachar; Gururao Hariprasad; Jithesh O; Manjari Tripathi; Alagiri Srinivasan

2011-01-01

87

Axon Reactive B Cells Clonally Expanded in the Cerebrospinal Fluid of Patients with Multiple Sclerosis  

Microsoft Academic Search

Demyelination and axonal loss have been described as the histological hallmarks of inflammatory lesions of multiple sclerosis (MS) and are the pathological correlates of persistent disability. However, the immune mechanisms underlying axonal damage in MS remain unknown. Here, we report the use of single chain-variable domain fragments (scFv) from clonally expanded cerebrospinal fluid (CSF) B cells to show the role

Yiping Zhang; Reng-Rong Da; Wenzhong Guo; Hui-Min Ren; Lutz G. Hilgenberg; Raymond A. Sobel; Wallace W. Tourtellotte; Martin A. Smith; Michael Olek; Sudhir Gupta; Richard T. Robertson; Rashed Nagra; Stanley Van Den Noort; Yufen Qin

2005-01-01

88

Tissue inhibitors of matrix metalloproteinases are elevated in cerebrospinal fluid of neurodegenerative diseases  

Microsoft Academic Search

Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of diseases such as Alzheimer's Disease (AD) and amyotrophic lateral sclerosis (ALS). Increased expression of MMP-9 and TIMPs has been reported in postmortem AD and ALS brain tissue, as well as in ALS cerebrospinal fluid (CSF) and plasma. Although individual studies of MMP and TIMP expression in CSF have included AD and

S Lorenzl; D. S Albers; P. A LeWitt; J. W Chirichigno; S. L Hilgenberg; M. E Cudkowicz; M. F Beal

2003-01-01

89

Myelin basic protein in cerebrospinal fluid: a predictive marker of delayed encephalopathy from carbon monoxide poisoning  

Microsoft Academic Search

This study was designed to investigate whether myelin basic protein (MBP) in cerebrospinal fluid (CSF) can be a predictive marker of delayed encephalopathy from carbon monoxide (CO) poisoning. Five patients with CO poisoning were included in the study. The CSF was serially sampled to determine the MBP concentration. All patients were classified into group DE or group non-DE according to

Toshimitsu Ide; Yoshito Kamijo

2008-01-01

90

Proposal of “evolution theory in cerebrospinal fluid dynamics” and minor pathway hydrocephalus in developing immature brain  

Microsoft Academic Search

Background  The specificity of cerebrospinal fluid (CSF) dynamics in the immature brain still remains unknown. In our data previously published, the transependymal intraparenchymal CSF pathway (the minor pathway) plays a significant role in various degrees in the alternative CSF passage. Now, there is a growing consensus in the age differences in the outcome of neuroendoscopic ventriculostomy in treatment of non-communicating types

Shizuo Oi; Concezio Di Rocco

2006-01-01

91

Posttraumatic lumbar cerebrospinal fluid leak: detection by retrograde In-111-DTPA myeloscintography  

SciTech Connect

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.

Colletti, P.M.; Siegel, M.E.

1981-09-01

92

Prediction of bacterial meningitis based on cerebrospinal fluid pleocytosis in children.  

PubMed

Children with cerebrospinal fluid pleocytosis are frequently treated with parenteral antibiotics, but only a few have bacterial meningitis. Although some clinical prediction rules, such as bacterial meningitis score, are of well-known value, the cerebrospinal fluid white blood cells count can be the initial available information. Our aim was to establish a cutoff point of cerebrospinal fluid white blood cell count that could distinguish bacterial from viral and aseptic meningitis. A retrospective study of children aged 29 days to 17 years who were admitted between January 1st and December 31th, 2009, with cerebrospinal fluid pleocytosis (white blood cell?7?L(-1)) was conducted. The cases of traumatic lumbar puncture and of antibiotic treatment before lumbar puncture were excluded. There were 295 patients with cerebrospinal fluid pleocytosis, 60.3% females, medium age 5.0±4.3 years distributed as: 12.2% 1-3 months; 10.5% 3-12 months; 29.8% 12 months to 5 years; 47.5% >5 years. Thirty one children (10.5%) were diagnosed with bacterial meningitis, 156 (52.9%) viral meningitis and 108 (36.6%) aseptic meningitis. Bacterial meningitis was caused by Neisseria meningitidis (48.4%), Streptococcus pneumoniae (32.3%), other Streptococcus species (9.7%), and other agents (9.7%). cerebrospinal fluid white blood cell count was significantly higher in patients with bacterial meningitis (mean, 4839cells/?L) compared to patients with aseptic meningitis (mean, 159cells/?L, p<0.001), with those with aseptic meningitis (mean, 577cells/?L, p<0.001) and with all non-bacterial meningitis cases together (p<0.001). A cutoff value of 321white blood cell/?L showed the best combination of sensitivity (80.6%) and specificity (81.4%) for the diagnosis of bacterial meningitis (area under receiver operating characteristic curve 0.837). Therefore, the value of cerebrospinal fluid white blood cell count was found to be a useful and rapid diagnostic test to distinguish between bacterial and nonbacterial meningitis in children. PMID:23602468

Águeda, Sofia; Campos, Teresa; Maia, Ana

2013-01-01

93

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

PubMed Central

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

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

94

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

PubMed

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

Reid; Kilduff; Romero; Florant; Dement; Heller

1992-03-01

95

Stasis in Aristotle's rhetoric  

Microsoft Academic Search

Analysis of Aristotle's contributions to the development of stasis is incomplete unless a study of the Rhetoric is included. Although books i and ii of the Rhetoric contain only two passages that are even possibly early forms of stasis, book Hi includes stasis as a system of analysis. The doctrine, however, lacks the clear, precise formulation found later in Hermagoras,

Wayne N. Thompson

1972-01-01

96

Increased cerebrospinal fluid interleukin-8 in bipolar disorder patients associated with lithium and antipsychotic treatment.  

PubMed

Inflammation has been linked to the pathophysiology of bipolar disorder based on studies of inflammation markers, such as cytokine concentrations, in plasma and serum samples from cases and controls. However, peripheral measurements of cytokines do not readily translate to immunological activity in the brain. The aim of the present study was to study brain immune and inflammatory activity. To this end, we analyzed cytokines in cerebrospinal fluid from 121 euthymic bipolar disorder patients and 71 age and sex matched control subjects. Concentrations of 11 different cytokines were determined using immunoassays. Cerebrospinal fluid IL-8 concentrations were significantly higher in patients as compared to controls. The other cytokines measured were only detectable in part of the sample. IL-8 concentrations were positively associated to lithium- and antipsychotic treatment. The findings might reflect immune aberrations in bipolar disorder, or be due to the effects of medication. PMID:25451615

Isgren, Anniella; Jakobsson, Joel; Pålsson, Erik; Ekman, Carl Johan; Johansson, Anette G M; Sellgren, Carl; Blennow, Kaj; Zetterberg, Henrik; Landén, Mikael

2015-01-01

97

Postmortem Cerebrospinal Fluid Pleocytosis: A Marker of Inflammation or Postmortem Artifact?  

PubMed Central

The aim of this paper is to reassess the significance of postmortem cerebrospinal fluid pleocytosis. Published articles of CSF changes after death were reviewed, and reanalysis, in the light of modern views on the significance of bacterial postmortem isolates, was undertaken. There is theoretical and experimental evidence that the blood brain barrier to the movement of protein and cells is preserved in the first few hours after death. The number of mononuclear cells in the cerebrospinal fluid does rise in the first 24 hours after death, and this is most probably due to detachment of leptomeningeal lining cells. But the marked increase in lymphocyte counts seen in some cases of sudden infant death syndrome (SIDS) and in other deaths in the paediatric age range could well be a marker of inflammation. PMID:22518189

Morris, James A.; Harrison, Linda M.; Telford, David R.

2012-01-01

98

[Reference values in the cerebrospinal fluid of calves between four and eight weeks of age].  

PubMed

Reference values for the following parameters were established in the cerebrospinal fluid of 27 calves between four and eight weeks of age: specific weight, protein concentration, erythrocyte count, total leucocyte count with cell differentiation, creatin kinase activity, glucose and sodium. If possible, the findings were compared with those of other authors in calves and adult bovines. With 24.3 cells per microliter the 90% quantile of the total leucocyte count was seated significantly above comparable values for adult bovines. Hence, in individual cases markedly higher leucocyte counts can be expected in the cerebrospinal fluid of calves. In agreement with other authors, the protein concentration in calves was lower than in adult bovines. The reference range for creatin kinase activity was increased whereas the one for sodium was only slightly increased compared to earlier investigations in calves and in adult bovines. PMID:12125239

Stocker, H; Sicher, D; Rüsch, P; Lutz, H

2002-06-01

99

Primary Spontaneous Cerebrospinal Fluid Leaks and Idiopathic Intracranial Hypertension  

PubMed Central

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

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

2014-01-01

100

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

PubMed

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

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

2014-10-01

101

Cyclophosphamide plasma and cerebrospinal fluid kinetics with and without dimethyl sulfoxide  

Microsoft Academic Search

Ten patients with brain tumors and indwelling ventricular reservoirs were pretreated with 5% to 10% dimethyl sulfoxide (DMSO) (intravenous, oral, or both) and were then treated with 1.0 to 1.25 gm\\/m2 cyclophosphamide (CYC). All patients were also on anticonvulsants and dexamethasone. CYC and alkylating activity (alk act) in plasma and concomitant ventricular cerebrospinal fluid (CSF) were measured by gas chromatography

Merrill J Egorin; Richard S Kaplan; Michael Salcman; Joseph Aisner; Michael Colvin; Peter H Wiernik; Nicholas R Bachur

1982-01-01

102

Glutamate enhances brain damage and albumin content in cerebrospinal fluid after intracarotid protamine infusion  

Microsoft Academic Search

The blood-brain barrier was opened by intracarotid infusion of 5 mg protamine sulfate in 100 µl 0.9% NaCl over a period of 30 s either alone or followed by infusion of 10 mg L-glutamate in 0.9% NaCl. Glutamate alone was infused in four control rats. Cisternal cerebrospinal fluid (CSF) was withdrawn before protamine administration and before the brains were fixed

Irena Westergren; Claes Nordborg; Barbro B. Johansson

1993-01-01

103

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

PubMed Central

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

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

2014-01-01

104

5-Hydroxyindoleacetic Acid Levels in the Cerebrospinal Fluid of Depressive Patients treated with Probenecid  

Microsoft Academic Search

ACCORDING to the serotonin (5-hydroxytryptamine, 5-HT) hypothesis there is a causal relationship between mental depression and 5-HT deficiency in the brain1-3. Some depressive patients-mainly those suffering from an endogenous depression-display the following clinical signs. (1) The concentration of 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) (refs. 4 and 5) and the urinary concentrations of 5-HT (ref. 6) and 5-HIAA

H. M. van Praag; J. Korf; J. Puite

1970-01-01

105

New PCR assay for rapid and quantitative detection of human cytomegalovirus in cerebrospinal fluid.  

PubMed Central

Rapid Chelex extraction combined with an automated hybridization assay for the detection of PCR-amplified human cytomegalovirus DNA from cerebrospinal fluid was established. Quantitation of DNA was performed with a plasmid being used as an external standard. The detection limit was 10 copies per microliter. Quantitative detection of human cytomegalovirus DNA could be achieved over a range from 10 to 10(4) copies per microliter. PMID:8789047

Vogel, J U; Cinatl, J; Lux, A; Weber, B; Driesel, A J; Doerr, H W

1996-01-01

106

Tamoxifen Paradoxically Decreases Paclitaxel Deposition into Cerebrospinal Fluid of Brain Tumor Patients  

Microsoft Academic Search

Summary  Background: P-glycoprotein (Pgp) mediates, in part, resistance to natural product chemotherapy drugs which constitute over half of the\\u000a available drugs for cancer treatment. Tamoxifen (TAM) enhances intracellular deposition of natural product chemotherapy in\\u000a human cell lines by inhibition of Pgp. Pgp is highly expressed in the choroid plexus and is thought to be a key component\\u000a of the blood–cerebrospinal fluid

Johnson Chen; Casilda Balmaceda; Jeffrey N. Bruce; Michael B. Sisti; May Huang; Ying Kuen K. Cheung; Guy M. McKhann; Robert R. Goodman; Robert L. Fine

2006-01-01

107

Western blot analysis of cerebrospinal fluid for detection of Aspergillus antigens  

Microsoft Academic Search

Western-blot immunoassay of cerebrospinal fluid (CSF) specimens of patients with central nervous system (CNS) aspergillosis\\u000a (3), CNS candidosis (1) and bacterial meningitis (2) was carried out using pooled serum from histopathologically proven deep-seated\\u000a aspergillosis cases to detect unique antigenic fractions for aspergillosis in CSF. No reactivity was observed in patients\\u000a with non-fungal meningitis. Four cross-reactive bands (40, 90, 200 and

Pallab Ray; Arunaloke Chakrabarti; Manu Jatana; B. S. Sharma; A. Pathak

1995-01-01

108

Neonatal Candida meningitis: significance of cerebrospinal fluid parameters and blood cultures  

Microsoft Academic Search

Objective:The purpose of this study was to examine the frequency of normal cerebrospinal fluid (CSF) parameters in Candida meningitis and the proportion of candidemia associated with Candida meningitis.Study design:We evaluated the initial lumbar puncture results from infants discharged from 150 Neonatal Intensive Care Units between 1997 and 2004. Candida meningitis was diagnosed by a positive CSF culture or positive Gram

M Cohen-Wolkowiez; P B Smith; B Mangum; W J Steinbach; B D Alexander; C M Cotten; R H Clark; T J Walsh; D K Benjamin

2007-01-01

109

Gene Transfer of Extracellular Superoxide Dismutase Increases Superoxide Dismutase Activity in Cerebrospinal Fluid  

Microsoft Academic Search

Background and Purpose—Copper-zinc superoxide dismutase (CuZnSOD) is expressed intracellularly, while extracel- lular SOD (EC-SOD) is released from cells. The purpose of this study was to determine whether gene transfer of CuZnSOD increases SOD activity predominantly in tissues, and gene transfer of EC-SOD increases SOD activity in cerebrospinal fluid (CSF). We also determined whether heparin or dextran sulfate releases EC-SOD into

Hiroshi Nakane; Yi Chu; Frank M. Faraci; Larry W. Oberley; Donald D. Heistad

110

Determination of haem derivatives in the cerebrospinal fluid--a semi-quantitative method.  

PubMed Central

A spectrophotometric method for semi-quantitative determination of oxyhaemoglobin, methaemoglobin and bilirubin in the cerebrospinal fluid is described and evaluated. The method involves correction for CSF protein. It is based on absorbance registrations on three wavelengths; 400, 420 and 470 nm. Reference values for a healthy control group and a hyperbilirubinaemic group are presented. Evaluation of the method shows that it is well suited to semi-quantitative determination of haem derivatives in the CSF. PMID:6886704

Wahlgren, N G; Bergström, K

1983-01-01

111

Cerebrospinal fluid and plasma testosterone levels in post-traumatic stress disorder and tobacco dependence  

Microsoft Academic Search

Background: Little is known about the relationship between endogenous central nervous system (CNS) testosterone and any psychiatric syndrome. The goal of this study was to screen for potential abnormalities in CNS testosterone levels in patients with post-traumatic stress disorder (PTSD) and\\/or tobacco dependence.Methods: We sampled cerebrospinal fluid (CSF) via a subarachnoid catheter over six hours and determined hourly basal CSF

J. Jeffrey Mulchahey; Nosa N. Ekhator; Hong Zhang; John W. Kasckow; Dewleen G. Baker; Thomas D. Geracioti

2001-01-01

112

Dexamethasone, Cerebrospinal Fluid Matrix Metalloproteinase Concentrations and Clinical Outcomes in Tuberculous Meningitis  

Microsoft Academic Search

BackgroundAdjunctive dexamethasone reduces mortality from tuberculous meningitis, but how it produces this effect is not known. Matrix metalloproteinases (MMPs) are important in the immunopathology of many inflammatory CNS diseases thus we hypothesized that that their secretion is important in TBM and might be influenced by dexamethasone.Methodology\\/Principal FindingsThe kinetics of cerebrospinal fluid (CSF) MMP and tissue inhibitors of MMPs (TIMPs) concentrations

Justin A. Green; Chau T. H. Tran; Jeremy J. Farrar; Mai T. H. Nguyen; Phu H. Nguyen; Sinh X. Dinh; Nghia D. T. Ho; Chuong V. Ly; Hien T. Tran; Jon S. Friedland; Guy E. Thwaites

2009-01-01

113

Cerebrospinal fluid flow dynamics in patients with multiple sclerosis: a phase contrast magnetic resonance study  

PubMed Central

Cerebrospinal fluid (CSF) flow dynamics, which supposedly have a strong relationship with chronic cerebrospinal venous insufficiency (CCSVI), might be expected to be affected in multiple sclerosis (MS) patients. In this study, CSF flow at the level of the cerebral aqueduct was evaluated quantitatively by phase contrast magnetic resonance imaging (PC-MRI) to determine whether CSF flow dynamics are affected in MS patients. We studied 40 MS patients and 40 healthy controls using PC-MRI. We found significantly higher caudocranial (p=0.010) and craniocaudal CSF flow volumes (p=0.015) and stroke volume (p=0.010) in the MS patients compared with the controls. These findings may support the venous occlusion theory, but may also be explained by atrophy-dependent ventricular dilatation independent of the venous theory in MS patients. PMID:22364942

Gorucu, Yasin; Albayram, Sait; Balci, Belgin; Hasiloglu, Zehra Isik; Yenigul, Kubilay; Yargic, Fatma; Keser, Zafer; Kantarci, Fatih; Kiris, Adem

114

Cerebrospinal fluid flow imaging by using phase-contrast MR technique  

PubMed Central

Cerebrospinal fluid (CSF) spaces include ventricles and cerebral and spinal subarachnoid spaces. CSF motion is a combined effect of CSF production rate and superimposed cardiac pulsations. Knowledge of CSF dynamics has benefited considerably from the development of phase-contrast (PC) MRI. There are several disorders such as communicating and non-communicating hydrocephalus, Chiari malformation, syringomyelic cyst and arachnoid cyst that can change the CSF dynamics. The aims of this pictorial review are to outline the PC MRI technique, CSF physiology and cerebrospinal space anatomy, to describe a group of congenital and acquired disorders that can alter the CSF dynamics, and to assess the use of PC MRI in the assessment of various central nervous system abnormalities. PMID:21586507

Battal, B; Kocaoglu, M; Bulakbasi, N; Husmen, G; Tuba Sanal, H; Tayfun, C

2011-01-01

115

Fluoride in cerebrospinal fluid of patients with fluorosis.  

PubMed Central

The CSF fluoride level of individuals drinking water with normal fluoride content and of patients with endemic fluorosis were studied. For the purpose of studying the relationship between the dynamic equilibrium of the CSF fluoride and other body fluids, urine and blood fluoride were examined simultaneously. Fluoride was revealed in every CSF sample of the control group and its mean value was lower than that of the blood. The CSF fluoride concentration of patients with fluorosis was slightly higher than that of the control group, although there was no statistically significant difference. The results suggests that fluoride is a normal component of CSF. In severe cases of fluorosis or breakdown of the blood-brain in some diseases of the central nervous system, the CSF fluoride value might be increased. PMID:3221229

Hu, Y H; Wu, S S

1988-01-01

116

Definitive Diagnosis of Cerebrospinal Fluid Leak Into the Pleural Space Using 111In-DTPA Cisternography.  

PubMed

A 58-year-old woman with a calcified disk extrusion causing severe spinal stenosis underwent T8 to T9 diskectomy and spinal fusion. A postoperative pseudomeningocele was treated with lumbar drain and fibrin glue. Performed for persistent right pleural effusion, CT myelogram failed to show communication between the cerebrospinal fluid (CSF) and pleural space-even on 2-hour delayed images. Subsequent In-DTPA cisternogram clearly demonstrated CSF leakage into the right pleural space at 2 hours, and surgical repair yielded good results. Radionuclide cisternography is a highly useful method to detect CSF leak, especially when it is occult on CT yet suspected clinically. PMID:25243944

Howard, Brandon A; Gray, Linda; Isaacs, Robert E; Borges-Neto, Salvador

2014-09-18

117

Spontaneous Intracranial Hypotension with Magnetic Resonance Localisation of Spinal Cerebrospinal Fluid Leak  

PubMed Central

To increase the awareness of spontaneous intracranial hypotension (SIH), we report in this paper a middle-aged woman who presented with an intractable headache that worsened in sitting and standing positions (a postural headache). Magnetic resonance imaging (MRI) of the spine demonstrated a cerebrospinal fluid (CSF) leak at the level of the cervical spine, in addition to typical features in a brain MRI, including symmetrical subdural collections, circumferential dural enhancement and features of midbrain sagging. The patient underwent a surgical repair of the cervical CSF leak which resulted in a dramatic symptomatic improvement that was confirmed by follow-up imaging. PMID:24273678

Al-Brashdi, Yahya H.; Raniga, Sameer; Revati, Sharma R.

2013-01-01

118

Demonstration of Cerebrospinal Fluid Leakage on Radionuclide Cisternography by SPECT/CT.  

PubMed

We report a case of a 37-year-old woman with severe headache provoked by postural changes who was referred to the nuclear medicine department for radionuclide cisternography to demonstrate suspected cerebrospinal fluid leakage. There was an increased uptake laterally on the left paraspinal region of upper thoracal spine and posteriorly on the upper cervical region. Fused SPECT/CT images located the exact leakage site as at the first costovertebral junction level on the left side laterally and on the posterior region of the first and second cervical spine. The treatment with epidural blood patch was successful. PMID:25072925

Nursal, Gül Nihal; Yapar, Ali Fuat

2015-01-01

119

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

SciTech Connect

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.

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

1990-09-01

120

Maraviroc-containing regimen suppresses HIV replication in the cerebrospinal fluid of patients with neurological symptoms.  

PubMed

We report the concentrations of maraviroc in the cerebrospinal fluid (CSF) and plasma of six HIV-1-infected patients with both neurological impairment and detectable HIV-1 replication in CSF. One month after starting maraviroc, the viral load in the CSF decreased significantly (P = 0.005). The median (range) maraviroc concentration in plasma was 347 ng/ml (123-2678). Four patients had CSF concentrations above the protein-adjusted inhibitory concentration (IC90) of 0.57 ng/ml (0.06-10.7) with a median of 102 ng/ml (35-173). PMID:20601852

Melica, Giovanna; Canestri, Ana; Peytavin, Gilles; Lelievre, Jean D; Bouvier-Alias, Magali; Clavel, Cyril; Calvez, Vincent; Lascaux, Anne S; Katlama, Christine; Levy, Yves

2010-08-24

121

A tomographic study of the skull base in primary spontaneous cerebrospinal fluid leaks  

Microsoft Academic Search

Introduction  This study aims to evaluate the existence of anatomic abnormalities in the skull base that could contribute to the origin\\u000a of primary spontaneous cerebrospinal fluid leaks (PSL).\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Twenty PSL patients were compared with 20 healthy individuals. The following features were measured through an analysis of\\u000a computed tomography scans: the angles of the petrosal bones and skull base in both the

Alexandre Varella Giannetti; Roberto Eustáquio S. Guimarães; Ana Paula M. S. Santiago; Francisco Otaviano L. Perpétuo; Marco Antônio O. Machado

122

Non Invasive Microwave Sensor for the Detection of Lactic Acid in Cerebrospinal Fluid (CSF)  

NASA Astrophysics Data System (ADS)

This research involves the use of a low power microwave sensor for analysis of lactic acid in cerebrospinal fluid (CSF), an indicator of neurological impairment during aortic aneurysm surgery which could provide the basis for improved treatment regimes and better quality of care with more efficient use of resources. This paper presents initial work using standard lactate curves in water followed by lactate in "synthetic CSF". A multi-modal spectral signature has been defined for lactate, forming the basis for subsequent development of microwave sensor platform that is able to detect concentrations of lactic acid in CSF of volumes less than 1ml.

Goh, J. H.; Mason, A.; Al-Shamma'a, A. I.; Field, M.; Shackcloth, M.; Browning, P.

2011-08-01

123

Digital PCR technology detects brain-tumor-associated mutation in cerebrospinal fluid  

Cancer.gov

Researchers from the Massachusetts General Hospital (a component of the Dana-Farber Cancer Institute) and their colleagues have used digital versions of a standard molecular biology tool to detect a common tumor-associated mutation in the cerebrospinal fluid (CSF) of patients with brain tumors. In their report being published in the open-access journal Molecular Therapy – Nucleic Acids, the investigators describe using advanced forms of the gene-amplification technology polymerase chain reaction (PCR) to analyze bits of RNA carried in membrane-covered sacs called extracellular vesicles for the presence of a tumor-associated mutation in a gene called IDH1.

124

Cerebrospinal fluid concentrations of neuropeptide Y in depressed patients and in controls.  

PubMed Central

Concentrations of Neuropeptide Y-like (NPY-LI) immunoreactivity in cerebrospinal fluid (CSF) were measured in a group of depressed patients (n = 24) and compared with that of control subjects (n = 12). CSF-NPY-LI was significantly reduced in the group of non-endogenously depressed patients when classified according to Newcastle Rating Scale for Depression--1971 (N-II). No significant correlation was found in the control or depressed groups between lumbar concentrations of NPY-LI and a number of other neurotransmitters. PMID:1349825

Gjerris, A; Widerlöv, E; Werdelin, L; Ekman, R

1992-01-01

125

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

PubMed Central

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

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

2014-01-01

126

Cerebrospinal fluid sphingolipids, ?-amyloid, and tau in adults at risk for Alzheimer's disease.  

PubMed

Cellular studies suggest sphingolipids may cause or accelerate amyloid-beta (A?) and tau pathology but in vivo human studies are lacking. We determined cerebrospinal fluid levels of sphingolipids (ceramides and sphingomyelins), amyloid-beta (A?1-42, A?X-38, A?X-40, and A?X-42) and tau (T-tau and p-tau181) in 91 cognitively normal individuals, aged 36-69 years, with a parental history of Alzheimer's disease. The 18-carbon acyl chain length ceramide species was associated with A?X-38 (r = 0.312, p = 0.003), A?X-40 (r = 0.327, p = 0.002), and T-tau (r = 0.313, p = 0.003) but not with A?X-42 (r = 0.171, p = 0.106) or p-tau (r = 0.086, p = 0.418). All sphingomyelin species correlated (most p < 0.001) with all A? species and T-tau; many also correlated with p-tau. Results remained in regression models after controlling for age and APOE genotype. These results suggest in vivo relationships between cerebrospinal fluid ceramides and sphingomyelins and A? and tau levels in cognitively normal individuals at increased risk for Alzheimer's disease, indicating these sphingolipids may be associated with early pathogenesis. PMID:24952994

Mielke, Michelle M; Haughey, Norman J; Bandaru, Veera V R; Zetterberg, Henrik; Blennow, Kaj; Andreasson, Ulf; Johnson, Sterling C; Gleason, Carey E; Blazel, Hanna M; Puglielli, Luigi; Sager, Mark A; Asthana, Sanjay; Carlsson, Cynthia M

2014-11-01

127

Detection of Haemophilus influenzae in cerebrospinal fluids by polymerase chain reaction DNA amplification.  

PubMed

Two primer sets were chosen for the detection of Haemophilus influenzae in cerebrospinal fluid by polymerase chain reaction (PCR) DNA amplification. One primer set was selected from sequences encoding a capsulation-associated protein and reacted with target DNA from all 15 capsulate H. influenzae strains (all serotypes) examined. The other primer set was selected from the DNA sequence of a gene encoding for outer-membrane protein P6 and reacted with the 15 capsulate and 10 non-capsulate strains of H. influenzae tested. This primer set also reacted with the closely related species H. haemolyticus and H. aegyptius, and with two of nine H. parainfluenzae strains. In reconstruction experiments, PCR DNA amplification was able to detect as few as five H. influenzae cells when 40 cycles of amplification were used. Two hundred cerebrospinal fluid (CSF) samples collected consecutively from patients suffering from meningitis were investigated by PCR; 40 were culture-positive for H. influenzae and 39 of these were also clearly positive in the PCR test with both primer sets. Contamination occurred to some extent with 40 cycles of amplification but was completely eliminated when the number of cycles was reduced to 35. We conclude that the two primer sets are appropriate for the detection of H. influenzae by PCR, each having its own specificity. When these two primer sets are used, PCR is a technique of equivalent sensitivity to culture for the detection of H. influenzae in CSF. PMID:2258914

van Ketel, R J; de Wever, B; van Alphen, L

1990-12-01

128

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

PubMed

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

Li, Jingwei; Feng, Liang; Jiang, Xinguo

2015-02-01

129

Cerebrospinal Fluid Prohormone Processing and Neuropeptides Stimulating Feed Intake of Dairy Cows during Early Lactation.  

PubMed

After parturition, feed intake of dairy cows increases within the first weeks of lactation, but the molecular mechanisms stimulating or delaying the slope of increase are poorly understood. Some of the molecules controlling feed intake are neuropeptides that are synthesized as propeptides and subsequently processed before they bind to specific receptors in feeding centers of the brain. Cerebrospinal fluid surrounds most of the feed intake regulatory centers and contains numerous neuropeptides. In the present study, we used a proteomic approach to analyze the neuropeptide concentrations in cerebrospinal fluid taken from dairy cows between day -18 and -10, and between day +10 and +20 relative to parturition. We found 13 proteins which were only present in samples taken before parturition, 13 proteins which were only present in samples taken after parturition, and 25 proteins which were commonly present, before and after parturition. Among them, differences in pro-neuropeptide Y, proenkephalin-A, neuroendocrine convertase-2, neurosecretory protein VGF, chromogranin-A, and secretogranin-1 and -3 concentrations relative to parturition highlight propeptides and prohormone processings involved in the control of feed intake and energy homeostasis. Scaffold analysis further emphasized an increased tone of endogenous opioids associated with the postparturient increase of feed intake. PMID:25547169

Kuhla, Björn; Laeger, Thomas; Husi, Holger; Mullen, William

2015-02-01

130

COX-2 drives metastatic breast cells from brain lesions into the cerebrospinal fluid and systemic circulation.  

PubMed

Breast cancer is among the most common malignancies that metastasize to the brain, with 15% to 20% of patients with metastatic breast cancer eventually developing brain metastases. We previously reported a method to enumerate tumor cells in the cerebrospinal fluid (CSF) of patients with breast cancer with central nervous system (CNS) metastases, a setting that lacks sufficiently informative biomarkers. Here, we show that breast cancer cells can spontaneously disseminate into the CSF from brain lesions in mice in a COX-2-dependent manner and can escape from the CNS to systemic circulation. Enumeration of tumor cells in the peripheral blood (circulating tumor cells, CTC) and CSF (cerebrospinal fluid tumor cells, CSFTC) of nine breast cancer patients with brain metastases revealed dynamic changes in tumor cell burden in both the peripheral blood and CSF compartments that correlated with clinical disease progression. Interestingly, four of the enrolled patients exhibited rapid intercompartmental transitioning of the disease reflected in the CTC and CSFTC counts that preceded corresponding evidence by clinical imaging or neurologic symptoms. Two of these patients had systemic disease recurrence involving the primary malignant site. Intercompartmental cycling of tumor cells may represent an important mechanism for disease persistence and recurrence that may involve tumor self-seeding. Our findings demonstrate the involvement of COX-2 in the genesis of CSFTCs and suggest that COX-2 inhibitors should be investigated in patients with breast cancer with brain metastases for their ability to reduce CSFTC counts and prevent systemic recurrence. PMID:24614081

Allen, Joshua E; Patel, Akshal S; Prabhu, Varun V; Dicker, David T; Sheehan, Jonas M; Glantz, Michael J; El-Deiry, Wafik S

2014-05-01

131

GWAS of cerebrospinal fluid tau levels identifies risk variants for Alzheimer's disease.  

PubMed

Cerebrospinal fluid (CSF) tau, tau phosphorylated at threonine 181 (ptau), and A??? are established biomarkers for Alzheimer's disease (AD) and have been used as quantitative traits for genetic analyses. We performed the largest genome-wide association study for cerebrospinal fluid (CSF) tau/ptau levels published to date (n = 1,269), identifying three genome-wide significant loci for CSF tau and ptau: rs9877502 (p = 4.89 × 10?? for tau) located at 3q28 between GEMC1 and OSTN, rs514716 (p = 1.07 × 10?? and p = 3.22 × 10?? for tau and ptau, respectively), located at 9p24.2 within GLIS3 and rs6922617 (p = 3.58 × 10?? for CSF ptau) at 6p21.1 within the TREM gene cluster, a region recently reported to harbor rare variants that increase AD risk. In independent data sets, rs9877502 showed a strong association with risk for AD, tangle pathology, and global cognitive decline (p = 2.67 × 10??, 0.039, 4.86 × 10??, respectively) illustrating how this endophenotype-based approach can be used to identify new AD risk loci. PMID:23562540

Cruchaga, Carlos; Kauwe, John S K; Harari, Oscar; Jin, Sheng Chih; Cai, Yefei; Karch, Celeste M; Benitez, Bruno A; Jeng, Amanda T; Skorupa, Tara; Carrell, David; Bertelsen, Sarah; Bailey, Matthew; McKean, David; Shulman, Joshua M; De Jager, Philip L; Chibnik, Lori; Bennett, David A; Arnold, Steve E; Harold, Denise; Sims, Rebecca; Gerrish, Amy; Williams, Julie; Van Deerlin, Vivianna M; Lee, Virginia M-Y; Shaw, Leslie M; Trojanowski, John Q; Haines, Jonathan L; Mayeux, Richard; Pericak-Vance, Margaret A; Farrer, Lindsay A; Schellenberg, Gerard D; Peskind, Elaine R; Galasko, Douglas; Fagan, Anne M; Holtzman, David M; Morris, John C; Goate, Alison M

2013-04-24

132

The Aicardi-Goutières syndrome (familial, early onset encephalopathy with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis).  

PubMed Central

Aicardi-Goutières syndrome (Mendelian inheritance in man Catalog No *225750) is an autosomal recessive encephalopathy which causes developmental arrest, intracerebral calcification, and white matter disease in the presence of chronic cerebrospinal fluid lymphocytosis, and a raised level of cerebrospinal fluid interferon-alpha (IFN-alpha). Diagnosis requires the presence of progressive encephalopathy with onset shortly after birth, and characteristic clinical neurological and neuroimaging signs together with chronic CSF lymphocytosis. The syndrome has superficial resemblance to the neurological sequelae of congenital infection, thus a rigorous search for microbiological and serological evidence of embryopathic infections should be carried out in each case. Images PMID:8592332

Tolmie, J L; Shillito, P; Hughes-Benzie, R; Stephenson, J B

1995-01-01

133

The effect of serial in vitro haemodilution with maternal cerebrospinal fluid and crystalloid on thromboelastographic (TEG(®) ) blood coagulation parameters, and the implications for epidural blood patching.  

PubMed

Epidural blood patches may be used to treat post-dural puncture headache following accidental dural puncture in parturients. Their mode of action and the optimum volume of blood for injection remain controversial, with the interaction between injected blood and cerebrospinal fluid unknown. We aimed to establish the effects of serial haemodilution of whole blood with cerebrospinal fluid from 34 pregnant patients compared with serial haemodilution with Hartmann's solution, using the thromboelastogram. Haemodilution with either cerebrospinal fluid or Hartmann's solution had significant procoagulant and clot destabilising effects, enhanced with progressive haemodilution up to 30%. The effect of cerebrospinal fluid was greater compared with Hartmann's solution (p < 0.001). Cerebrospinal fluid led to a mean (95% CI) decrease in r-time by 2.4 (1.6-3.2) min, a decrease in k-time by 0.6 (0.4-0.8) min, an increase in alpha angle by 7.3 (5.5-9.0)°, and a decrease in maximum amplitude by 2.0 (0.6-3.4) mm. This may have implications for epidural blood patch, as success may be reduced near the time of dural puncture when cerebrospinal fluid leak is at its greatest, and large volumes of blood may be required to reduce haemodilution and clot destabilisation by cerebrospinal fluid. In addition, blood patching should be performed at the level of the dural puncture in order to ensure that the maximum volume of blood comes into contact with the cerebrospinal fluid. PMID:25428777

Armstrong, S; Fernando, R; Tamilselvan, P; Stewart, A; Columb, M

2015-02-01

134

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

PubMed

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

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

2011-01-01

135

Blood-cerebrospinal fluid barrier dysfunction in patients with bipolar disorder in relation to antipsychotic treatment.  

PubMed

Blood-cerebrospinal barrier (BCB) dysfunction has previously been shown in subjects with schizophrenia and depressed patients with attempted suicide. Bipolar disorder (BPD) shares clinical features with both these disorders, but it is unknown if the integrity of the BCB is altered also in BPD. To assess if BCB function in BPD we surveyed 134 mood-stabilized BPD patients and 86 healthy controls. Serum and cerebrospinal fluid (CSF) samples were collected and analyzed for albumin concentration by immunonephelometry. CSF/serum albumin ratio, an established measure of BCB function, was significantly elevated in BPD patients as compared to controls. After stratifying patients according to diagnostic subtype, BPD I patients had the highest CSF/serum albumin ratios. Moreover, BPD patients on antipsychotic treatment had higher CSF/serum albumin ratio than BPD patients on other treatments. When excluding BPD patients on antipsychotic treatment the difference in CSF/serum albumin ratio between the BPD and control groups disappeared. In conclusion, antipsychotic treatment in BPD is associated with elevated CSF/serum albumin ratio, tentatively as a sign of impaired BCB function. Whether this elevation is caused by antipsychotic treatment or is associated with a certain subtype of BPD, requiring antipsychotic treatment, remains to be determined. PMID:24745469

Zetterberg, Henrik; Jakobsson, Joel; Redsäter, Mikael; Andreasson, Ulf; Pålsson, Erik; Ekman, Carl Johan; Sellgren, Carl; Johansson, Anette Gm; Blennow, Kaj; Landén, Mikael

2014-07-30

136

Clonotypic analysis of cerebrospinal fluid T cells during disease exacerbation and remission in a patient with multiple sclerosis  

Microsoft Academic Search

Migration of autoreactive T cells into the central nervous system (CNS) compartment is thought to be an important step in the pathogenesis of multiple sclerosis (MS). To follow the evolution of T cell repertoire in the CNS of a patient with relapsing–remitting MS, we analyzed cerebrospinal fluid (CSF) cells obtained during an acute clinical exacerbation, and subsequent disease remission after

Paolo A. Muraro; Riccardo Cassiani-Ingoni; Katherine Chung; Amy N. Packer; Mireia Sospedra; Roland Martin

2006-01-01

137

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

Microsoft Academic Search

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

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

138

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

Microsoft Academic Search

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

Darko Oreškovi?; Marijan Klarica; Miroslav Vuki?

2002-01-01

139

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

Microsoft Academic Search

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

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

2009-01-01

140

Plasma and cerebrospinal fluid probenecid concentrations as related to accumulation of acidic biogenic amine metabolites in man  

Microsoft Academic Search

The oral administration of probenecid (100 mg\\/kg\\/18 h) to depressed patients results in marked increases in the acidic metabolites of biogenic amines in the cerebrospinal fluid (CSF). In contrast to previous reports (where lower dose rates of probenecid were employed) the increases in 5-hydroxyindoleacetic acid and homovanillic acid were independent of plasma or CSF probenecid concentrations. Higher plasma and CSF

James M. Perel; Morton Levitt; David L. Dunner

1974-01-01

141

Adenosine deaminase activity in cerebrospinal fluid of HIV-infected patients: limited value for diagnosis of tuberculous meningitis  

Microsoft Academic Search

Adenosine deaminase activity (ADA) determination in cerebrospinal fluid (CSF) is considered a specific test for the diagnosis of tuberculous meningitis. In order to study the variability of this marker in patients with different neurological disorders associated with HIV infection, and its utility for the diagnosis of tuberculous meningitis in these patients, the ADA levels in 417 CSF samples from HIV-infected

I. Corral; C. Quereda; E. Navas; P. Martín-Dávila; M.-J. Pérez-Elías; J.-L. Casado; V. Pintado; J. Cobo; E. Pallarés; J. Rubí; S. Moreno

2004-01-01

142

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

PubMed Central

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

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

143

Cerebrospinal fluid (1,3)-?-D-glucan detection as an aid for diagnosis of iatrogenic fungal meningitis.  

PubMed

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

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; Zhang, Sean X

2013-04-01

144

The value of the measurement of cerebrospinal fluid levels of lysozyme in the diagnosis of neurological disease  

Microsoft Academic Search

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

G Firth; J Rees; R O McKeran

1985-01-01

145

Triosephosphate Isomerase and Glyceraldehyde3Phosphate Dehydrogenase-Reactive Autoantibodies in the Cerebrospinal Fluid of Patients with Multiple Sclerosis1  

Microsoft Academic Search

Our previous results revealed that Igs in lesions and single chain variable fragment Abs (scFv-Abs) generated from clonal B cells in the cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS) bind to axons in MS brains. To study the axonal Ags involved in MS, we identified the glycolytic enzymes, triosephosphate isomerase (TPI) and GAPDH, using Igs from the CSF

Johanna Kolln; Hui-Min Ren; Reng-Rong Da; Yiping Zhang; Edzard Spillner; Michael Olek; Neal Hermanowicz; Lutz G. Hilgenberg; Martin A. Smith; Stanley van den Noort; Yufen Qin

146

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

Microsoft Academic Search

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

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

1994-01-01

147

Jacalin-unbound fraction of Taenia saginata in immunodiagnosis of neurocysticercosis in human cerebrospinal fluid.  

PubMed

The aim of this study was to evaluate jacalin-bound fraction (JBF) and jacalin-unbound fraction (JUF) of the total saline extract from Taenia saginata metacestodes for human neurocysticercosis (NC) immunodiagnosis in cerebrospinal fluid. Total extract, JBF, and JUF were separated by affinity chromatography using Sepharose(®)-jacalin and were tested in enzyme-linked immunosorbent assay (ELISA) and Western blotting (WB) to detect immunoglobulin G. In ELISA test, JUF showed the higher diagnostic efficiency and specificity indexes, 92% and 100%, respectively. In WB, 5 immunodominant proteins (39-42, 47-52, 64-68, 70, and 75 kDa) were detected when using JUF. In conclusion, the results achieved demonstrate that JUF, obtained from T. saginata metacestodes, are an important source of specific peptides and are efficient in the diagnosis of NC. PMID:20846809

da Silva Nunes, Daniela; da Silva Ribeiro, Vanessa; Manhani, Marianna Nascimento; Costa-Cruz, Julia Maria

2010-11-01

148

Detection of immunoglobulin M in cerebrospinal fluid from syphilis patients by enzyme-linked immunosorbent assay.  

PubMed Central

Cerebrospinal fluid (CSF) samples were evaluated in an immunoglobulin M enzyme-linked immunosorbent assay (IgM ELISA) for syphilis with sonic extracts of Treponema pallidum coated on polystyrene plates. The ELISA procedure was reproducible, and T. pallidum antigens were stable., A total of 15 CSF samples from patients with neurosyphilis, 18 CSF samples from patients with syphilis, 12 CSF samples from patients treated for syphilis, and 494 CSF samples from patients with neurologic or other systemic diseases were tested. The IgM ELISA gave reactive results in all of six symptomatic and congenital neurosyphilitic patients and none of nine asymptomatic neurosyphilitic patients. Of 524 CSF samples from nonneurosyphilitic individuals, 513 were nonreactive, resulting in 98% test specificity. The IgM ELISA in CSF should prove to be useful for confirmation of symptomatic neurosyphilis. PMID:3533984

Lee, J B; Farshy, C E; Hunter, E F; Hambie, E A; Wobig, G H; Larsen, S A

1986-01-01

149

Penicillin concentrations in cerebrospinal fluid after different treatment regimens for syphilis.  

PubMed Central

The concentrations of penicillin in the cerebrospinal fluid (CSF) were compared simultaneously with those in the serum in 17 patients with syphilis. The antibiotic concentrations were measured by the agar well diffusion method. There were no detectable concentrations of penicillin in the CSF after administration of benzathine penicillin 2.4 megaunits, benzathine penicillin 7.2 megaunits, procaine penicillin in aluminium monostearate (PAM) 12 megaunits, or aqueous procaine penicillin G 2.4 megaunits. Only after high doses of aqueous penicillin G 24 megaunits daily or aqueous penicillin G 2 megaunits daily together with oral probenecid 2 g daily was penicillin detectable in the CSF. The concentrations after the latter regimen were the highest and much higher than the minimum inhibitory concentration for Treponema pallidum. PMID:7448578

Polnikorn, N; Witoonpanich, R; Vorachit, M; Vejjajiva, S; Vejjajiva, A

1980-01-01

150

[Endoscopic treatment of idiopathic spontaneous although cerebrospinal fluid rhinorrhea: a case report].  

PubMed

Although cerebrospinal fluid (CSF) rhinorrhea is a rarely seen clinical entity, it is a condition which should be considered carefully by otolaryngologists and neurosurgeons because it has the possibility of serious complications unless it is treated. Trauma is the most common causative factor. Idiopathic spontaneous CSF rhinorrhea is a very rare entity which is difficult to manage and which has high recurrence rates. Although in the past CSF rhinorrhea used to be treated by intracranial route, nowadays endonasal endoscopic surgery is preferred because of wide usage of rigid endoscopes with much fewer complications, In this article, a case of 43-year-old female with idiopathic spontaneous CSF rhinorrhea repaired by endonasal endoscopic surgery is presented, and the diagnosis and the treatment of CSF rhinorrhea is reviewed. PMID:19793046

Kansu, Leyla; Akkuzu, Babür; Avci, Suat

2009-01-01

151

Repair of Spontaneous Cerebrospinal Fluid Otorrhea from Defect of Middle Cranial Fossa  

PubMed Central

Spontaneous cerebrospinal fluid (CSF) otorrhea is defined as CSF otorrhea where there are no identifiable causes including previous trauma, surgery, infection, neoplasm or congenital anomaly. The condition is rare. The origin of CSF leak is commonly a defect in the tegmen of the middle cranial fossa. The pathophysiology of spontaneous CSF otorrhea is unclear. Two theories of the etiology of bony defects of the temporal bone are the congenital bony defect theory and arachnoid granulation theory. The authors experienced a case of a 49-year-old female patient admitted with the complaint of persistent right ear fullness. Computed tomography revealed a large defect of the middle fossa and suspicious CSF otorrhea through the defect of tegmen tympani. Repair was successful with multiple bone chips using the transmastoid approach. The postoperative course was good and there has been no recurrence of the CSF leakage. PMID:24653924

Goh, Young Bum; Han, Chi-Sung

2013-01-01

152

Measurement of cytokine levels in cerebrospinal fluid over time in neonatal Enterococcal meningitis.  

PubMed

Enterococcus faecalis is rarely involved in neonatal meningitis. Several studies have indicated that the cytokines related to bacterial infection may induce nerve cell damage; therefore, the cytokine levels in cerebrospinal fluid (CSF) could represent a valuable hallmark for rapid recognition of the disease and evaluation of the degree of neurological involvement. We analyzed cytokine levels in the CSF of a neonate with E. faecalis meningitis over time. Tumor necrosis factor-? (TNF-?) tended to be elevated during the acute phase of infection, and then decreased during the convalescent stage after treatment. CSF inflammatory cytokine measurement may provide important clues for predicting the development of complications in the host because some of these cytokines, such as TNF-?, can injure neurons. PMID:25252071

Ikeda, Naho; Suganuma, Hiroki; Ohkawa, Natsuki; Nagata, Satoru; Shoji, Hiromichi; Shimizu, Toshiaki

2014-08-01

153

Plasma and cerebrospinal fluid concentrations of paracetamol after a single intravenous dose of propacetamol.  

PubMed Central

Since the antipyretic and probably the analgesic effects of paracetamol are, at least in part, centrally mediated, its plasma and cerebrospinal fluid (CSF) concentrations were measured in 43 patients with nerve-root compression pain. Each subject was given a short i.v. infusion of 2 g propacetamol, a prodrug which is hydrolysed to paracetamol within 7 min. Single blood and CSF samples were drawn concomitantly in each patient at intervals between 20 min and 12 h. Maximum CSF drug concentrations were observed at the 4th hour, subsequent concentrations exceeding those in plasma. The elimination half-life of paracetamol calculated from pooled data was shorter in plasma (2.4 h) than in CSF (3.2 h). The time-course of paracetamol in CSF may parallel that of analgesic effect. PMID:1633071

Bannwarth, B; Netter, P; Lapicque, F; Gillet, P; Péré, P; Boccard, E; Royer, R J; Gaucher, A

1992-01-01

154

The cerebrospinal fluid provides a proliferative niche for neural progenitor cells  

PubMed Central

Cortical development depends on the active integration of cell autonomous and extrinsic cues, but the coordination of these processes is poorly understood. Here, we show that the apical complex protein Pals1 and Pten have opposing roles in localizing the Igf1R to the apical, ventricular domain of cerebral cortical progenitor cells. We found that the cerebrospinal fluid (CSF), which contacts this apical domain, has an age-dependent effect on proliferation, much of which is attributable to Igf2, but that CSF contains other signaling activities as well. CSF samples from patients with glioblastoma multiforme show elevated Igf2 and stimulate stem cell proliferation in an Igf2-dependent manner. Together, our findings demonstrate that the apical complex couples intrinsic and extrinsic signaling, enabling progenitors to sense and respond appropriately to diffusible CSF-borne signals distributed widely throughout the brain. The temporal control of CSF composition may have critical relevance to normal development and neuropathological conditions. PMID:21382550

Lehtinen, Maria K.; Zappaterra, Mauro W.; Chen, Xi; Yang, Yawei J.; Hill, Anthony; Lun, Melody; Maynard, Thomas; Gonzalez, Dilenny; Kim, Seonhee; Ye, Ping; D’Ercole, A. Joseph; Wong, Eric T.; LaMantia, Anthony S.; Walsh, Christopher A.

2011-01-01

155

Identification of biomarkers in cerebrospinal fluid and serum of multiple sclerosis patients by immunoproteomics approach.  

PubMed

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

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

2014-01-01

156

Cerebrospinal fluid penetration of active metabolites of cyclophosphamide and ifosfamide in rhesus monkeys.  

PubMed

The penetration of the active metabolites of cyclophosphamide (CP) and ifosfamide (IF) into cerebrospinal fluid (CSF) was determined in rhesus monkeys following an i.v. infusion of 1 gm/m2 of CP and IF. Active metabolites were measured using a high-performance liquid chromatography assay with fluorometric detection following derivatization with m-aminophenol. CSF to blood ratios of the active metabolites of CP and IF were found to be 0.17 and 0.13 following systemic dosing of CP and IF, respectively. The levels achieved in the CSF, however, were equivalent to levels known to be cytocidal to malignant cell lines derived from tumors which metastasize to the central nervous system. Only one animal demonstrated neurotoxicity with IF. CSF levels of active metabolite in this animal were similar to those observed in the other animals. PMID:3349482

Arndt, C A; Balis, F M; McCully, C L; Colvin, O M; Poplack, D G

1988-04-15

157

Cerebrospinal fluid constituents of cat vary with susceptibility to motion sickness  

NASA Technical Reports Server (NTRS)

The cerebrospinal fluid drawn from the fourth ventricles of the brains of cats during and after the development of motion sickness was studied to determine what neurotransmitters may be involved in the development of the sickness. The analytical procedure, which uses HPLC coupled with n-electrode coulometric electrochemical detection to measure many compounds with picogram sensitivity, is described. Baseline levels of DOPAC, MHPGSO4, uric acid, DA, 5-HIAA, and HVA were lower on motion and control days in cats which became motion sick when compared with cats which did not. None of the total of 36 identified compounds identified in the samples varied as a function of either exposure to motion or provocation of emesis. It is concluded that susceptibility to motion sickness is a manifestation of individual differences related to fundamental neurochemical composition.

Lucot, James B.; Crampton, George H.; Matson, Wayne R.; Gamache, Paul H.

1989-01-01

158

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

PubMed Central

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

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

159

Septal cartilage plug technique in spontaneous cerebrospinal fluid rhinorrhea postoperatively diagnosed with partial empty sella syndrome.  

PubMed

The otolaryngologist should consider empty sella syndrome for diagnostic guidance when evaluating patients with nontraumatic spontaneous cerebrospinal fluid (CSF) rhinorrhea. The radiographic finding of empty sella is frequently reported in patients with benign intracranial hypertension (BIH). Patients who have a spontaneous CSF leak in the absence of florid symptoms of BIH may have a disrupted pattern of CSF flow, and because they are actively leaking CSF before surgical repair, they may be at risk for developing elevated intracranial pressure and BIH after the CSF leaks have been successfully closed. We describe a patient with CSF rhinorrhea who developed headache, papilledema, and visual disturbance after surgical repair of the CSF leak. The leak was repaired by the placement of a septal cartilage plug with a free mucosal suture graft. This technique provides fundamental biomechanical stability, reduces the complexity of the multilayer packing method, and promotes an effective seal. PMID:24911604

Chang, Chul

2014-07-01

160

Resistance to outflow of cerebrospinal fluid after central infusions of angiotensin  

NASA Technical Reports Server (NTRS)

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.

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

1992-01-01

161

Cerebrospinal fluid biomarkers of Alzheimer’s disease in cognitively healthy elderly  

PubMed Central

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 (Aß42), 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

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

2014-01-01

162

Mass spectral measurements of the apoHDL in horse (Equus caballus) cerebrospinal fluid.  

PubMed

As a continuation of our proteogenomic studies of equine apolipoproteins, we have obtained molecular masses for several of the apolipoproteins associated with the HDL in horse cerebrospinal fluid (CSF). Using electrospray-ionization mass spectrometry (ESI-MS), we report on values for apolipoproteins, A-I and A-II, as well as acylated apoA-I. In comparison with our previously published data on equine plasma apolipoproteins, there appears to be a higher percentage of acylated apoA-I in the CSF than in plasma. As was the case in plasma, apoA-II circulates as a homodimer. These studies also revealed a protein with a mass of 34,468Da that we are speculating is the value for horse apoE. PMID:22377539

Puppione, Donald L; Della Donna, Lorenza; Bassilian, Sara; Souda, Puneet; MacDonald, Melinda H; Whitelegge, Julian P

2012-06-01

163

A Window into the Heterogeneity of Human Cerebrospinal Fluid A? Peptides  

PubMed Central

The initiating event in Alzheimer's disease (AD) is an imbalance in the production and clearance of amyloid beta (A?) peptides leading to the formation of neurotoxic brain A? assemblies. Cerebrospinal Fluid (CSF), which is a continuum of the brain, is an obvious source of markers reflecting central neuropathologic features of brain diseases. In this review, we provide an overview and update on our current understanding of the pathobiology of human CSF A? peptides. Specifically, we focused our attention on the heterogeneity of the CSF A? world discussing (1) basic research studies and what has been translated to clinical practice, (2) monomers and other soluble circulating A? assemblies, and (3) communication modes for A? peptides and their microenvironment targets. Finally, we suggest that A? peptides as well as other key signals in the central nervous system (CNS), mainly involved in learning and hence plasticity, may have a double-edged sword action on neuron survival and function. PMID:21876644

Ghidoni, Roberta; Paterlini, Anna; Albertini, Valentina; Stoppani, Elena; Binetti, Giuliano; Fuxe, Kjell; Benussi, Luisa; Agnati, Luigi F.

2011-01-01

164

Cerebrospinal fluid homovanillic acid levels in rapid-onset dystonia-parkinsonism.  

PubMed

Rapid-onset dystonia-parkinsonism (RDP) is characterized by sudden onset over hours to days of dystonia, dysphagia, dysarthria, and parkinsonism. RDP has been reported by our group in two apparently unrelated families. We now report analysis of cerebrospinal fluid metabolites of dopamine, norepinephrine, and serotonin for mild and severely affected individuals, known asymptomatic gene carriers, and at-risk individuals from both families with RDP. Levels of the dopamine metabolite homovanillic acid (HVA) were decreased in severely affected patients and in some asymptomatic gene carriers. HVA levels increased with treatment in some affected individuals, but this increase did not predict clinical response to carbidopa/levodopa. We suggest that a low HVA level is a biological marker with modest association to the diagnosis of RDP. PMID:9546335

Brashear, A; Butler, I J; Hyland, K; Farlow, M R; Dobyns, W B

1998-04-01

165

The Choroid Plexus and Cerebrospinal Fluid: Emerging Roles in Development, Disease, and Therapy  

PubMed Central

Although universally recognized as the source of cerebrospinal fluid (CSF), the choroid plexus (ChP) has been one of the most understudied tissues in neuroscience. The reasons for this are multiple and varied, including historical perceptions about passive and permissive roles for the ChP, experimental issues, and lack of clinical salience. However, recent work on the ChP and instructive signals in the CSF have sparked new hypotheses about how the ChP and CSF provide unexpected means for regulating nervous system structure and function in health and disease, as well as new ChP-based therapeutic approaches using pluripotent stem cell technology. This minisymposium combines new and established investigators to capture some of the newfound excitement surrounding the ChP-CSF system. PMID:24198345

Bjornsson, Christopher S.; Dymecki, Susan M.; Gilbertson, Richard J.; Holtzman, David M.

2013-01-01

166

Cerebrospinal fluid can be used for HIV genotyping when it fails in blood  

PubMed Central

Blood plasma specimens are the clinical standard for HIV-1 pol gene genotyping from viral populations; however, it is not always successful, often from low viral loads or the presence of polymerase chain reaction (PCR) inhibitors. Objective To describe the successful of HIV-1 genotyping in two samples of cerebrospinal fluid (CSF), after genotype procedures failed from blood. Method Two HIV-infected patients enrolled in a neurocognitive research study were evaluated when standard HIV-1 genotyping failed from blood plasma samples. Genotyping was performed using the commercial system TRUGENE® HIV-1 Genotyping Kit and the OpenGene® DNA Sequencing System (Siemens Healthcare Diagnostics, Tarrytown, NY, USA). Results CSF genotyping was performed via the same commercial platform and was successful in both cases. Conclusion This report demonstrates that CSF could be used as an alternate clinical specimen for HIV-1 genotyping when it fails from blood. PMID:25054982

Rotta, Indianara; Raboni, Sonia Mara; Ribeiro, Cléa Elisa Lopes; Riedel, Maristela; Winhescki, Maria da Graça; Smith, Davey M.; Ellis, Ronald J.; de Almeida, Sérgio Monteiro

2014-01-01

167

Normal pressure hydrocephalus. Influences on cerebral hemodynamic and cerebrospinal fluid pressure--chemical autoregulation  

SciTech Connect

Blood flow in the cerebral gray matter was measured in normal pressure hydrocephalus and Alzheimer disease by 133Xe inhalation. Flow values in the frontal and temporal gray matter increased after lowering cerebrospinal fluid (CSF) pressure by lumbar puncture in normal pressure hydrocephalus (p less than 0.05) and also after shunting. One case with cerebral complications did not improve clinically. In Alzheimer disease the reverse (decreases in flow in the gray matter) occurred after removal of CSF. Normal pressure hydrocephalus was associated with impaired cerebral vasomotor responsiveness during 100% oxygen and 5% carbon dioxide inhalation. This complication was restored toward normal after CSF removal and/or shunting. Cerebral blood flow measurements appear to be useful for confirming the diagnosis of normal pressure hydrocephalus and predicting the clinical benefit from shunting.

Meyer, J.S.; Tachibana, H.; Hardenberg, J.P.; Dowell, R.E. Jr.; Kitagawa, Y.; Mortel, K.F.

1984-02-01

168

"Tear drops" in the cerebrospinal fluid: correct by scatter, but pathognomonic by site.  

PubMed

Extramedullary relapse in acute promyelocytic leukemia (APL) is rare, but occurs most commonly in central nervous system (CNS), generally in high-risk cases (total leucocyte count ?10,000/µL, atypical morphology or disseminated intravascular coagulation at presentation), and concomitant with bone marrow (BM) relapse. Here we describe a case of APL who except for CD56 positivity was low-risk, but had a CNS relapse without concomitant BM involvement. Diagnosis of isolated CNS relapse was based on characteristic tear-drop pattern for CD45/side scatter plot on flow cytometry, a full compatible immunophenotype and cytomorphology in the cerebrospinal fluid. The case illustrates the value of the latter and the importance of including CD56 in risk assessment of APL. © 2014 Clinical Cytometry Society. PMID:25220629

Mittal, Reena; Chopra, Anita; Soni, Sushant; Bakhshi, Sameer; Kumar, Rajive

2014-09-12

169

Alterations in Protein Regulators of Neurodevelopment in the Cerebrospinal Fluid of Infants with Posthemorrhagic Hydrocephalus of Prematurity*  

PubMed Central

Neurological outcomes of preterm infants with posthemorrhagic hydrocephalus are among the worst in newborn medicine. There remains no consensus regarding the diagnosis or treatment of posthemorrhagic hydrocephalus, and the pathological pathways leading to the adverse neurological sequelae are poorly understood. In the current study, we developed an innovative approach to simultaneously identify potential diagnostic markers of posthemorrhagic hydrocephalus and investigate novel pathways of posthemorrhagic hydrocephalus-related neurological disability. Tandem multi-affinity fractionation for specific removal of plasma proteins from the hemorrhagic cerebrospinal fluid samples was combined with high resolution label-free quantitative proteomics. Analysis of cerebrospinal fluid obtained from infants with posthemorrhagic hydrocephalus demonstrated marked differences in the levels of 438 proteins when compared with cerebrospinal fluid from age-matched control infants. Amyloid precursor protein, neural cell adhesion molecule-L1, neural cell adhesion molecule-1, brevican and other proteins with important roles in neurodevelopment showed profound elevations in posthemorrhagic hydrocephalus cerebrospinal fluid compared with control. Initiation of neurosurgical treatment of posthemorrhagic hydrocephalus resulted in resolution of these elevations. The results from this foundational study demonstrate the significant promise of tandem multi-affinity fractionation-proteomics in the identification and quantitation of protein mediators of neurodevelopment and neurological injury. More specifically, our results suggest that cerebrospinal fluid levels of proteins such as amyloid precursor protein or neural cell adhesion molecule-L1 should be investigated as potential diagnostic markers of posthemorrhagic hydrocephalus. Notably, dysregulation of the levels these and other proteins may directly affect ongoing neurodevelopmental processes in these preterm infants, providing an entirely new hypothesis for the developmental disability associated with posthemorrhagic hydrocephalus. PMID:22186713

Morales, Diego M.; Townsend, R. Reid; Malone, James P.; Ewersmann, Carissa A.; Macy, Elizabeth M.; Inder, Terrie E.; Limbrick, David D.

2012-01-01

170

Pseudocholinesterase activity in cerebrospinal fluid as a biomarker of solid central nervous system tumors in children  

PubMed Central

Aim To determine the activity of pseudocholinesterase (PChE) in cerebrospinal fluid (CSF) and serum in children with solid central nervous system (CNS) tumor and to assess whether PChE activity could be a valid biomarker for solid CNS tumors in children. Methods The study and control group included 30 children each. Children in the study group had a solid CNS tumor, while those from the control group had never suffered from any tumor diseases. CSF and serum samples were collected from all participants and PChE activity was determined using the Ellman’s spectrophotometric method. PChE activity in CSF was shown as a cerebrospinal fluid/serum ratio expressed in percentage, ie, PChE CSF/serum ratio. Receiver operating characteristic (ROC) curve was used to assess whether PChE activity can be used as a biomarker for identifying children with solid CNS tumors. Results Children with solid CNS tumor had significantly higher PChE activity in CSF and serum, as well as PChE CSF/serum ratio (P?=?0.001). PChE CSF/serum ratio in the study group was 2.38% (interquartile range [IQR] 1.14-3.97) and 1.09% (IQR 0.95-1.45) in the control group. ROC curve analysis of PChE CSF/serum ratio resulted in an area under the curve (AUC) value of 0.76 (95% confidence interval [CI] 0.63-0.88) and a cut-off of 1.09. Twenty five of 29 patients with elevated PChE CSF/serum ratio had a tumor, corresponding to a sensitivity of 83% and a specificity of 53%. Conclusion PChE CSF/serum ratio may be used as a test or biomarker with good sensitivity for solid CNS tumors in children. PMID:24170721

Mikecin, Lili; Križmari?, Miljenko; Stepan Giljevi?, Jasminka; Gjurašin, Miroslav; Kern, Josipa; Leni?ek Krleža, Jasna; Popovi?, Ljiljana

2013-01-01

171

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

NASA Astrophysics Data System (ADS)

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.

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

2012-06-01

172

Alterations in cerebrospinal fluid glycerophospholipids and phospholipase A2 activity in Alzheimer's disease[S  

PubMed Central

Our aim is to study selected cerebrospinal fluid (CSF) glycerophospholipids (GP) that are important in brain pathophysiology. We recruited cognitively healthy (CH), minimally cognitively impaired (MCI), and late onset Alzheimer's disease (LOAD) study participants and collected their CSF. After fractionation into nanometer particles (NP) and supernatant fluids (SF), we studied the lipid composition of these compartments. LC-MS/MS studies reveal that both CSF fractions from CH subjects have N-acyl phosphatidylethanolamine, 1-radyl-2-acyl-sn-glycerophosphoethanolamine (PE), 1-radyl-2-acyl-sn-glycerophosphocholine (PC), 1,2-diacyl-sn-glycerophosphoserine (PS), platelet-activating factor-like lipids, and lysophosphatidylcholine (LPC). In the NP fraction, GPs are enriched with a mixture of saturated, monounsaturated, and polyunsaturated fatty acid species, while PE and PS in the SF fractions are enriched with PUFA-containing molecular species. PC, PE, and PS levels in CSF fractions decrease progressively in participants from CH to MCI, and then to LOAD. Whereas most PC species decrease equally in LOAD, plasmalogen species account for most of the decrease in PE. A significant increase in the LPC-to-PC ratio and PLA2 activity accompanies the GP decrease in LOAD. These studies reveal that CSF supernatant fluid and nanometer particles have different GP composition, and that PLA2 activity accounts for altered GPs in these fractions as neurodegeneration progresses. PMID:23868911

Fonteh, Alfred N.; Chiang, Jiarong; Cipolla, Matthew; Hale, Jack; Diallo, Fatimatou; Chirino, Alejandra; Arakaki, Xianghong; Harrington, Michael G.

2013-01-01

173

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

PubMed

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

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

174

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

PubMed Central

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

David, Monique Antoinette; Tayebi, Mourad

2014-01-01

175

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

PubMed

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

Oreškovi?, D; Klarica, M

2011-08-01

176

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

PubMed

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

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

2014-05-01

177

Cerebrospinal fluid flow impedance is elevated in Type I Chiari malformation.  

PubMed

Diagnosis of Type I Chiari malformation (CMI) is difficult because the most commonly used diagnostic criterion, cerebellar tonsillar herniation (CTH) greater than 3-5?mm past the foramen magnum, has been found to have little correlation with patient symptom severity. Thus, there is a need to identify new objective measurement(s) to help quantify CMI severity. This study investigated longitudinal impedance (LI) as a parameter to assess CMI in terms of impedance to cerebrospinal fluid motion near the craniovertebral junction. LI was assessed in CMI patients (N?=?15) and age-matched healthy controls (N?=?8) using computational fluid dynamics based on subject-specific magnetic resonance imaging (MRI) measurements of the cervical spinal subarachnoid space. In addition, CTH was measured for each subject. Mean LI in the CMI group (551?±?66?dyn/cm5) was significantly higher than in controls (220?±?17?dyn/cm5, p < 0.001). Mean CTH in the CMI group was 9.0?±?1.1?mm compared to -0.4?±?0.5?mm in controls. Regression analysis of LI versus CTH found a weak relationship (R2?=?0.46, p < 0.001), demonstrating that CTH was not a good indicator of the impedance to CSF motion caused by cerebellar herniation. These results showed that CSF flow impedance was elevated in CMI patients and that LI provides different information than a standard CTH measurement. Further research is necessary to determine if LI can be useful in CMI patient diagnosis. PMID:24362680

Shaffer, Nicholas; Martin, Bryn A; Rocque, Brandon; Madura, Casey; Wieben, Oliver; Iskandar, Bermans J; Dombrowski, Stephen; Luciano, Mark; Oshinski, John N; Loth, Francis

2014-02-01

178

Vitamin D-binding protein in cerebrospinal fluid is associated with multiple sclerosis progression.  

PubMed

Multiple sclerosis is a neurological disorder that presents with symptoms including inflammation, neurodegeneration, and demyelination of the central nervous system (CNS). Secondary progressive multiple sclerosis (SPMS) manifests with serious physical disability. To quantitatively analyze differential protein expression in patients with SPMS, we performed two-dimensional fluorescence difference in-gel electrophoresis, followed by mass spectrometry on the cerebrospinal fluid of these patients and patients with other neurological diseases. Vitamin D-binding protein (DBP), gelsolin, albumin, etc. showed more than a 1.5-fold difference between the two groups. Based on these results, an experimental allergic encephalomyelitis (EAE) model of multiple sclerosis in Lewis rats was used to investigate DBP's role in the disease. Protein levels, mRNA transcripts, and ligands of DBP in different regions of the CNS were evaluated under various vitamin D intake levels. Here, DBP levels increased in the experimental rat groups compared to the control groups regardless of vitamin D intake. Moreover, DBP mRNA levels varied in different parts of the CNS including spinal cords in the experimental groups. The observed differences between DBP protein and mRNA levels in the experimental groups' spinal cords could be derived from the disruption of the blood-brain barrier. Furthermore, an interaction between DBP and actin was confirmed using coimmunoprecipitation and western blot. These results indicate a role for DBP in the actin scavenge system. Moreover, in the experimental group that received oral vitamin D3 supplement, we observed both delayed onset and diminished severity of the disease. When DBP was upregulated, however, the benefits from the vitamin D3 supplements were lost. Thus, we inferred that high levels of DBP were adverse to recovery. In conclusion, here we observed upregulated DBP in the cerebrospinal fluid could serve as a specific diagnostic biomarker for the progression of multiple sclerosis. Next, we demonstrate the vital function of increased levels of free vitamin D metabolites for multiple sclerosis treatment. Finally, vitamin D supplements may be particularly beneficial for SPMS patients. PMID:23339019

Yang, Mingchong; Qin, Zhaoyu; Zhu, Yanyan; Li, Yun; Qin, Yanjiang; Jing, Yongsheng; Liu, Shilian

2013-06-01

179

A more efficient enzyme-linked immunosorbent assay for measurement of alpha-synuclein in cerebrospinal fluid.  

PubMed

We describe a modification of a previously described assay for the quantification of alpha-synuclein in naive cerebrospinal fluid, which allows for a more efficient quantification of alpha-synuclein. Detection limit of the assay is 3.8 ng/ml and the assay is linear until 300 ng/ml. Inter-assay and intra-assay coefficients of variation are below 15% in a wide range of concentrations. Mean recovery of the assay is 94%. The 95% upper limit of the reference range (p95) in a group of neurological controls above the age of 45 years is 62 ng/ml. This assay can be routinely applied for quantification of alpha-synuclein in cerebrospinal fluid, but not in serum, and this may serve as a possible biomarker for alpha-synucleinopathies such as Parkinson's disease and multiple system atrophy. PMID:17976734

van Geel, Wieneke J A; Abdo, W Farid; Melis, René; Williams, Sonja; Bloem, Bastiaan R; Verbeek, Marcel M

2008-02-15

180

No correlation between serotonin and its metabolite 5-HIAA in the cerebrospinal fluid and [(11) C]AZ10419369 binding measured with PET in healthy volunteers.  

PubMed

[(11) C]AZ10419369 is sensitive to pharmacologically enhanced endogenous serotonin levels. Twelve healthy volunteers underwent [(11) C]AZ10419369 PET and lumbar puncture. There were no correlations between [(11) C]AZ10419369 binding and concentrations of serotonin and its metabolite 5-HIAA in cerebrospinal fluid, suggesting that [(11) C]AZ10419369 brain binding does not reflect baseline serotonin levels in cerebrospinal fluid. PMID:24988901

Tiger, Mikael; Svenningsson, Per; Nord, Magdalena; Jabre, Sandra; Halldin, Christer; Lundberg, Johan

2014-10-01

181

Clinical Evaluation of the Gen-Probe Amplified Direct Test for Detection of Mycobacterium tuberculosis Complex Organisms in Cerebrospinal Fluid  

Microsoft Academic Search

Eighty-four cerebrospinal fluid (CSF) samples from different children who presented with signs and symp- toms of meningitis were evaluated for the presence of Mycobacterium tuberculosis complex organisms by the Gen- Probe Amplified Mycobacterium tuberculosis Direct Test (MTD; Gen-Probe, San Diego, Calif.). All CSF samples had negative acid-fast smears by the Ziehl-Neelsen staining method. M. tuberculosis was recovered from five samples.

ANNE M. LANG; JESUS FERIS-IGLESIAS; CHABELA PENA; JACQUELINE F. SANCHEZ; LESLIE STOCKMAN; PAUL RYS; GLENN D. ROBERTS; NANCY K. HENRY; DAVID H. PERSING; FRANKLIN R. COCKERILL; Robert Reid

1998-01-01

182

Cerebrospinal Fluid Monoaminergic Metabolites in Wild Papio anubis and P. hamadryas are Concordant with Taxon-specific Behavioral Ontogeny  

Microsoft Academic Search

We used a cross-sectional sample to compare ontogenetic trajectories in the concentrations of monoamine neurotransmitter metabolites\\u000a in cerebrospinal fluid of wild anubis (Papio anubis, n?=?49) and hamadryas (P. hamadryas, n?=?54) baboons to test the prediction that they would differ, especially in males, in association with their distinct behavioral\\u000a ontogenies. Values of all 3 metabolites [3-methoxy-4-hydroxyphenylglycol (MHPG), the norepinephrine metabolite; 5-hydroxyindoleacetic

Clifford J. Jolly; Jane E. Phillips-Conroy; Jay R. Kaplan; J. John Mann

2008-01-01

183

Monoamine metabolism in the cerebrospinal fluid in Parkinson's disease: relationship to clinical symptoms and subsequent therapeutic outcomes  

Microsoft Academic Search

Summary  We correlated monoamine concentrations in the cerebrospinal fluid from de novo (untreated) patients with Parkinson's disease with their clinical symptoms and therapeutic outcome after two years of L-dopa with\\/without other anti-parkinson medication. A significant correlation was found between the severity of some parkinsonian symptoms and the reduction in particular monoamines: Hoehn and Yahr's stage with dopamine, norepinephrine, and homovanillic acid:

H. Tohgi; T. Abe; S. Takahashi; J. Takahashi; Y. Nozaki; M. Ueno; T. Kikuchi

1993-01-01

184

Free d -amino acids in human cerebrospinal fluid of alzheimer disease, multiple sclerosis, and healthy control subjects  

Microsoft Academic Search

This is the first report of the presence of freeD-amino acids in lumbar and ventricular human cerebrospinal fluid (CSF) of individuals with Alzheimer disease (AD) compared\\u000a with CSF of normal control subjects and with individuals affected by multiple sclerosis, as an unrelated neurologic disorder.\\u000a Freed-amino acids are present at significantly higher levels in AD CSF than normal CSF, whereas in

George H. Fisher; Leonard Petrucelli; Christina Gardner; Carolyn Emory; William H. Frey; Luigi Amaducci; Sandro Sorbi; Giovanna Sorrentino; Mauro Borghi; Antimo D'aniello

1994-01-01

185

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

Microsoft Academic Search

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

Malcolm B. Bowers

1972-01-01

186

Modification of a method for cannulation of the cisterna magna in sheep to enable chronic collection of cerebrospinal fluid.  

PubMed

A method is described for chronic cannulation of the cisterna magna to enable repeated sampling of cerebrospinal fluid from conscious, ambulatory sheep by means of a flexible vinyl tube. Ease of sampling and duration of cannula patency are similar to those obtained with rigid, metal cannulae, but this modified method minimizes the degree of surgical intervention, and possible trauma, occurring during placement of the cannula. PMID:25331630

Wilson, Mo; Barrell, Gk

2015-01-01

187

Simultaneous determination of nikethamide and lidocaine in human blood and cerebrospinal fluid by high performance liquid chromatography  

Microsoft Academic Search

Nikethamide and lidocaine are often requested to be quantified simultaneously in forensic toxicological analysis. A simple reversed-phase high performance liquid chromatography (RP-HPLC) method has been developed for their simultaneous determination in human blood and cerebrospinal fluid. The method involves simple protein precipitation sample treatment followed by quantification of analytes using HPLC at 263nm. Analytes were separated on a 5?m Zorbax

Lili Chen; Linchuan Liao; Zhong Zuo; Youyi Yan; Lin Yang; Qiang Fu; Yu Chen; Junhong Hou

2007-01-01

188

Degradation of myelin basic protein in myelin by protease in cerebrospinal fluid and effects of protease inhibitors  

Microsoft Academic Search

Neutral protease is shown to be present in cell-free human cerebrospinal fluid. Incubation of heated human myelin with CSF at 25°C resulted in a marked reduction of myelin basic protein (MBP) with time. Degradation products appeared at apparent mol wt 14 KDa and 12 KDa on polyacrylamide gel electrophoresis. Optimal pH of the protease was 7.0. This protease was activated

Takashi Inuzuka; Shuzo Sato; Hiroko Baba; Tadashi Miyatake

1986-01-01

189

Cerebrospinal Fluid Microglial Markers in Alzheimer’s Disease: Elevated Chitotriosidase Activity but Lack of Diagnostic Utility  

Microsoft Academic Search

Activated microglial cells, which are the resident macrophages of the central nervous system, surround amyloid ?-plaques in\\u000a Alzheimer’s disease (AD) brains. Inflammation including microglial activation may contribute in AD pathogenesis, and biomarkers\\u000a for this process may thus be of value to study AD pathogenesis and might facilitate development of therapies targeting these\\u000a cells. We therefore examined cerebrospinal fluid (CSF) biomarkers

Niklas MattssonShahrzad; Shahrzad Tabatabaei; Per Johansson; Oskar Hansson; Ulf Andreasson; Jan-Eric Månsson; Jan-Ove Johansson; Bob Olsson; Anders Wallin; Johan Svensson; Kaj Blennow; Henrik Zetterberg

2011-01-01

190

Relationship of cerebrospinal fluid pressure, fungal burden and outcome in patients with cryptococcal meningitis undergoing serial lumbar punctures  

Microsoft Academic Search

OBJECTIVES: To assess impact of serial lumbar punctures on association between cerebrospinal fluid (CSF) opening pressure and prognosis in HIV-associated cryptococcal meningitis; to explore time course and relationship of opening pressure with neurological findings, CSF fungal burden, immune response, and CD4 cell count. DESIGN: Evaluation of 163 HIV-positive ART-naive patients enrolled in three trials of amphotericin B-based therapy for cryptococcal

Tihana Bicanic; Annemarie E Brouwer; Graeme Meintjes; Kevin Rebe; Direk Limmathurotsakul; Wirongrong Chierakul; Praprit Teparrakkul; Angela Loyse; Nicholas J White; Robin Wood; Shabbar Jaffar; Thomas Harrison

2009-01-01

191

Detection by polymerase chain reaction of Treponema pallidum DNA in cerebrospinal fluid from neurosyphilis patients before and after antibiotic treatment.  

PubMed Central

A polymerase chain reaction with nested primer pairs based on the DNA sequence of the 39-kDa bmp gene of Treponema pallidum subsp. pallidum is described. The method allowed the detection of purified T. pallidum DNA equivalent to the amount of DNA in a single bacterium and was specific for T. pallidum subspecies. After concentration of DNA, using diatomaceous earth, it was possible to detect about 100 treponemes in 1 ml of cerebrospinal fluid. Cerebrospinal fluid samples from a total of 29 symptomatic and asymptomatic patients with neurosyphilis were tested for the presence of treponemal DNA before and at various intervals after intravenous treatment with penicillin. Prior to the penicillin treatment, we detected T. pallidum DNA in 5 of 7 patients with acute symptomatic neurosyphilis, in none of the 4 patients with chronic symptomatic neurosyphilis tested before treatment, and in 2 of 16 patients with asymptomatic neurosyphilis. Unexpectedly, T. pallidum DNA was also often detected in cerebrospinal fluid long after intervenous treatment with penicillin, sometimes up to 3 years after therapy. Images PMID:1774324

Noordhoek, G T; Wolters, E C; de Jonge, M E; van Embden, J D

1991-01-01

192

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

PubMed

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

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

2014-12-01

193

Failure of cerebrospinal fluid homovanillic acid to predict levodopa response in Parkinson's disease  

PubMed Central

Lumbar cerebrospinal fluid homovanillic acid levels were estimated in 60 patients with Parkinsonism before and during levodopa treatment. There was a slight negative correlation between pretreatment CSF homovanillic acid levels and disability. There was no correlation between pretreatment homovanillic acid levels and clinical response to levodopa. Patients with high pretreatment levels did as well as those with depressed levels. High (normal or near normal) levels of CSF homovanillic acid in a patient with Parkinsonism do not necessarily indicate that the Parkinsonism will not respond to levodopa. These patients should receive the benefit of a trial of levodopa. There was also no correlation between homovanillic acid level during tratment and improvement. Patients with minimal increases in CSF homovanillic acid responded as well as those with greater elevations. Failure of levodopa to increase CSF homovanillic acid significantly does not indicate that the patient will not respond to levodopa and that levodopa should be discontinued. Other factors, such as vitamin B6 consumption, should be investigated. PMID:4753871

Weiner, William J.; Klawans, Harold L.

1973-01-01

194

Angiotensin-Converting Enzyme in Cerebrospinal Fluid and Risk of Brain Atrophy.  

PubMed

Background: Higher angiotensin-converting enzyme (ACE) activity might increase the risk of Alzheimer's disease by increasing blood pressure, and subsequent development of cerebral small vessel disease (CSVD). Yet, it may also decrease this risk, as it functions to degrade amyloid-?, thereby reducing brain atrophy. Objective: To examine the cross-sectional associations of serum and cerebrospinal fluid (CSF) ACE protein levels and activity with brain atrophy and CSVD in a memory clinic cohort. Methods: In 118 subjects from the memory clinic based Amsterdam Dementia Cohort (mean age 66 ± 8 years), ACE protein levels (ng/ml) and activity in CSF and serum were investigated. Poisson regression analyses were used to associate ACE measurements with rated global cortical atrophy, medial temporal lobe atrophy, lacunar infarcts, white matter hyperintensities, and microbleeds on brain MRI. Results: Higher CSF ACE activity was associated with a reduced risk of global brain atrophy. The relative risk (95% CI) of having global cortical atrophy ?2 per SD increase in CSF ACE activity was 0.67 (0.49; 0.93). ACE levels were not significantly related to measures of CSVD. Conclusions: These results show that high ACE might have protective effects on the brain. This could suggest that ACE inhibitors, which may lower CSF ACE levels, are not preferred as antihypertensive treatment in patients at risk for Alzheimer's disease. PMID:25201786

Jochemsen, Hadassa M; van der Flier, Wiesje M; Ashby, Emma L; Teunissen, Charlotte E; Jones, Ruth E; Wattjes, Mike P; Scheltens, Philip; Geerlings, Mirjam I; Kehoe, Patrick G; Muller, Majon

2014-09-01

195

Galeal Tack-Up Sutures to Prevent Subgaleal Cerebrospinal Fluid Collection  

PubMed Central

Objective Postoperative subgaleal cerebrospinal fluid (CSF) collection is considered as one of the common minor surgical complication which can lead to prolonged hospitalization. We introduce "galeal tack-up suture" to prevent postoperative subgaleal CSF collection. Methods Galeal tack-up suture consists of various surgical techniques which aim to fix galea to cranium in order to prevent CSF pooling in subgaleal space. A total of 87 patients who underwent craniotomy were divided into two groups while closing the wound : group A with galeal tack-up suture and group B with routine wound closure without galeal tack-up suture. The patients were observed for postoperative subgaleal CSF collection. Results Among 87 cranitomy cases, galeal tack-up suture was performed in 32 cases and routine wound closure was done in 55 cases. Postoperative subgaleal CSF collection occurred in 13 cases (15%) in which 12 cases occurred in group B patients and 1 case occurred in group A patients (p=0.026). Conclusion Galeal tack-up suture is an easy and effective technique in wound closure to prevent postoperative CSF collection. PMID:24294458

Choi, Won Ho; Koh, Young-Cho; Chun, Young Il; Cho, Joon; Song, Sang Woo

2013-01-01

196

Connective tissue spectrum abnormalities associated with spontaneous cerebrospinal fluid leaks: a prospective study.  

PubMed

We aimed to assess the frequency of connective tissue abnormalities among patients with cerebrospinal fluid (CSF) leaks in a prospective study using a large cohort of patients. We enrolled a consecutive group of 50 patients, referred for consultation because of CSF leak. All patients have been carefully examined for the presence of connective tissue abnormalities, and based on findings, patients underwent genetic testing. Ancillary diagnostic studies included echocardiography, eye exam, and histopathological examinations of skin and dura biopsies in selected patients. We identified nine patients with heritable connective tissue disorders, including Marfan syndrome, Ehlers-Danlos syndrome and other unclassified forms. In seven patients, spontaneous CSF leak was the first noted manifestation of the genetic disorder. We conclude that spontaneous CSF leaks are associated with a spectrum of connective tissue abnormalities and may be the first noted clinical presentation of the genetic disorder. We propose that there is a clinical basis for considering spontaneous CSF leak as a clinical manifestation of heritable connective tissue disorders, and we suggest that patients with CSF leaks should be screened for connective tissue and vascular abnormalities. PMID:22929030

Reinstein, Eyal; Pariani, Mitchel; Bannykh, Serguei; Rimoin, David L; Schievink, Wouter I

2013-04-01

197

Connective tissue spectrum abnormalities associated with spontaneous cerebrospinal fluid leaks: a prospective study  

PubMed Central

We aimed to assess the frequency of connective tissue abnormalities among patients with cerebrospinal fluid (CSF) leaks in a prospective study using a large cohort of patients. We enrolled a consecutive group of 50 patients, referred for consultation because of CSF leak. All patients have been carefully examined for the presence of connective tissue abnormalities, and based on findings, patients underwent genetic testing. Ancillary diagnostic studies included echocardiography, eye exam, and histopathological examinations of skin and dura biopsies in selected patients. We identified nine patients with heritable connective tissue disorders, including Marfan syndrome, Ehlers–Danlos syndrome and other unclassified forms. In seven patients, spontaneous CSF leak was the first noted manifestation of the genetic disorder. We conclude that spontaneous CSF leaks are associated with a spectrum of connective tissue abnormalities and may be the first noted clinical presentation of the genetic disorder. We propose that there is a clinical basis for considering spontaneous CSF leak as a clinical manifestation of heritable connective tissue disorders, and we suggest that patients with CSF leaks should be screened for connective tissue and vascular abnormalities. PMID:22929030

Reinstein, Eyal; Pariani, Mitchel; Bannykh, Serguei; Rimoin, David L; Schievink, Wouter I

2013-01-01

198

Procoagulant phospholipids and tissue factor activity in cerebrospinal fluid from patients with intracerebral haemorrhage.  

PubMed

Brain contains large amounts of tissue factor, the major initiator of the coagulation cascade. Neuronal apoptosis after intracerebral haemorrhage (ICH) leads to the shedding of procoagulant phospholipids (PPLs). The aim of this study was to investigate the generation of PPL, tissue factor activity (TFa), and D-Dimer (D-Di) in the cerebrospinal fluid (CSF) at the acute phase of ICH in comparison with other brain diseases and to examine the relationship between these factors and the outcome of ICH. CSF was collected from 112 patients within 48 hours of hospital admission. Thirty-one patients with no neurological or biochemical abnormalities were used to establish reference range in the CSF ("controls"). Thirty had suffered an ICH, and 51 other neurological diagnoses [12: ventricular drainage following brain surgery, 13: viral meningitis, 15: bacterial meningitis, and 11 a neurodegenerative disease (NDD)]. PPL was measured using a factor Xa-based coagulation assay and TFa by one home test. PPL, D-Di, and TFa were significantly higher (P < 0.001) in the CSF of patients with ICH than in controls. TFa levels were significantly (P < 0.05) higher in ICH than in patients with meningitides or NDD. Higher levels (P < 0.05) of TFa were observed in patients with ICH who died than in survivors. TFa measurement in the CSF of patients with ICH could constitute a new prognostic marker. PMID:24696689

Van Dreden, Patrick; Hue, Guy; Dreyfus, Jean-François; Woodhams, Barry; Vasse, Marc

2014-01-01

199

Loop-Mediated Isothermal Amplification Assay for Detection of Haemophilus influenzae Type b in Cerebrospinal Fluid?  

PubMed Central

Haemophilus influenzae type b (Hib) is one of the leading causes of meningitis in developing countries. To establish and evaluate a novel loop-mediated isothermal amplification (LAMP) assay for Hib, we designed a LAMP primer set targeting the Hib-specific capsulation locus. LAMP detected 10 copies of purified DNA in a 60-min reaction. This indicated that the detection limit of LAMP was >100-fold lower than the detection limits of both a PCR for the detection of bexA and a nested PCR for Hib (Hib PCR). No H. influenzae, other than Hib or control bacteria, was detected. Linear determination ranged from 10 to 1,000,000 microorganisms per reaction mixture using real-time turbidimetry. We evaluated the Hib LAMP assay using a set of 52 randomly selected cerebrospinal fluid (CSF) specimens obtained from children with suspected meningitis. For comparison, the CSF specimens were tested using a conventional Hib PCR assay. Hib was detected in 30 samples using LAMP and in 22 samples using the Hib PCR assay. The Hib PCR showed a clinical sensitivity of 73.3% and a clinical specificity of 100% relative to the Hib LAMP assay. These results suggest that further development and evaluation of the Hib LAMP will enhance the global diagnostic capability for Hib detection. PMID:21832019

Kim, Dong Wook; Kilgore, Paul Evan; Kim, Eun Jin; Kim, Soon Ae; Anh, Dang Duc; Seki, Mitsuko

2011-01-01

200

An alternative method of chronic cerebrospinal fluid collection via the cisterna magna in conscious rhesus monkeys.  

PubMed

Models of chronic cerebrospinal fluid (CSF) collection previously have been established for nonhuman primates and canines; many of these methods implement stainless-steel cannulas into the lateral or 4th ventricles or catheters into the cerebral or spinal subarachnoid space. These models have proved successful and reliable but unfortunately require invasive techniques to pass through the skull or require a laminectomy to enter the spinal subarachnoid space, involve the use of expensive and highly specialized stereotaxic equipment for the precise placement of the implants, and may require exteriorized hardware which is cumbersome to maintain and unaesthetic. The model we developed for the rhesus monkey allows for direct access to CSF outflow from the cisterna magna by using a 3.5-French fenestrated silicone catheter which was placed 1.0 cm into the cisterna. The catheter was attached to a titanium port placed subcutaneously between the scapulae to permit easy access for sampling CSF in a conscious, chaired rhesus monkey. We currently have instrumented animals from which we have consistently collected CSF for over 18 months. This novel, economical, less-invasive method permits chronic, reliable collection of CSF in conscious rhesus monkeys and has the additional advantages that the model is easier to maintain and more aesthetic. PMID:12906404

Gilberto, David B; Zeoli, Angela H; Szczerba, Peter J; Gehret, John R; Holahan, Marie A; Sitko, Gary R; Johnson, Colena A; Cook, Jacquelynn J; Motzel, Sherri L

2003-07-01

201

Polyol profiles in Down syndrome. myo-Inositol, specifically, is elevated in the cerebrospinal fluid.  

PubMed Central

Polyols are reduction products of aldoses and ketoses; their concentrations in tissues can reflect carbohydrate metabolism. Several polyol species were quantitated in cerebrospinal fluid (CSF) and plasma from 10 Down Syndrome (trisomy 21) subjects between the ages of 22 and 63 years (3 of whom were demented) and from 10 healthy age-matched controls, using a gas chromatographic/mass spectrometric technique. The mean CSF concentration and the mean CSF/plasma concentration ratio of myo-inositol were significantly elevated in Down syndrome compared with controls, but were not correlated with the presence of dementia in the Down subjects. Plasma myo-inositol was not significantly altered in these subjects. No significant difference between Down syndrome and controls was found for CSF concentrations of mannitol, sorbitol, galactitol, ribitol, arabitol, or 1,5-anhydrosorbitol, but plasma mannitol, ribitol and arabitol were elevated in Down syndrome. The present observation provides new impetus for studying synthesis and transport of myo-inositol as well as phosphatidylinositol cycle in trisomy 21 disorder. PMID:7860736

Shetty, H U; Schapiro, M B; Holloway, H W; Rapoport, S I

1995-01-01

202

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

PubMed Central

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

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

2014-01-01

203

ID3 contributes to cerebrospinal fluid seeding and poor prognosis in medulloblastoma  

PubMed Central

Background The inhibitor of differentiation (ID) genes have been implicated as promoters of tumor progression and metastasis in many human cancers. The current study investigated the expression and functional roles of ID genes in seeding and prognosis of medulloblastoma. Methods ID gene expression was screened in human medulloblastoma tissues. Knockdown of ID3 gene was performed in medulloblastoma cells in vitro. The expression of metastasis-related genes after ID3 knockdown was assessed. The effect of ID3 knockdown on tumor seeding was observed in an animal model in vivo. The survival of medulloblastoma patients was plotted according to the ID3 expression levels. Results Significantly higher ID3 expression was observed in medulloblastoma with cerebrospinal fluid seeding than tumors without seeding. Knockdown of ID3 decreased proliferation, increased apoptosis, and suppressed the migration of D283 medulloblastoma cells in vitro. In a seeding model of medulloblastoma, ID3 knockdown in vivo with shRNA inhibited the growth of primary tumors, prevented the development of leptomeningeal seeding, and prolonged animal survival. High ID3 expression was associated with shorter survival of medulloblastoma patients, especially in Group 4 medulloblastomas. Conclusions High ID3 expression is associated with medullolbastoma seeding and is a poor prognostic factor, especially in patients with Group 4 tumors. ID3 may represent the metastatic/ aggressive phenotype of a subgroup of medulloblastoma. PMID:23768125

2013-01-01

204

Picornaviruses in cerebrospinal fluid of children with meningitis in Luanda, Angola.  

PubMed

Human enteroviruses are the most common cause of viral meningitis. Viral-bacterial interaction may affect the clinical course and outcome of bacterial meningitis. In Africa, viruses might be responsible for 14-25% of all meningitis cases. However, only few studies from Africa have reported detection of viruses in the cerebrospinal fluid (CSF) or mixed viral-bacterial infections of the central nervous system (CNS). The aim of the present study was to investigate the presence of picornaviruses in the CSF of children suffering from meningitis in Luanda, Angola. The study included 142 consecutive children enrolled in a prospective study of bacterial meningitis in Luanda between 2005 and 2006, from whom a CSF sample was available. CSF samples were obtained at hospital admission, stored in a deep-freeze, and transported to Finland for testing by real-time PCR for picornaviruses. Enteroviruses were detected in 4 (3%) of 142 children with presumed bacterial meningitis. A 5-month-old girl with rhinovirus and Haemophilus influenzae meningitis recovered uneventfully. An 8-year-old girl with human enterovirus and pneumococcal meningitis developed no sequelae. A 2-month-old girl with human enterovirus and malaria recovered quickly. A 7-month-old girl with human enterovirus was treated for presumed tuberculous meningitis and survived with severe sequelae. Mixed infections of the CNS with picornaviruses and bacteria are rare. Detection of an enterovirus does not affect the clinical picture and outcome of bacterial meningitis. PMID:22585725

Pelkonen, Tuula; Roine, Irmeli; Anjos, Elizabete; Kaijalainen, Svetlana; Roivainen, Merja; Peltola, Heikki; Pitkäranta, Anne

2012-07-01

205

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

PubMed Central

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

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

206

Flowing cerebrospinal fluid in normal and hydrocephalic states: Appearance on MR images  

SciTech Connect

The signal intensity of the cerebrospinal fluid (CSF) in the cerebral aqueduct and lateral ventricles on magnetic resonance (MR) images was evaluated in 16 healthy individuals and in 32 patients with various forms of hydrocephalus (20 with chronic normal pressure hydrocephalus (NPH), seven with acute communicating hydrocephalus, and five with hydrocephalus ex vacuo (atrophy)). The low signal intensity frequently observed in the cerebral aqueduct is believed to reflect the pulsatile motion of CSF, which is related to the cardiac cycle. While this aqueductal flow void phenomenon can be observed in healthy individuals, it is most pronounced in patients with chronic, communicating NPH; is less evident in patients with acute, communicating hydrocephalus and is least evident in patients with atrophy. Ventricular compliance is known to be essentially normal in atrophy, mildly decreased in acute, communicating hydrocephalus; and severely decreased in NPH. The degree of aqueductal signal loss is believed to reflect the velocity of the pulsatile CSF motion, which in turn depends on the relative ventricular compliance and surface area.

Bradley, W.G.; Kortman, K.E.; Burgoyne, B.; Eng, D.

1986-06-01

207

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

PubMed

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

Oreškovi?, Darko; Klarica, Marijan

2014-08-28

208

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

PubMed Central

The generally accepted hypothesis on cerebrospinal fluid (CSF) hydrodynamics suggests that CSF is actively formed mainly by 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 method 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

Oreškovi?, Darko; Klarica, Marijan

2014-01-01

209

Elevated levels of phosphorylated neurofilament proteins in cerebrospinal fluid of Alzheimer disease patients.  

PubMed

Neurofilament (NF) subunits NF-H, NF-M and NF-L are hyperphosphorylated and elevated in Alzheimer disease (AD) brain. We investigated the level and phosphorylation states of NF subunits in lumbar cerebrospinal fluid (CSF) from living patients by bienzyme substrate-recycle enzyme-linked immunosorbent assay. We found: (i), that the levels of phosphorylated NF-H/M (pNF-H/M), non-phosphorylated NF-H/M (npNF-H/M) and NF-L were significantly higher (pNF-H/M, approximately 12-24-fold; npNF-H/M, approximately 3-4-fold) in neurologically healthy aged people than young control individuals; (ii), that in AD, the levels of npNF-H/M, and NF-L were similar to vascular dementia (VaD), and higher than in age-matched controls; and (iii), that the levels of pNF-H/M were significantly higher than in aged controls, non-AD neurological disorders and VaD. Based on these findings, it is suggested that the increased level of total NF proteins in CSF could be used as a marker for brain aging and neurodegenerative disorders in general, and the levels of pNF-H/M as a marker to discriminate AD from normal brain aging and as well as neurological conditions including VaD. PMID:11852185

Hu, Yuan-Yuan; He, Shan-Shu; Wang, Xiao-Chuang; Duan, Qiu-Hong; Khatoon, Sabiha; Iqbal, Khalid; Grundke-Iqbal, Inge; Wang, Jian-Zhi

2002-03-01

210

Measurement of fluorescent probes concentration ratio in the cerebrospinal fluid for early detection of Alzheimer's disease  

NASA Astrophysics Data System (ADS)

The pathogenic process of Alzheimer's Disease (AD), characterized by amyloid plaques and neurofibrillary tangles in the brain, begins years before the clinical diagnosis. Here, we suggest a novel method which may detect AD up to nine years earlier than current exams, minimally invasive, with minimal risk, pain and side effects. The method is based on previous reports which relate the concentrations of biomarkers in the Cerebrospinal Fluid (CSF) (A? and Tau proteins) to the future development of AD in mild cognitive impairment patients. Our method, which uses fluorescence measurements of the relative concentrations of the CSF biomarkers, replaces the lumbar puncture process required for CSF drawing. The process uses a miniature needle coupled trough an optical fiber to a laser source and a detector. The laser radiation excites fluorescent probes which were prior injected and bond to the CSF biomarkers. Using the ratio between the fluorescence intensities emitted from the two biomarkers, which is correlated to their concentration ratio, the patient's risk of developing AD is estimated. A theoretical model was developed and validated using Monte Carlo simulations, demonstrating the relation between fluorescence emission and biomarker concentration. The method was tested using multi-layered tissue phantoms simulating the epidural fat, the CSF in the sub-arachnoid space and the bone. These phantoms were prepared with different scattering and absorption coefficients, thicknesses and fluorescence concentrations in order to simulate variations in human anatomy and in the needle location. The theoretical and in-vitro results are compared and the method's accuracy is discussed.

Harbater, Osnat; Gannot, Israel

2014-03-01

211

Combined approach for tegmen defects repair in patients with cerebrospinal fluid otorrhea or herniations: our experience.  

PubMed

Objectives?To describe our departmental experience in the surgical repair of tegmen tympani defects using a combined transmastoid/minicraniotomic approach. Design?Retrospective review of videos from surgery and patients' charts. Setting?Tertiary university referral center. Participants?Twenty-two patients who underwent surgical repair of tegmen defects associated with cerebrospinal fluid (CSF) leakage and/or meningocele/meningoencephalocele by a combined transmastoid/minicraniotomic approach. Main Outcome Measures?A retrospective review of videos of surgery and charts of patients with tegmen tympani or tegmen antri defects and CSF leakage, temporal lobe encephalocele, and/or meningoencephalocele. Results?All patients underwent the combined approach and had their defects closed, without significant intraoperative or postoperative complications. Conclusions?Mastoidectomy with temporal minicraniotomy represents an effective approach in patients with tegmen tympani dehiscence; the advantages of this technique are the control of the floor of the middle cranial fossa and the possibility to reach bony defects located anteriorly without manipulation of the ossicular chain and temporal lobe. PMID:25093152

Marchioni, Daniele; Bonali, Marco; Alicandri-Ciufelli, Matteo; Rubini, Alessia; Pavesi, Giacomo; Presutti, Livio

2014-08-01

212

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

PubMed Central

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

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

2000-01-01

213

Serotonin metabolites in the cerebrospinal fluid in sudden infant death syndrome.  

PubMed

Forensic biomarkers are needed in sudden infant death syndrome (SIDS) to help identify this group among other sudden unexpected deaths in infancy. Previously, we reported multiple serotonergic (5-HT) abnormalities in nuclei of the medulla oblongata that help mediate protective responses to homeostatic stressors. As a first step toward their assessment as forensic biomarkers of medullary pathology, here we test the hypothesis that 5-HT-related measures are abnormal in the cerebrospinal fluid (CSF) of SIDS infants compared with those of autopsy controls. Levels of CSF 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), the degradative products of 5-HT and dopamine, respectively, were measured by high-performance liquid chromatography in 52 SIDS and 29 non-SIDS autopsy cases. Tryptophan (Trp) and tyrosine (Tyr), the substrates of 5-HT and dopamine, respectively, were also measured. There were no significant differences in 5-HIAA, Trp, HVA, or Tyr levels between the SIDS and non-SIDS groups. These data preclude the use of 5-HIAA, HVA, Trp, or Tyr measurements as CSF autopsy biomarkers of 5-HT medullary pathology in infants who have died suddenly and unexpectedly. They do, however, provide important information about monoaminergic measurements in human CSF at autopsy and their developmental profile in infancy that is applicable to multiple pediatric disorders beyond SIDS. PMID:24423636

Rognum, Ingvar J; Tran, Hoa; Haas, Elisabeth A; Hyland, Keith; Paterson, David S; Haynes, Robin L; Broadbelt, Kevin G; Harty, Brian J; Mena, Othon; Krous, Henry F; Kinney, Hannah C

2014-02-01

214

Novel myelin penta- and hexa-acetyl-galactosyl-ceramides: structural characterization and immunoreactivity in cerebrospinal fluid.  

PubMed

Fast migrating cerebrosides (FMC) are derivatives of galactosylceramide (GalCer). The structures of the most hydrophobic FMC-5, FMC-6, and FMC-7 were determined by electrospray ionization linear ion-trap mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy complementing previous NMR spectroscopy and gas chromatography-mass spectrometry to be 3-O-acetyl-sphingosine-GalCer derivatives with galactose O-acetyl modifications. FMC-5 and FMC-6 are 3-O-acetyl-sphingosine-2,3,4,6-tetra-O-acetyl-GalCer with nonhydroxy and hydroxy-N-fatty-acids, while FMC-7 has an additional O-acetylation of the 2-hydroxy-fatty acid. The immuno-reactivity in human cerebrospinal fluid (CSF) to these acetylated glycolipids was examined in central nervous system (CNS) infectious disease, noninflammatory disorders, and multiple sclerosis (MS). Screening for lipid binding in MS and other neurological disease groups revealed that the greatest anti-hydrophobic FMC reactivity was observed in the inflammatory CNS diseases (meningitis, meningo-encephalitis, and subacute sclerosing panencephalitis). Some MS patients had increased reactivity with the hydrophobic FMCs and with glycoglycerophospholipid MfGL-II from Mycoplasma fermentans. The cross-reactivity of highly acetylated GalCer with microbial acyl-glycolipid raises the possibility that myelin-O-acetyl-cerebrosides, bacterial infection, and neurological disease are linked. PMID:20154333

Podbielska, Maria; Dasgupta, Somsankar; Levery, Steven B; Tourtellotte, Wallace W; Annuk, Heidi; Moran, Anthony P; Hogan, Edward L

2010-06-01

215

Total tau is increased, but phosphorylated tau not decreased, in cerebrospinal fluid in amyotrophic lateral sclerosis.  

PubMed

In amyotrophic lateral sclerosis (ALS), objective biomarkers are needed for early diagnosis and progression monitoring. Reduced phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) has recently been proposed to provide such a biomarker in ALS. Here, we aimed to scrutinize this notion, evaluating both p-tau and total tau (t-tau) in CSF of ALS patients and control subjects. CSF p-tau and t-tau levels were measured in 60 consecutive ALS patients and 120 control subjects without neurodegenerative disease, using an established specific enzyme-linked immunosorbent assay method. Contrary to recent reports, CSF p-tau was not significantly reduced in ALS patients compared with control subjects (p = 0.287). However, CSF t-tau was significantly increased (p < 0.001). Correspondingly, the ratio of p-tau to t-tau was significantly reduced in ALS (p < 0.001). The area under the curve demonstrated poor sensitivity and specificity for p-tau, but moderate sensitivity and specificity for t-tau and p-tau/t-tau ratio. Thus, CSF p-tau by itself does not appear a suitable diagnostic biomarker for ALS, whereas CSF t-tau is a (probably unspecific) marker of the neuronal degeneration in ALS. PMID:25453560

Wilke, Carlo; Deuschle, Christian; Rattay, Tim W; Maetzler, Walter; Synofzik, Matthis

2015-02-01

216

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

PubMed Central

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

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

2014-01-01

217

Sensitization of cerebrospinal fluid and peripheral blood lymphocytes to myelin basic protein in multiple sclerosis.  

PubMed

Cerebrospinal fluid (CSF) and peripheral blood (PB) lymphocyte sensitization to rabbit myelin basic protein (MBP) in 44 multiple sclerosis (MS) patients, 21 patients with other neurological diseases (OND) and 14 persons with neurosis was studied with the antigen-active rosette forming cells (Ag-ARFC) assay. The frequency of sensitization of CSF lymphocytes to MBP in groups of MS patients in the relapse stage and the chronic progressive stage was higher than in the group of MS patients in the stable stage and the OND patients. None of the healthy subjects showed a positive reaction with MBP. In BP there were no differences in the incidence of sensitization to MBP between patients in various stages of the disease, but it was higher than in the group of patients with OND and neuroses. In the patients who had suffered from MS for less than 4 years, sensitization to MBP was more common in CSF lymphocytes than in BP lymphocytes. The results suggest that primary sensitization to MBP occurs in CSF, and is probably secondary to myelin damage. However at present it is difficult to determine the extent to which sensitization of CSF and PB lymphocytes to MBP play a role in further demyelination processes. PMID:6180592

Cz?onkowska, A; Pó?torak, M; Cendrowski, W; Korlak, J

1982-07-01

218

Increased Levels of Chitotriosidase and YKL-40 in Cerebrospinal Fluid from Patients with Alzheimer's Disease  

PubMed Central

Background The cerebrospinal fluid (CSF) biomarkers total tau, abnormally phosphorylated tau and amyloid ? 1-42 are strongly associated with Alzheimer's disease (AD). Apart from the pathologic hallmarks that these biomarkers represent, other processes such as inflammation and microglial activation are present in the brains of patients with AD. New biomarkers related to these processes could be valuable for the diagnosis and follow-up of AD patients and for the evaluation of inflammation-related pathologies. Aim The aim of this study was to evaluate the association of inflammatory CSF biomarkers with AD. Methods Twenty-five AD patients and 25 controls who had a pathological and normal CSF profile of the core AD biomarkers, respectively, were included in this study. CSF levels of chitotriosidase, YKL-40 (also known as chitinase-3-like protein 1) and monocyte chemoattractant protein-1 (MCP-1) were quantified and the levels compared between the groups. Results AD patients had increased CSF levels of chitotriosidase and YKL-40 (both approximately twice higher than in controls), while the levels of MCP-1 were similar in the AD and control groups. Conclusion The results indicate that chitotriosidase and YKL-40 may be helpful for the evaluation of cerebral inflammatory activity in AD patients. PMID:25254036

Rosén, Christoffer; Andersson, Carl-Henrik; Andreasson, Ulf; Molinuevo, José L.; Bjerke, Maria; Rami, Lorena; Lladó, Albert; Blennow, Kaj; Zetterberg, Henrik

2014-01-01

219

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

PubMed

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

Cabral, A; Fernandez, G; Perello, M

2013-12-01

220

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

PubMed Central

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

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

2014-01-01

221

Ultrasound-guided atlanto-occipital puncture for cerebrospinal fluid analysis on the standing horse.  

PubMed

The atlanto-occipital site (AO) is convenient for retrieving an adequate volume and quality of cerebrospinal fluid (CSF) in the diagnosis of neurological disease in horses. However, general anaesthesia is not always possible for horses displaying severe neurological signs, or for economical reasons. The objectives of the present work were to determine the feasibility and safety of ultrasound-guided CSF puncture at the AO site on the standing horse. Seven horses (six healthy and one mildly ataxic) were sedated with acepromazine (0.02 mg/kg bodyweight intravenously or 0.04 mg/kg bodyweight intramuscularly) and detomidine (0.01 mg/kg bodyweight intravenously), and placed in stocks or in a recovery stall with the head kept on a headstand. Puncture was performed by ultrasonographic guidance with a parasagittal technique, as previously described, using a 20 g, 3.5 inch spinal needle. In all horses, no adverse reaction was observed when crossing the dura mater and 20 ml of CSF was rapidly retrieved without any blood contamination. Ultrasound-guided CSF puncture can be performed easily at the AO site on a healthy standing horse. Regarding the potential risk of this procedure, safety measures and close observation are essential. Further studies on a larger amount of ataxic horses are also required before considering this technique as an alternative option for CSF puncture. PMID:24225443

Depecker, M; Bizon-Mercier, C; Couroucé-Malblanc, A

2014-01-11

222

Failure of cerebrospinal fluid homovanillic acid to predict levodopa response in Parkinson's disease.  

PubMed

Lumbar cerebrospinal fluid homovanillic acid levels were estimated in 60 patients with Parkinsonism before and during levodopa treatment. There was a slight negative correlation between pretreatment CSF homovanillic acid levels and disability. There was no correlation between pretreatment homovanillic acid levels and clinical response to levodopa. Patients with high pretreatment levels did as well as those with depressed levels. High (normal or near normal) levels of CSF homovanillic acid in a patient with Parkinsonism do not necessarily indicate that the Parkinsonism will not respond to levodopa. These patients should receive the benefit of a trial of levodopa. There was also no correlation between homovanillic acid level during tratment and improvement. Patients with minimal increases in CSF homovanillic acid responded as well as those with greater elevations. Failure of levodopa to increase CSF homovanillic acid significantly does not indicate that the patient will not respond to levodopa and that levodopa should be discontinued. Other factors, such as vitamin B(6) consumption, should be investigated. PMID:4753871

Weiner, W J; Klawans, H L

1973-10-01

223

Elevated concentrations of neurofilament light chain in the cerebrospinal fluid of bipolar disorder patients.  

PubMed

Bipolar disorder (BD) is characterized by mood swings between manic and depressive states. The etiology and pathogenesis of BD is unclear, but many of the affected cognitive domains, as well as neuroanatomical abnormalities, resemble symptoms and signs of small vessel disease. In small vessel disease, cerebrospinal fluid (CSF) markers reflecting damages in different cell types and subcellular structures of the brain have been established. Hence, we hypothesized that CSF markers related to small vessel disease may also be applicable as biomarkers for BD. To investigate this hypothesis, we sampled CSF from 133 patients with BD and 86 healthy controls. The concentrations of neurofilament light chain (NF-L), myelin basic protein (MBP), S100B, and heart-type fatty acid binding protein (H-FABP) were measured in CSF and analyzed in relation to diagnosis, clinical characteristics, and ongoing medications. Hereby we found an elevation of the marker of subcortical axonal damage, NF-L, in bipolar subjects. We also identified positive associations between NF-L and treatment with atypical antipsychotics, MBP and lamotrigine, and H-FABP and lithium. These findings indicate axonal damage as an underlying neuropathological component of bipolar disorder, although the clinical value of elevated NF-L remains to be validated in follow-up studies. The associations between current medications and CSF brain injury markers might aid in the understanding of both therapeutic and adverse effects of these drugs. PMID:24694925

Jakobsson, Joel; Bjerke, Maria; Ekman, Carl Johan; Sellgren, Carl; Johansson, Anette G M; Zetterberg, Henrik; Blennow, Kaj; Landén, Mikael

2014-09-01

224

Proteomic profiling of cerebrospinal fluid identifies biomarkers for amyotrophic lateral sclerosis.  

PubMed

Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motor neurons. We tested the hypothesis that proteomic analysis will identify protein biomarkers that provide insight into disease pathogenesis and are diagnostically useful. To identify ALS specific biomarkers, we compared the proteomic profile of cerebrospinal fluid (CSF) from ALS and control subjects using surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF-MS). We identified 30 mass ion peaks with statistically significant (p < 0.01) differences between control and ALS subjects. Initial analysis with a rule-learning algorithm yielded biomarker panels with diagnostic predictive value as subsequently assessed using an independent set of coded test subjects. Three biomarkers were identified that are either decreased (transthyretin, cystatin C) or increased (carboxy-terminal fragment of neuroendocrine protein 7B2) in ALS CSF. We validated the SELDI-TOF-MS results for transthyretin and cystatin C by immunoblot and immunohistochemistry using commercially available antibodies. These findings identify a panel of CSF protein biomarkers for ALS. PMID:16313519

Ranganathan, Srikanth; Williams, Eric; Ganchev, Philip; Gopalakrishnan, Vanathi; Lacomis, David; Urbinelli, Leo; Newhall, Kristyn; Cudkowicz, Merit E; Brown, Robert H; Bowser, Robert

2005-12-01

225

Proteomic profiling of cerebrospinal fluid identifies biomarkers for amyotrophic lateral sclerosis  

PubMed Central

Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motor neurons. We tested the hypothesis that proteomic analysis will identify protein biomarkers that provide insight into disease pathogenesis and are diagnostically useful. To identify ALS specific biomarkers, we compared the proteomic profile of cerebrospinal fluid (CSF) from ALS and control subjects using surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF-MS). We identified 30 mass ion peaks with statistically significant (p < 0.01) differences between control and ALS subjects. Initial analysis with a rule-learning algorithm yielded biomarker panels with diagnostic predictive value as subsequently assessed using an independent set of coded test subjects. Three biomarkers were identified that are either decreased (transthyretin, cystatin C) or increased (carboxy-terminal fragment of neuroendocrine protein 7B2) in ALS CSF. We validated the SELDI-TOF-MS results for transthyretin and cystatin C by immunoblot and immunohistochemistry using commercially available antibodies. These findings identify a panel of CSF protein biomarkers for ALS. PMID:16313519

Ranganathan, Srikanth; Williams, Eric; Ganchev, Philip; Gopalakrishnan, Vanathi; Lacomis, David; Urbinelli, Leo; Newhall, Kristyn; Cudkowicz, Merit E.; Brown, Robert H.; Bowser, Robert

2006-01-01

226

Unilateral Endoscopic Approach for Repair of Frontal Sinus Cerebrospinal Fluid Leak  

PubMed Central

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

Roehm, Corrie E.; Brown, Seth M.

2011-01-01

227

Tissue inhibitors of matrix metalloproteinases are elevated in cerebrospinal fluid of neurodegenerative diseases.  

PubMed

Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of diseases such as Alzheimer's Disease (AD) and amyotrophic lateral sclerosis (ALS). Increased expression of MMP-9 and TIMPs has been reported in postmortem AD and ALS brain tissue, as well as in ALS cerebrospinal fluid (CSF) and plasma. Although individual studies of MMP and TIMP expression in CSF have included AD and ALS samples, there are no studies comparing the expression of these proteins between neurodegenerative diseases. We measured the levels of matrix metalloproteinases (MMPs)-2 and -9 and the tissue inhibitor of MMPs (e.g. TIMP-1 and TIMP-2) in CSF samples from patients with Parkinson's Disease (PD), Huntington's Disease (HD), AD and ALS as compared to age-matched control patients. There was constitutive expression of the proform of gelatinase A (proMMP-2) on zymography gels in all CSF samples. Unexpectedly, there was an additional gelatinolytic band at 130 kDa of unknown etiology in the CSF samples of patients with PD (61% of patients studied), AD (61%), HD (25%) and ALS (39%). Levels of TIMP-1 were significantly elevated in CSF samples from all disease groups. TIMP-2 was significantly increased in CSF of AD and HD patients. MMP-2 levels did not differ significantly between groups. These findings show that TIMPs are elevated in the CSF of patients with neurodegenerative diseases suggesting a potential role of these endogenous inhibitors of matrix metalloproteinases in neurodegenerative diseases. PMID:12614934

Lorenzl, S; Albers, D S; LeWitt, P A; Chirichigno, J W; Hilgenberg, S L; Cudkowicz, M E; Beal, M F

2003-03-15

228

Axon reactive B cells clonally expanded in the cerebrospinal fluid of patients with multiple sclerosis.  

PubMed

Demyelination and axonal loss have been described as the histological hallmarks of inflammatory lesions of multiple sclerosis (MS) and are the pathological correlates of persistent disability. However, the immune mechanisms underlying axonal damage in MS remain unknown. Here, we report the use of single chain-variable domain fragments (scFv) from clonally expanded cerebrospinal fluid (CSF) B cells to show the role of an anti-axon immune response in the central nervous system (CNS) in MS. The cellular and subcellular distribution of the antigen(s) recognized by these CSF-derived clonal scFv antibodies (CSFC-scFv Abs) was studied by immunochemical staining of brain tissues obtained at autopsy from patients with MS. Immunochemistry showed specific binding of CSFC-scFv Abs to axons in acute MS lesions. The stained axons showed three major types of axonal pathological changes: 1) linear axons, axonal ovoid formation, and axonal transection were seen in the myelinated white matter adjacent to the lesion; 2) accumulation of axonal ovoid formations and Wallerian degeneration were seen at the border between demyelinated lesions and the adjacent white matter; and 3) Wallerian degeneration occurred at the center and edge of acute demyelinated lesions. These findings suggest a B cell axonal specific immune response in the CNS in MS. PMID:15981091

Zhang, Yiping; Da, Reng-Rong; Guo, Wenzhong; Ren, Hui-Min; Hilgenberg, Lutz G; Sobel, Raymond A; Tourtellotte, Wallace W; Smith, Martin A; Olek, Michael; Gupta, Sudhir; Robertson, Richard T; Nagra, Rashed; Van Den Noort, Stanley; Qin, Yufen

2005-05-01

229

Cerebrospinal fluid soluble L-selectin (sCD62L) in meningoencephalitis.  

PubMed Central

The leucocyte adhesion molecule L-selectin (CD62L) is rapidly cleaved off proteolytically after cell activation, generating soluble L-selectin (sCD62L) molecules. sCD62L concentrations were determined in 185 cerebrospinal fluid (CSF) samples obtained from children aged 1 month to 17 years. In 36 CSF samples of children with meningoencephalitis, sCD62L was significantly higher (median 209 fmol/ml) than in samples of children with other febrile diseases (n = 67, median 50 fmol/ml) or non-febrile disorders (n = 82, median 44 fmol/ml). There was a positive correlation between CSF protein and CSF sCD62L (rS = 0.68), suggesting that a disturbed blood-brain barrier contributes to raised sCD62L concentrations in the CSF. However, the CSF sCD62L/protein ratio of children with meningoencephalitis was significantly higher than in children with other febrile diseases or non-febrile disorders, indicating that sCD62L concentrations in children with meningoencephalitis were higher than expected from plasma leakage alone. It is concluded that both an impaired blood-brain barrier and the generation of sCD62L by infiltrating leucocytes contribute to raised CSF sCD62L concentrations in children with meningoencephalitis. PMID:8669926

Bührer, C; Herold, R; Stibenz, D; Henze, G; Obladen, M

1996-01-01

230

Cerebrospinal Fluid Biomarkers and Proximity to Diagnosis in Preclinical Familial Alzheimer's Disease  

PubMed Central

Background/Aims: Biological markers of utility in tracking Alzheimer's disease (AD) during the presymptomatic prodromal phase are important for prevention studies. Changes in cerebrospinal fluid (CSF) levels of 42-amino-acid ?-amyloid (A?42), total tau protein (t-tau) and phosphorylated tau at residue 181 (p-tau181) during this state are incompletely characterized. Methods We measured CSF markers in 13 carriers of familial AD (FAD) mutations that are fully penetrant for causing AD (PSEN1 and APP) and in 5 non-mutation-carrying family members. Results Even among the entirely presymptomatic mutation carriers (n = 9), A?42 was diminished (388.7 vs. 618.4 pg/ml, p = 0.004), and t-tau (138.5 vs. 50.5 pg/ml, p = 0.002) and p-tau181 (71.7 vs. 24.6 pg/ml, p = 0.003) were elevated. There was a negative correlation between A?42 levels and age relative to the family-specific age of dementia diagnosis. Conclusions Our data are consistent with a decline in CSF A?42 levels occurring at least 20 years prior to clinical dementia in FAD. PMID:22343824

Ringman, John M.; Coppola, Giovanni; Elashoff, David; Rodriguez-Agudelo, Yaneth; Medina, Luis D.; Gylys, Karen; Cummings, Jeffrey L.; Cole, Greg M.

2012-01-01

231

Conformation-Dependent Oligomers in Cerebrospinal Fluid of Presymptomatic Familial Alzheimer's Disease Mutation Carriers  

PubMed Central

Background/Aims Oligomerization of amyloid beta (A?) is a hypothesized step in the formation of plaques in Alzheimer's disease (AD) but has been difficult to demonstrate in vivo in humans. As persons destined to develop familial AD (FAD) due to fully penetrant autosomal dominant mutations are essentially certain to develop the disease, they provide the opportunity to identify oligomers during the presymptomatic stage of the disease. Methods We measured levels of A?42 using a conventional immunoassay and prefibrillar, fibrillar, and annular protofibrillar oligomers using polyclonal conformation-dependent antibodies in the cerebrospinal fluid (CSF) of 7 persons at risk for inheriting FAD mutations. Levels of oligomers were compared between FAD mutation carriers and noncarriers. Results Compared to 2 noncarriers, annular protofibrillar oligomers were elevated, prefibrillar and fibrillar oligomers trended towards elevation and A?42 monomer trended towards being decreased in 5 FAD mutation carriers. Conclusion Our data provide evidence for an identifiable elevation of CSF oligomers during the presymptomatic phase of FAD. PMID:23341831

Ringman, John M.; Tomic, Jennifer L.; Coppola, Giovanni; Elashoff, David; Gylys, Karen H.; Glabe, Charles G.

2012-01-01

232

Changes in kinetics of amino acid uptake at the ageing ovine blood-cerebrospinal fluid barrier.  

PubMed

Amino acids (AA) in brain are precisely controlled by blood-brain barriers, which undergo a host of changes in both morphology and function during ageing. The effect of these age-related changes on AA homeostasis in brain is not well described. This study investigated the kinetics of four AA (Leu, Phe, Ala and Lys) uptakes at young and old ovine choroid plexus (CP), the blood-cerebrospinal fluid (CSF) barrier (BCB), and measured AA concentrations in CSF and plasma samples. In old sheep, the weight of lateral CP increased, so did the ratio of CP/brain. The expansion of the CP is consistent with clinical observation of thicker leptomeninges in old age. AA concentrations in old CSF, plasma and their ratio were different from the young. Both V(max) and K(m) of Phe and Lys were significant higher compared to the young, indicating higher trans-stimulation in old BCB. Cross-competition and kinetic inhibition studies found the sensitivity and specificity of these transporters were impaired in old BCB. These changes may be the first signs of a compromised barrier system in ageing brain leading increased AA influx into the brain causing neurotoxicity. PMID:20138405

Chen, R L; Preston, J E

2012-01-01

233

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

PubMed Central

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

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

234

Cerebrospinal Fluid Metabolome in Mood Disorders-Remission State has a Unique Metabolic Profile  

PubMed Central

Targeted metabolomics provides an approach to quantify metabolites involved in specific molecular pathways. We applied an electrochemistry-based, targeted metabolomics platform to define changes in tryptophan, tyrosine, purine and related pathways in the depressed and remitted phases of major depressive disorder (MDD). Biochemical profiles in the cerebrospinal fluid of unmedicated depressed (n = 14; dMDD) or remitted MDD subjects (n = 14; rMDD) were compared against those in healthy controls (n = 18; HC). The rMDD group showed differences in tryptophan and tyrosine metabolism relative to the other groups. The rMDD group also had higher methionine levels and larger methionine-to-glutathione ratios than the other groups, implicating methylation and oxidative stress pathways. The dMDD sample showed nonsignificant differences in the same direction in several of the metabolic branches assessed. The reductions in metabolites associated with tryptophan and tyrosine pathways in rMDD may relate to the vulnerability this population shows for developing depressive symptoms under tryptophan or catecholamine depletion. PMID:22993692

Kaddurah-Daouk, Rima; Yuan, Peixiong; Boyle, Stephen H.; Matson, Wayne; Wang, Zhi; Zeng, Zhao Bang; Zhu, Hongjie; Dougherty, George G.; Yao, Jeffrey K.; Chen, Guang; Guitart, Xavier; Carlson, Paul J.; Neumeister, Alexander; Zarate, Carlos; Krishnan, Ranga R.; Manji, Husseini K.; Drevets, Wayne

2012-01-01

235

In-use stability of monoamine metabolites in human cerebrospinal fluid.  

PubMed

Cerebrospinal fluid (CSF) concentrations of the monoamine metabolites homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA) are commonly used to provide information about central nervous system (CNS) dopaminergic and serotonergic activity. However, little attention has been given to the effects of sample handling on the concentrations of these compounds in human CSF. Using high-performance liquid chromatography (HPLC) with electrochemical detection, we observed that, in CSF stored at -80 degrees C, concentrations of the serotonin metabolite 5-HIAA and the dopamine metabolite HVA remained unchanged through six 1-h and six 24-h freeze-thaw cycles. Exposure to bright room light (3 h, 1,230 lux) resulted in a 5-HIAA concentration that was 96.3 +/- 2.0% of the initial and an HVA concentration that was 98.8 +/- 1.03% of initial. The pH of the CSF significantly increased during both freeze-thaw series and while maintained on ice (4 degrees C). These results demonstrate the in-use stability of 5-HIAA and HVA in human CSF under commonly-encountered laboratory conditions. PMID:11530989

Strawn, J R; Ekhator, N N; Geracioti, T D

2001-09-01

236

TLTF in Cerebrospinal Fluid for Detection and Staging of T. b. gambiense Infection  

PubMed Central

Background Trypanosome-derived lymphocyte triggering factor (TLTF) is a molecule released by African trypanosomes that interacts with the host immune system, resulting in increased levels of IFN-? production. Methodology/Principal findings TLTF and anti-TLTF antibodies were assessed in sera and cerebrospinal fluid (CSF) from patients infected with Trypanosoma brucei gambiense (T. b. gambiense) in an attempt to identify alternative markers for diagnosis and stage determination of human African trypanosomiasis or sleeping sickness. Seventy-four serum and sixty-one CSF samples from patients with parasitologically confirmed infection and known disease stage along with 13 sera and CSF from uninfected controls were tested. In serum the levels of anti-TLTF antibodies were unrelated to the disease stage. In contrast, levels of anti-TLTF antibodies in CSF were higher in intermediate/late stages than in early stage disease patients. Specificity of the detected antibodies was assessed by inhibition of TLTF bioactivity as represented by its ability to induce IFN-? production. Additionally, TLTF was detected in CSF from late stage patients by Western blotting with the anti-TLTF specific monoclonal antibody MO3. Conclusions/Significance These findings suggest a new possibility for disease diagnosis with focus on involvement of the CNS through detection of TLTF and anti-TLTF antibodies in the CSF. PMID:24260185

Abdulla, Maha-Hamadien; Bakhiet, Moiz; Lejon, Veerle; Andersson, Jan; McKerrow, James; Al-Obeed, Omar; Harris, Robert A.

2013-01-01

237

The regulation of brain states by neuroactive substances distributed via the cerebrospinal fluid; a review  

PubMed Central

The cerebrospinal fluid (CSF) system provides nutrients to and removes waste products from the brain. Recent findings suggest, however, that in addition, the CSF contains message molecules in the form of actively released neuroactive substances. The concentrations of these vary between locations, suggesting they are important for the changes in brain activity that underlie different brain states, and induce different sensory input and behavioral output relationships. The cranial CSF displays a rapid caudally-directed ventricular flow followed by a slower rostrally-directed subarachnoid flow (mainly towards the cribriform plate and from there into the nasal lymphatics). Thus, many brain areas are exposed to and can be influenced by substances contained in the CSF. In this review we discuss the production and flow of the CSF, including the mechanisms involved in the regulation of its composition. In addition, the available evidence for the release of neuropeptides and other neuroactive substances into the CSF is reviewed, with particular attention to the selective effects of these on distant downstream receptive brain areas. As a conclusion we suggest that (1) the flowing CSF is involved in more than just nutrient and waste control, but is also used as a broadcasting system consisting of coordinated messages to a variety of nearby and distant brain areas; (2) this special form of volume transmission underlies changes in behavioral states. PMID:20157443

2010-01-01

238

Cerebrospinal fluid drainage and cranial decompression prolong survival in rats with fulminant hepatic failure  

PubMed Central

Summary Fulminant hepatic failure (FHF) is a devastating disease. Liver transplantation is the definitive treatment. However, a third of these patients die due to brain edema before a donor becomes available. Cerebrospinal fluid (CSF) drainage and decompressive craniectomy have been used to treat brain edema in brain trauma and hemispheric stroke. However, their role in brain edema associated with FHF has not been examined. In this study we evaluated the potential effects of CSF drainage and decompressive craniectomy on survival in FHF using an experimental model in rats. In CSF drainage experiments all animals had ventriculostomy placed. Five days later FHF was induced with d-galactosamine. Those FHF rats that progressed into comatose stages either received CSF aspiration or did not. In separate experiments the study rats had either a decompressive craniectomy or a sham procedure. FHF was induced 5 days later. We found that both CSF drainage and decompressive craniectomy significantly increased survival of FHF rats compared with the controls: 53.2 ± 1.1 vs. 48.7 ± 1.5 h (P = 0.031), and 69.4 ± 3.9 vs. 53.7 ± 3.2 h (P = 0.009), respectively. In conclusion, these findings suggest that CSF drainage and decompressive craniectomy may increase the window of opportunity for liver transplantation. PMID:16827685

Yamamoto, Satoshi; Steers, Jeffery L.; Wharen, Robert E.; Eckman, Christopher B.; Nguyen, Justin H.

2009-01-01

239

Systemic pharmacokinetics and cerebrospinal fluid uptake of intravenous ceftriaxone in patients with amyotrophic lateral sclerosis.  

PubMed

The cephalosporin antibiotic ceftriaxone was evaluated as a potential therapeutic agent for the treatment of amyotrophic lateral sclerosis (ALS). The pharmacokinetics (PK) of ceftriaxone in plasma and cerebrospinal fluid (CSF) were investigated in 66 participants in a previously reported clinical trial. Their mean age was 51 years, and 65% were male. Participants were randomly assigned to 1 of 3 treatment groups receiving intravenous infusions (mean duration: 25 minutes) every 12 hours of either: placebo and placebo; 2 g ceftriaxone and placebo; or 2 g ceftriaxone twice. Mean steady-state plasma PK variables were: volume of distribution, 14 L (0.17 L/kg); elimination half-life, 8-9 h; total clearance, 17-21 mL/min (0.22-0.25 mL/min/kg). Values were not different between dosage groups. CSF PK analysis, determined through sparse CSF sampling, indicated apparent entry and elimination half-life values of 1.0 and 34 hours, respectively. With both dosage regimens, CSF concentrations were maintained above the target threshold of 1.0 µM (0.55 µg/mL) as determined from in vitro models. The plasma and CSF PK profiles of ceftriaxone were used as a basis for planning the Phase 3 clinical trial of ceftriaxone in ALS. PMID:24771634

Zhao, Yanli; Cudkowicz, Merit E; Shefner, Jeremy M; Krivickas, Lisa; David, William S; Vriesendorp, Francine; Pestronk, Alan; Caress, James B; Katz, Jonathan; Simpson, Ericka; Rosenfeld, Jeffrey; Pascuzzi, Robert; Glass, Jonathan; Rezania, Kourosh; Harmatz, Jerold S; Schoenfeld, David; Greenblatt, David J

2014-10-01

240

Dosimetric model for antibody targeted radionuclide therapy of tumor cells in cerebrospinal fluid  

SciTech Connect

Although encouraging results have been obtained using systemic radioimmunotherapy in the treatment of cancer, it is likely that regional applications may prove more effective. One such strategy is the treatment of central nervous system leukemia in children by intrathecal instillation of targeting or nontargeting beta particle emitting radionuclide carriers. The beta particle dosimetry of the spine is assessed, assuming that the spinal cord and the cerebrospinal fluid compartment can be adequately represented by a cylindrical annulus. The radionuclides investigated were {sup 90}Y, {sup 131}I, {sup 67}Cu, and {sup 199}Au. It is shown that the radiation dose to the cord can be significantly reduced using short range beta particle emitters and that there is little advantage in using targeting carriers with these radionuclides. {sup 199}Au and {sup 67}Cu also have the advantage of having a suitable gamma emission for imaging, permitting pretherapy imaging and dosimetric calculations to be undertaken prior to therapy. If these methods prove successful, it may be possible to replace the external beam component used in the treatment of central nervous system leukemia in children by intrathecal radionuclide therapy, thus reducing or avoiding side effects such as growth and intellectual impairment.

Millar, W.T.; Barrett, A. (Univ. of Glasgow, Scotland (England))

1990-02-01

241

Cerebrospinal fluid T-regulatory cells recognize Borrelia burgdorferi NAPA in chronic Lyme borreliosis.  

PubMed

The NapA protein of B. burgdorferi is essential for the persistence of spirochetes in ticks. One of the most intriguing aspects of NapA is its potential to interfere with the host immune system. Here, we investigated the role of the acquired immune responses induced by NapA in the cerebrospinal fluids (CSF) of patients with chronic Lyme borreliosis. We evaluated the cytokine profile induced in microglia cells and CSF T cells following NapA stimulation. We report here that NapA induced a regulatory T (Treg) response in the CSF of patients with chronic Lyme borreliosis and it is able to expand this suppressive response by promoting the production of TGF-beta and IL-10 by microglia cells. Collectively, these data strongly support a central role of NapA in promoting both Treg response and immune suppression in the CSF of patients with chronic Lyme borreliosis and suggest that NapA and the Treg pathway may represent novel therapeutic targets for the prevention and treatment of the disease. PMID:24355226

Amedei, A; Codolo, G; Ozolins, D; Ballerini, C; Biagioli, T; Jaunalksne, I; Zilevica, A; D Elios, S; De Bernard, M; D' Elios, M M

2013-01-01

242

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

PubMed Central

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

Cabral, Agustina; Fernandez, Gimena; Perello, Mario

2013-01-01

243

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

PubMed Central

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

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

244

Cerebrospinal fluid glutamate concentration correlates with impulsive aggression in human subjects  

PubMed Central

Neurochemical studies have pointed to a modulatory role in human aggression for various central neurotransmitters. Some (e.g., serotonin) appear to play an inhibitory role, while others appear to play a facilitator role. While recent animal studies of glutaminergic activity suggest a facilitator role for central glutamate in the modulation of aggression, no human studies of central glutaminergic indices have yet been reported regarding aggression. Basal lumbar cerebrospinal fluid (CSF) was obtained from 38 physically healthy subjects with DSM-IV Personality Disorder (PD: n = 28) and from Healthy Volunteers (HV: n = 10) and assayed for glutamate, and other neurotransmitters, in CSF and correlated with measures of aggression and impulsivity. CSF Glutamate levels did not differ between the PD and HC subjects but did directly correlate with composite measures of both aggression and impulsivity and a composite measure of impulsive aggression in both groups. These data suggest a positive relationship between CSF Glutamate levels and measures of impulsive aggression in human subjects. Thus, glutamate function may contribute to the complex central neuromodulation of impulsive aggression in human subjects. PMID:23791397

Coccaro, Emil F.; Lee, Royce; Vezina, Paul

2014-01-01

245

Detection of disease-associated ?-synuclein in the cerebrospinal fluid: a feasibility study.  

PubMed

With the aim to evaluate the significance and reliability of detecting disease-specific ?-synuclein in the cerebrospinal fluid (CSF) we developed an ELISA and bead-assay. We used a commercial antibody (5G4) that does not bind to the physiological monomeric form of ?-synuclein, but is highly specific for the disease-associated forms, including high molecular weight fraction of ?-sheet rich oligomers. We applied both tests in CSF from a series of neuropathologically confirmed ?-synucleinopathy cases, including Parkinson' disease dementia (PDD) and dementia with Lewy bodies (DLB) (n = 7), as well as Alzheimer' disease (n = 6), and control patients without neurodegenerative pathologies (n = 9). Disease-specific ?-synuclein was detectable in the CSF in a subset of patients with ?-synuclein pathology in the brain. When combined with the analysis of total ?-synuclein, the bead-assay for disease-specific ?-synuclein was highly specific for PDD/DLB. Detection of disease-associated ?synuclein combined with the total levels of ?-synuclein is a promising tool for the in-vivo diagnosis of ?-synucleinopathies, including PDD and LBD. PMID:25131945

Unterberger, Ursula; Lachmann, Ingolf; Voigtländer, Till; Pirker, Walter; Berghoff, Anna S; Flach, Katharina; Wagner, Uta; Geneste, Aline; Perret-Liaudet, Armand; Kovacs, Gabor G

2014-01-01

246

Detection of disease-associated ?-synuclein in the cerebrospinal fluid: a feasibility study  

PubMed Central

With the aim to evaluate the significance and reliability of detecting disease-specific ?-synuclein in the cerebrospinal fluid (CSF) we developed an ELISA and bead-assay. We used a commercial antibody (5G4) that does not bind to the physiological monomeric form of ?-synuclein, but is highly specific for the disease-associated forms, including high molecular weight fraction of ?-sheet rich oligomers. We applied both tests in CSF from a series of neuropathologically confirmed ?-synucleinopathy cases, including Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB) (n = 7), as well as Alzheimer’s disease (n = 6), and control patients without neurodegenerative pathologies (n = 9). Disease-specific ?-synuclein was detectable in the CSF in a subset of patients with ?-synuclein pathology in the brain. When combined with the analysis of total ?-synuclein, the bead-assay for disease-specific ?-synuclein was highly specific for PDD/DLB. Detection of disease-associated ?-synuclein combined with the total levels of ?-synuclein is a promising tool for the in-vivo diagnosis of ?-synucleinopathies, including PDD and LBD. PMID:25131945

Unterberger, Ursula; Lachmann, Ingolf; Voigtländer, Till; Pirker, Walter; Berghoff, Anna S.; Flach, Katharina; Wagner, Uta; Geneste, Aline; Perret-Liaudet, Armand; Kovacs, Gabor G.

2014-01-01

247

High apolipoprotein E in cerebrospinal fluid of patients with Lewy body disorders is associated with dementia.  

PubMed

Apolipoprotein E ?4 allele (APOE ?4) increases the apolipoprotein E (apoE) protein levels in Alzheimer's disease (AD) cerebrospinal fluid (CSF). Thus, we hypothesized that apoE levels were also associated with the APOE genotype, and amyloid-? (A?)-associated clinical, functional, and imaging parameters in patients with Lewy body-associated disorders (LBD). Indeed, similar to AD, patients with LBD displayed high CSF apoE levels (greatest in patients with dementia with LBD), and this was linked to APOE ?4. High CSF apoE protein correlated positively with CSF soluble amyloid precursor protein, total tau, and cortical and striatal Pittsburgh compound B retention; and correlated negatively with CSF A?42, cognitive tests scores, and glucose uptake ratio in the temporal and parietal cortices. APOE ?4-triggered accumulation of apoE in CSF is related to A?-associated clinical and functional imaging parameters in LBD. Accordingly, therapeutic strategies aimed at reducing apoE levels in the brain should be explored not only in AD but also in LBD, particularly when accompanied with dementia. PMID:23978325

Vijayaraghavan, Swetha; Maetzler, Walter; Reimold, Matthias; Lithner, Christina Unger; Liepelt-Scarfone, Inga; Berg, Daniela; Darreh-Shori, Taher

2014-09-01

248

Small Molecules Present in the Cerebrospinal Fluid Metabolome Influence Superoxide Dismutase 1 Aggregation  

PubMed Central

Superoxide dismutase 1 (SOD1) aggregation is one of the pathological markers of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. The underlying molecular grounds of SOD1 pathologic aggregation remains obscure as mutations alone are not exclusively the cause for the formation of protein inclusions. Thus, other components in the cell environment likely play a key role in triggering SOD1 toxic aggregation in ALS. Recently, it was found that ALS patients present a specific altered metabolomic profile in the cerebrospinal fluid (CSF) where SOD1 is also present and potentially interacts with metabolites. Here we have investigated how some of these small molecules affect apoSOD1 structure and aggregation propensity. Our results show that as co-solvents, the tested small molecules do not affect apoSOD1 thermal stability but do influence its tertiary interactions and dynamics, as evidenced by combined biophysical analysis and proteolytic susceptibility. Moreover, these compounds influence apoSOD1 aggregation, decreasing nucleation time and promoting the formation of larger and less soluble aggregates, and in some cases polymeric assemblies apparently composed by spherical species resembling the soluble native protein. We conclude that some components of the ALS metabolome that shape the chemical environment in the CSF may influence apoSOD1 conformers and aggregation. PMID:24048249

Cristóvão, Joana S.; Leal, Sónia S.; Cardoso, Isabel; Gomes, Cláudio M.

2013-01-01

249

Prion-Seeding Activity in Cerebrospinal Fluid of Deer with Chronic Wasting Disease  

PubMed Central

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 (PrPd) 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 PrPd 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 PrPd 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

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

2013-01-01

250

Insights into pediatric diffuse intrinsic pontine glioma through proteomic analysis of cerebrospinal fluid.  

PubMed

Diffuse intrinsic pontine glioma (DIPG) is a leading cause of brain tumor-related death in children. DIPG is not surgically resectable, resulting in a paucity of tissue available for molecular studies. As such, tumor biology is poorly understood, and, currently, there are no effective treatments. In the absence of frozen tumor specimens, body fluids--such as cerebrospinal fluid (CSF), serum, and urine--can serve as more readily accessible vehicles for detecting tumor-secreted proteins. We analyzed a total of 76 specimens, including CSF, serum, urine, and normal and tumor brainstem tissue. Protein profiling of CSF from patients with DIPG was generated by mass spectrometry using an LTQ-Orbitrap-XL and database search using the Sequest algorithm. Quantitative and statistical analyses were performed with ProteoIQ and Partek Genomics Suite. A total of 528 unique proteins were identified, 71% of which are known secreted proteins. CSF proteomic analysis revealed selective upregulation of Cyclophillin A (CypA) and dimethylarginase 1 (DDAH1) in DIPG (n = 10), compared with controls (n = 4). Protein expression was further validated with Western blot analysis and immunohistochemical assays using CSF, brain tissue, serum, and urine from DIPG and control specimens. Immunohistochemical staining showed selective upregulation of secreted but not cytosolic CypA and DDAH1 in patients with DIPG. In this study, we present the first comprehensive protein profile of CSF specimens from patients with DIPG to demonstrate selective expression of tumor proteins potentially involved in brainstem gliomagenesis. Detection of secreted CypA and DDAH1 in serum and urine has potential clinical application, with implications for assessing treatment response and detecting tumor recurrence in patients with DIPG. PMID:22492959

Saratsis, Amanda M; Yadavilli, Sridevi; Magge, Suresh; Rood, Brian R; Perez, Jennifer; Hill, D Ashley; Hwang, Eugene; Kilburn, Lindsay; Packer, Roger J; Nazarian, Javad

2012-05-01

251

Insights into pediatric diffuse intrinsic pontine glioma through proteomic analysis of cerebrospinal fluid  

PubMed Central

Diffuse intrinsic pontine glioma (DIPG) is a leading cause of brain tumor–related death in children. DIPG is not surgically resectable, resulting in a paucity of tissue available for molecular studies. As such, tumor biology is poorly understood, and, currently, there are no effective treatments. In the absence of frozen tumor specimens, body fluids—such as cerebrospinal fluid (CSF), serum, and urine—can serve as more readily accessible vehicles for detecting tumor-secreted proteins. We analyzed a total of 76 specimens, including CSF, serum, urine, and normal and tumor brainstem tissue. Protein profiling of CSF from patients with DIPG was generated by mass spectrometry using an LTQ-Orbitrap-XL and database search using the Sequest algorithm. Quantitative and statistical analyses were performed with ProteoIQ and Partek Genomics Suite. A total of 528 unique proteins were identified, 71% of which are known secreted proteins. CSF proteomic analysis revealed selective upregulation of Cyclophillin A (CypA) and dimethylarginase 1 (DDAH1) in DIPG (n = 10), compared with controls (n = 4). Protein expression was further validated with Western blot analysis and immunohistochemical assays using CSF, brain tissue, serum, and urine from DIPG and control specimens. Immunohistochemical staining showed selective upregulation of secreted but not cytosolic CypA and DDAH1 in patients with DIPG. In this study, we present the first comprehensive protein profile of CSF specimens from patients with DIPG to demonstrate selective expression of tumor proteins potentially involved in brainstem gliomagenesis. Detection of secreted CypA and DDAH1 in serum and urine has potential clinical application, with implications for assessing treatment response and detecting tumor recurrence in patients with DIPG. PMID:22492959

M. Saratsis, Amanda; Yadavilli, Sridevi; Magge, Suresh; Rood, Brian R.; Perez, Jennifer; Hill, D. Ashley; Hwang, Eugene; Kilburn, Lindsay; Packer, Roger J.; Nazarian, Javad

2012-01-01

252

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

PubMed Central

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

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

2013-01-01

253

Potential for intranasal drug delivery to alter cerebrospinal fluid outflow via the nasal turbinate lymphatics  

PubMed Central

Background Cerebrospinal fluid absorption (CSF) at the cribriform plate is mediated by direct extracranial connections to the lymphatic system. Given the accessibility of these pharmacologically responsive vessels we hypothesized that the rate of CSF outflow can be modulated via the intranasal delivery of drugs known to affect lymphatic contractile activity. Findings Fluid was infused into the lateral ventricle of anesthetized sheep and inflow rate and CSF pressure measured during intranasal administration of pharmacological agents. CSF absorption was calculated at steady-state CSF pressures. The ability of a pharmacological agent to alter CSF absorption was related to the steady-state intracranial pressure (ICP), the concentration and the class of pharmacological agent delivered. An increase in drug concentration correlated with an increase in CSF absorption at high ICP (45 cm H2O, r?=?0.42, p?=?0.0058). Specifically, the delivery of NG-monomethyl L-arginine (L-NMMA) significantly increased CSF absorption by 2.29 fold over no treatment (2.29?±?0.34 mL/min), while the thromboxane A2 analogue U46619 resulted in a 2.44 fold increase in CSF absorption over no treatment (2.44?±?0.55 mL/min). Saline delivery did not significantly increase CSF absorption (0.88?±?0.097 mL/min). A trend of increased CSF absorption upon noradrenaline delivery was observed: however, this did not reach statistical significance. Increasing drug concentrations inversely correlated with CSF outflow resistance across all drug classes (r?=?-0.26, p?=?0.046). Conclusions The administration of nebulized pharmacological agents intranasally has the potential to provide an alternate method to non-invasively modulate CSF absorption and outflow resistance. PMID:24528926

2014-01-01

254

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

PubMed Central

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

2013-01-01

255

Detection of Circulating gp43 Antigen in Serum, Cerebrospinal Fluid, and Bronchoalveolar Lavage Fluid of Patients with Paracoccidioidomycosis  

PubMed Central

Paracoccidioidomycosis (PCM) is an important systemic fungal disease, particularly among individuals living and working in rural areas of endemicity in Latin America, who, without antifungal therapy, may develop fatal acute or chronic infection. For such patients, the detection of antibody responses by immunodiffusion is of limited value due to false-negative results. In contrast, the detection of Paracoccidioides brasiliensis gp43 circulating antigen may represent a more practical approach to the rapid diagnosis of the disease. Accordingly, an inhibition enzyme-linked immunosorbent assay (inh-ELISA) was developed for the detection of a 43-kDa P. brasiliensis-specific epitope incorporating a species-specific murine monoclonal antibody. With sera from patients with acute and chronic forms of the disease (n = 81), the overall sensitivity of the test was found to be 95.1%, while specificity was found to be 97.5% compared to that with normal human sera from blood donors (n = 93) and sera from patients with other chronic fungal infections (histoplasmosis [n = 33] and cryptococcosis [n = 20]). The inh-ELISA detected circulating antigen in 100% of patients with the acute form of PCM and in 95.31 and 100% of patients with the chronic multifocal and unifocal forms of PCM according to the patient's clinical presentation. Cerebrospinal fluid from 14 patients with neuroparacoccidioidomycosis and 13 samples of bronchoalveolar lavage fluid from patients with pulmonary unifocal PCM were also tested for gp43 detection, with the test showing 100% sensitivity and specificity. This novel, highly specific inh-ELISA represents a significant addition to the existing tests for the diagnosis of PCM. PMID:12904374

Marques da Silva, Silvia Helena; Colombo, Arnaldo Lopes; Blotta, Maria Heloisa Souza Lima; Lopes, José Daniel; Queiroz-Telles, Flávio; Pires de Camargo, Zoilo

2003-01-01

256

Visualisation of cerebrospinal fluid flow patterns in albino Xenopus larvae in vivo  

PubMed Central

Background It has long been known that cerebrospinal fluid (CSF), its composition and flow, play an important part in normal brain development, and ependymal cell ciliary beating as a possible driver of CSF flow has previously been studied in mammalian fetuses in vitro. Lower vertebrate animals are potential models for analysis of CSF flow during development because they are oviparous. Albino Xenopus laevis larvae are nearly transparent and have a straight, translucent brain that facilitates the observation of fluid flow within the ventricles. The aim of these experiments was to study CSF flow and circulation in vivo in the developing brain of living embryos, larvae and tadpoles of Xenopus laevis using a microinjection technique. Methods The development of Xenopus larval brain ventricles and the patterns of CSF flow were visualised after injection of quantum dot nanocrystals and polystyrene beads (3.1 or 5.8 ?m in diameter) into the fourth cerebral ventricle at embryonic/larval stages 30-53. Results The fluorescent nanocrystals showed the normal development of the cerebral ventricles from embryonic/larval stages 38 to 53. The polystyrene beads injected into stage 47-49 larvae revealed three CSF flow patterns, left-handed, right-handed and non-biased, in movement of the beads into the third ventricle from the cerebral aqueduct (aqueduct of Sylvius). In the lateral ventricles, anterior to the third ventricle, CSF flow moved anteriorly along the outer wall of the ventricle to the inner wall and then posteriorly, creating a semicircle. In the cerebral aqueduct, connecting the third and fourth cerebral ventricles, CSF flow moved rostrally in the dorsal region and caudally in the ventral region. Also in the fourth ventricle, clear dorso-ventral differences in fluid flow pattern were observed. Conclusions This is the first visualisation of the orchestrated CSF flow pattern in developing vertebrates using a live animal imaging approach. CSF flow in Xenopus albino larvae showed a largely consistent pattern, with the exception of individual differences in left-right asymmetrical flow in the third ventricle. PMID:22534239

2012-01-01

257

Analytical solution for pulsatile viscous flow in a straight elliptic annulus and application to the motion of the cerebrospinal fluid  

NASA Astrophysics Data System (ADS)

We present here the analytical solution of transient, laminar, viscous flow of an incompressible, Newtonian fluid driven by a harmonically oscillating pressure gradient in a straight elliptic annulus. The analytical formulation is based on the exact solution of the governing fluid flow equations known as Navier-Stokes equations. We validate the analytical solution using a finite-volume computational fluid dynamics approach. As the analytical solution includes Mathieu and modified Mathieu functions, we also present a stepwise procedure for their evaluation for large complex arguments typically associated with viscous flows. We further outline the procedure for evaluating the associated Fourier coefficients and their eigenvalues. We finally apply the analytical solution to investigate the cerebrospinal fluid flow in the human spinal cavity, which features a shape similar to an elliptic annulus.

Gupta, Sumeet; Poulikakos, Dimos; Kurtcuoglu, Vartan

2008-09-01

258

Analysis of Risk Factors and Management of Cerebrospinal Fluid Morbidity in the Treatment of Spinal Dysraphism  

PubMed Central

Objective Spinal dysraphism defects span wide spectrum. Wound dehiscence is a common postoperative complication, and is a challenge in the current management of cerebrospinal fluid (CSF) leaks and wound healing. The purpose of this study is to evaluate the risks of CSF-related morbidity in the surgical treatment of spinal dysraphism. Methods Ten patients with spinal dysraphism were included in this retrospective study. The median age of the cohort was 4.8 months. To assess the risk of CSF morbidity, we measured the skin lesion area and the percentage of the skin lesion area relative to the back surface for each patient. We then analyzed the relationship between morbidity and the measured skin lesion area or related factors. Results The overall median skin lesion area was 36.2 cm2 (n=10). The percentage of the skin lesion area relative to the back surface ranged from 0.6% to 18.1%. During surgical reconstruction, 4 patients required subsequent operations to repair CSF morbidity. The comparison of the mean area of skin lesions between the CSF morbidity group and the non-CSF morbidity group was statistically significant (average volume skin lesion of 64.4±32.5 cm2 versus 27.7±27.8 cm2, p<0.05). CSF morbidity tended to occur either when the skin lesion area was up to 44.2 cm2 or there was preexisting fibrosis before revision with an accompanying broad-based dural defect. Conclusion Measuring the lesion area, including the skin, dura, and related surgical parameters, offers useful information for predicting wound challenges and selecting appropriate reconstructive surgery methods. PMID:24278652

Lee, Byung-Jou; Han, Seong-Rok; Choi, Chan-Young; Lee, Dong-Joon; Kang, Jae Heon

2013-01-01

259

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

PubMed Central

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 also were identified in the CSFs of 1 of 20 individuals with chronic schizophrenia. However, retroviral sequences were not identified in any of the CSFs obtained from 22 individuals with noninflammatory neurological diseases or from 30 individuals without evidence of neurological or psychiatric diseases (?2 = 19.25, P < 0.001). The nucleotide sequences identified in the CSFs of the individuals with schizophrenia or schizoaffective disorder were related to those of the human endogenous retroviral (HERV)-W family of endogenous retroviruses and to other retroviruses in the murine leukemia virus genus. Transcription of RNA homologous to members of the HERV-W family of retroviruses also was found to be up-regulated differentially in the frontal cortex regions of brains obtained postmortem from individuals with schizophrenia, as compared with corresponding tissue from individuals without psychiatric diseases. The transcriptional activation of certain retroviral elements within the central nervous system may be associated with the development of schizophrenia in at least some individuals. The further characterization of retroviral elements within the central nervous system of individuals with schizophrenia might lead to improved methods for the diagnosis and management of this disorder. PMID:11296294

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

2001-01-01

260

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

PubMed

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 also were identified in the CSFs of 1 of 20 individuals with chronic schizophrenia. However, retroviral sequences were not identified in any of the CSFs obtained from 22 individuals with noninflammatory neurological diseases or from 30 individuals without evidence of neurological or psychiatric diseases (chi(2) = 19.25, P < 0.001). The nucleotide sequences identified in the CSFs of the individuals with schizophrenia or schizoaffective disorder were related to those of the human endogenous retroviral (HERV)-W family of endogenous retroviruses and to other retroviruses in the murine leukemia virus genus. Transcription of RNA homologous to members of the HERV-W family of retroviruses also was found to be up-regulated differentially in the frontal cortex regions of brains obtained postmortem from individuals with schizophrenia, as compared with corresponding tissue from individuals without psychiatric diseases. The transcriptional activation of certain retroviral elements within the central nervous system may be associated with the development of schizophrenia in at least some individuals. The further characterization of retroviral elements within the central nervous system of individuals with schizophrenia might lead to improved methods for the diagnosis and management of this disorder. PMID:11296294

Karlsson, H; Bachmann, S; Schröder, J; McArthur, J; Torrey, E F; Yolken, R H

2001-04-10

261

Cerebrospinal fluid inflammatory markers in patients with multiple sclerosis: a pilot study.  

PubMed

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Autoimmune inflammation is common in the early stages of MS. This stage is followed by the neurodegenerative process. The result of these changes is axon and myelin breakdown. Although MS is according to McDonald's revised diagnostic criteria primarily a clinical diagnosis, paraclinical investigation methods are an important part in the diagnosis of MS. In common practice, magnetic resonance imaging of the brain and spinal cord, examination of cerebrospinal fluid (CSF) and examination of visual evoked potentials are used. There are an increasing number of studies dealing with biomarkers in CSF and their role in the diagnosis and treatment of MS. We hypothesized that the levels of some markers could be changed in MS in comparison with controls. We studied five inflammatory markers [interleukin-6 (IL-6), interleukin-8, interleukin-10 (IL-10), beta-2-microglobulin, orosomucoid]. CSF and serum levels of inflammatory markers were assessed in 38 patients with newly diagnosed MS meeting McDonald's revised diagnostic criteria and in 28 subjects as a control group (CG). Levels of beta-2-microglobulin and interleukin-8 in CSF were found to be significantly higher in MS patients in comparison to CG (p < 0.001 resp. p = 0.007). No differences in other CSF markers (IL-6, IL-10 and orosomucoid) and serum levels of all markers between both groups were found. The levels of two studied inflammatory markers were found to be increased at the time of first clinical symptoms of MS. Research on the role of inflammatory and neurodegenerative markers in MS should continue. PMID:24894698

Matej?íková, Z; Mareš, J; P?ikrylová Vranová, H; Klosová, J; Sládková, V; Doláková, J; Zapletalová, J; Ka?ovský, P

2015-02-01

262

Idiopathic Normal Pressure Hydrocephalus has a Different Cerebrospinal Fluid Biomarker Profile from Alzheimer's Disease.  

PubMed

The diagnosis of idiopathic normal pressure hydrocephalus (iNPH) is sometimes complicated by concomitant Alzheimer's disease (AD) pathology. The purpose of the present study is to identify an iNPH-specific cerebrospinal fluid (CSF) biomarker dynamics and to assess its ability to differentiate iNPH from AD. Total tau (t-tau), tau phosphorylated at threonine 181 (p-tau), amyloid-? (A?) 42 and 40, and leucine-rich ?-2-glycoprotein (LRG) were measured in 93 consecutive CSF samples consisting of 55 iNPH (46 tap test responders), 20 AD, 11 corticobasal syndrome, and 7 spinocerebeller disease. Levels of t-tau and p-tau were significantly decreased in iNPH patients especially in tap test responders compared to AD. Correlation was observed between Mini-Mental State Examination scores and A?42 in AD (R = 0.44) and mildly in iNPH (R = 0.28). Although A?42/40 ratio showed no significant difference between iNPH and AD (p = 0.08), the levels of A?40 and A?42 correlated positively with each other in iNPH (R = 0.73) but much less in AD (R = 0.26), suggesting that they have discrete amyloid clearance and pathology. LRG levels did not differ between the two. Thus, our study shows that although CSF biomarkers of iNPH patients can be affected by concomitant tau and/or amyloid pathology, CSF t-tau and p-tau are highly useful for differentiation of iNPH and AD. PMID:25428256

Jingami, Naoto; Uemura, Kengo; Noto, Rio; Asada, Megumi; Takahashi, Makio; Ozaki, Akihiko; Kihara, Takeshi; Kageyama, Takashi; Takahashi, Ryosuke; Shimohama, Shun; Kinoshita, Ayae

2014-11-25

263

Alterations of endocannabinoids in cerebrospinal fluid of dogs with epileptic seizure disorder  

PubMed Central

Background Epilepsy is one of the most common chronic neurological disorders in dogs characterized by recurrent seizures. The endocannabinoid (EC) system plays a central role in suppressing pathologic neuronal excitability and in controlling the spread of activity in an epileptic network. Endocannabinoids are released on demand and their dysregulation has been described in several pathological conditions. Recurrent seizures may lead to an adverse reorganization of the EC system and impairment of its protective effect. In the current study, we tested the hypothesis that cerebrospinal fluid (CSF) concentrations of the endocannabinoids anandamide (AEA) and 2-arachidonoyl glycerol (2AG) are altered in epileptic dogs. Concentrations of AEA and total AG (sum of 2AG and 1AG) were measured in 40 dogs with idiopathic epilepsy and in 16 unaffected, healthy control dogs using liquid chromatography combined with tandem mass spectrometry. Results AEA and total AG were measured at 4.94 (3.18 – 9.17) pM and 1.43 (0.90 – 1.92) nM in epileptic dogs and at 3.19 (2.04 – 4.28) pM and 1.76 (1.08 – 2.69) nM in the control group, respectively (median, 25 – 75% percentiles in brackets). The AEA difference between epileptic and healthy dogs was statistically significant (p

2013-01-01

264

Cerebrospinal-fluid orexin levels and daytime somnolence in frontotemporal dementia.  

PubMed

Daytime somnolence and sleep-wake cycle disturbances are commonly encountered symptoms in Frontotemporal Dementia (FTD). Orexin-A (Hypocretin-1) is a hypothalamic neuropeptide regulating the sleep-wake rhythm. We investigated the cerebrospinal-fluid (CSF) orexin levels in a population of FTD patients and evaluated whether there is a relationship between daytime somnolence and CSF orexin concentrations. CSF orexin levels were measured in a sample of FTD patients (n = 11) compared to a population of non-demented controls (n = 13) similar for age and sex. Moreover, CSF orexin concentrations were correlated with daytime somnolence investigated by means of the Epworth Sleepiness Scale (ESS) in both FTD patients and controls. FTD patients showed CSF orexin concentrations (164.3 ± 66.45 vs 170.81 ± 42.73 pg/mL) and ESS scores (7.45 ± 4.36 vs 3.84 ± 1.82) not different from controls. However, three FTD patients showed pathological daytime sleepiness (ESS > 10) coupled with the lowest CSF orexin levels. In addition, we found a significant negative correlation between CSF orexin levels and ESS scores in the FTD population (R = -0.91; p < 0.0001), which was not evident in the control group (R = 0.16; p > 0.05). This is the first study investigating CSF orexin concentrations in FTD. We did not find differences in CSF orexin concentrations between FTD patients and controls. However, a significant negative correlation between daytime somnolence and CSF orexin levels was evident in FTD patients. Moreover, we have found that pathological daytime somnolence was evident in those FTD patients with the lowest CSF orexin levels. Based on these findings, we argued that lower orexin levels may be permissive for increased daytime somnolence in FTD. PMID:25119837

Liguori, C; Romigi, A; Mercuri, N B; Nuccetelli, M; Izzi, F; Albanese, M; Sancesario, G; Martorana, A; Sancesario, G M; Bernardini, S; Marciani, M G; Placidi, F

2014-09-01

265

Disposition and Elimination of Meropenem in Cerebrospinal Fluid of Hydrocephalic Patients with External Ventriculostomy  

PubMed Central

The broad antibacterial spectrum and the low incidence of seizures in meropenem-treated patients qualifies meropenem for therapy of bacterial meningitis. The present study evaluates concentrations in ventricular cerebrospinal fluid (CSF) in the absence of pronounced meningeal inflammation. Patients with occlusive hydrocephalus caused by cerebrovascular diseases, who had undergone external ventriculostomy (n = 10, age range 48 to 75 years), received 2 g of meropenem intravenously over 30 min. Serum and CSF were drawn repeatedly and analyzed by liquid chromatography-mass spectroscopy. Pharmacokinetics were determined by noncompartmental analysis. Maximum concentrations in serum were 84.7 ± 23.7 ?g/ml. A CSF maximum (CmaxCSF) of 0.63 ± 0.50 ?g/ml (mean ± standard deviation) was observed 4.1 ± 2.6 h after the end of the infusion. CmaxCSF and the area under the curve for CSF (AUCCSF) depended on the AUC for serum (AUCS), the CSF-to-serum albumin ratio, and the CSF leukocyte count. Elimination from CSF was considerably slower than from serum (half-life at ? phase [t1/2?] of 7.36 ± 2.89 h in CSF versus t1/2? of 1.69 ± 0.60 h in serum). The AUCCSF/AUCS ratio for meropenem, as a measure of overall CSF penetration, was 0.047 ± 0.022. The AUCCSF/AUCS ratio for meropenem was similar to that for other ?-lactam antibiotics with a low binding to serum proteins. The concentration maxima of meropenem in ventricular CSF observed in this study are high enough to kill fully susceptible pathogens. They may not be sufficient to kill bacteria with a reduced sensitivity to carbapenems, although clinical success has been reported for patients with meningitis caused by penicillin-resistant pneumococci and Pseudomonas aeruginosa. PMID:9687399

Nau, Roland; Lassek, Christoph; Kinzig-Schippers, Martina; Thiel, Andreas; Prange, Hilmar W.; Sörgel, Fritz

1998-01-01

266

Cerebrospinal fluid and plasma oxytocin concentrations are positively correlated and negatively predict anxiety in children.  

PubMed

The neuropeptide oxytocin (OXT) exerts anxiolytic and prosocial effects in the central nervous system of rodents. A number of recent studies have attempted to translate these findings by investigating the relationships between peripheral (e.g., blood, urinary and salivary) OXT concentrations and behavioral functioning in humans. Although peripheral samples are easy to obtain in humans, whether peripheral OXT measures are functionally related to central OXT activity remains unclear. To investigate a possible relationship, we quantified OXT concentrations in concomitantly collected cerebrospinal fluid (CSF) and blood samples from child and adult patients undergoing clinically indicated lumbar punctures or other CSF-related procedures. Anxiety scores were obtained in a subset of child participants whose parents completed psychometric assessments. Findings from this study indicate that plasma OXT concentrations significantly and positively predict CSF OXT concentrations (r=0.56, P=0.0064, N=27). Moreover, both plasma (r=-0.92, P=0.0262, N=10) and CSF (r=-0.91, P=0.0335, N=10) OXT concentrations significantly and negatively predicted trait anxiety scores, consistent with the preclinical literature. Importantly, plasma OXT concentrations significantly and positively (r=0.96, P=0.0115, N=10) predicted CSF OXT concentrations in the subset of child participants who provided behavioral data. This study provides the first empirical support for the use of blood measures of OXT as a surrogate for central OXT activity, validated in the context of behavioral functioning. These preliminary findings also suggest that impaired OXT signaling may be a biomarker of anxiety in humans, and a potential target for therapeutic development in individuals with anxiety disorders.Molecular Psychiatry advance online publication, 4 November 2014; doi:10.1038/mp.2014.132. PMID:25349162

Carson, D S; Berquist, S W; Trujillo, T H; Garner, J P; Hannah, S L; Hyde, S A; Sumiyoshi, R D; Jackson, L P; Moss, J K; Strehlow, M C; Cheshier, S H; Partap, S; Hardan, A Y; Parker, K J

2014-11-01

267

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

PubMed

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

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

2014-11-01

268

Inhibition of penicillin transport from the cerebrospinal fluid after intracisternal inoculation of bacteria.  

PubMed

The effect of intracisternal inoculation of bacteria on the choroid plexus system, which transports penicillin from cerebrospinal fluid (CSF) to blood, was studied in vitro and in vivo. Meningeal and choroid plexus inflammations as well as CSF pleocytosis were induced in rabbits with intracisternal inoculations of Hemophilus influenzae or Staphylococcus aureus. At various times after bacterial inoculation, the choroid plexuses of the inoculated rabbits were removed and incubated in artificial CSF containing [(14)C]penicillin. The ability of the choroid plexuses to accumulate pencillin in vitro was measured and was found to be depressed as compared with controls. This depression of choroid plexus uptake reversed with resolution of the inflammatory process. In vivo on the day after intracisternal inoculation of Hemophilus influenzae, a decrease in the disappearance of penicillin relative to inulin in the inoculated rabbits (as compared to the controls) was observed when [(14)C]penicillin and [(3)H]inulin were injected intraventricularly and cisternal CSF was sampled 2 h later. This decrease could not be explained by penicillin binding to the CSF exudate. However, the choroid plexus transport system for penicillin was only partially depressed in those inoculated rabbits with bacterially induced inflammation, since in vitro the choroid plexuses could still accumulate penicillin and in vivo CSF penicillin levels could be further increased with probenecid pretreatment. These results suggest that CSF penicillin levels are increased in this model due to three factors: a depression of active efflux of penicillin from the CSF, an increase in permeability to penicillin of inflamed meninges, and, less significantly, by CSF binding of penicillin. PMID:4546548

Spector, R; Lorenzo, A V

1974-08-01

269

Non-neurological surgery and cerebrospinal fluid biomarkers for neuronal and astroglial integrity.  

PubMed

Non-neurological surgery has both acute and long-term effects on the brain. Markers for Alzheimer pathology may be used to study surgically induced neurological changes relevant for postoperative confusion, asthenia or cognitive decline. Inflammatory biomarkers, total tau (T-tau) and phosphorylated tau (P-tau) were recently shown to increase progressively in the cerebrospinal fluid (CSF) during surgery for nasal CSF leak, suggesting a neuroinflammatory response with signs of neuronal damage. We used a study group of 35 patients, undergoing knee arthroplasty with a spinal blockade and propofol sedation, to replicate this finding. Five CSF biomarkers were analyzed before, 3 h after and on the morning after the interventions: T-tau and P-tau for cortical axonal integrity and tangle pathology, respectively, the 42 amino acids form of amyloid ? (A?42) for plaque formation, neurofilament light (NFL) for the integrity of large-caliber myelinated axons and glial fibrillary acidic protein (GFAp) for astroglial cell integrity. CSF T-tau concentrations increased significantly during and after surgery (p = 0.028) and were significantly correlated with the administered doses of bupivacaine. P-tau, A?42 and NFL remained unchanged, while the mean GFAp concentration increased with a large standard deviation. CSF T-tau and P-tau correlated significantly with the CSF/serum albumin ratios as an indicator of blood-brain barrier permeability. Findings from earlier studies showing a significant increase in biomarkers for Alzheimer's pathology during surgery were partly replicated, as neurochemical signs of impaired cortical axonal integrity during non-neurological surgery were detected. Bupivacaine may be involved in these reactions. PMID:24420082

Anckarsäter, Rolf; Anckarsäter, Henrik; Bromander, Sara; Blennow, Kaj; Wass, Caroline; Zetterberg, Henrik

2014-06-01

270

Diagnostic utility of cerebrospinal fluid flow cytometry in patients with and without prior hematologic malignancy.  

PubMed

Flow cytometry (FCM) is an adjunct study to routine analysis of cerebrospinal fluid (CSF) to investigate for involvement by a hematologic malignancy. However, in our experience, FCM only infrequently detects abnormalities in CSF. To help optimize resources without forfeiting clinically important data, we sought to determine evidence-based indications and criteria for performing FCM on CSF. FCM results of 316 consecutive CSF specimens were retrospectively reviewed and correlated with clinical history, total nucleated cell (TNC) counts, and results of concurrent cytologic review. Of 255 samples adequate for analysis, 54% were from patients with a prior history of hematologic malignancy, of which 12% (17 cases) were abnormal by FCM. Corresponding TNC counts among samples with abnormal FCM ranged from 0-1050 cells/µL, and only 44% showed abnormal morphology on concurrent cytology. Of the remaining 46% of samples from patients with no known history of hematologic malignancy who had CSF sampling for neurological indications, only one (1%) was abnormal by FCM. This specimen had an elevated TNC count (39 cells/µL) but lacked clearly abnormal findings on concurrent cytology. These results support the use of CSF FCM only in patients with a history of hematologic malignancy or, in the absence of such a history, in samples showing pleocytosis. If these criteria were applied to the current cohort using a TNC count cut-off of >5 cells/µL, 23% of samples would have been deferred from testing, resulting in decreased cost, improved efficiency, and reduction in the need for unnecessary testing without a negative impact on clinical care. PMID:25042070

Kovach, Alexandra E; DeLelys, Michelle E; Kelliher, Abigail S; Dillon, Laura J; Hasserjian, Robert P; Ferry, Judith A; Preffer, Frederic I; Sohani, Aliyah R

2014-10-01

271

Performance of laser bonded glass/polyimide microjoints in cerebrospinal fluid.  

PubMed

In this paper, laser bonded microjoints between glass and polyimide is considered to examine their potential applicability in encapsulating neural implants. To facilitate bonding between polyimide and glass, a thin titanium film with a thickness of 2 microm was deposited on borosilicate glass plates by a physical vapor deposition (PVD) process. Titanium coated glass was then joined with polyimide by using a cw fiber laser emitting at a wavelength of 1.1 microm (1.0 W) to prepare several tensile samples. Some of the samples were exposed to artificial cerebrospinal fluid (aCSF) at 37 degrees C for two weeks to assess long-term integrity of the joints. Both the as-received and aCSF soaked samples were subjected to uniaxial tensile loads for bond strengths measurements. The bond strengths for the as-received and aCSF soaked samples were measured to be 7.31 and 5.33 N/mm, respectively. Although the long-term exposure of the microjoints to aCSF has resulted in 26% reduction of bond strength, the samples still retain considerably high strength as compared with the titanium-polyimide samples. The failed glass/polyimide samples were also analyzed using optical microscopy, and failure mechanisms are discussed. In addition, a two dimensional finite element analysis (FEA) was conducted to understand the stress distribution within the substrate materials while the samples are in tension. The FEA results match reasonably well with the experimental load-displacement curves for as-received samples. Detailed discussion on various stress contours is presented in the paper, and the failure mechanisms observed from the experiment are shown in good agreement with the FEA predicted ones. PMID:17334691

Mian, A; Newaz, G; Georgiev, D G; Rahman, N; Vendra, L; Auner, G; Witte, R; Herfurth, H

2007-03-01

272

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

PubMed

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

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

2011-01-01

273

Endothelin-1 gene polymorphisms influence cerebrospinal fluid endothelin-1 levels following aneurysmal subarachnoid hemorrhage.  

PubMed

Aneurysmal subarachnoid hemorrhage is a type of stroke with high morbidity and mortality. Increased endothelin-1 (ET-1) levels have been associated with increased risk of cerebral vasospasm, which is associated with increased morbidity. The purpose of this study was to investigate the relationships between ET-1 genotypes and ET-1 protein levels in cerebrospinal fluid (CSF) measured 72 hr before angiographic vasospasm measurement in subjects at high risk of cerebral vasospasm. Specifically, this study evaluated the differences between variant positive and variant negative groups of nine different ET-1 single-nucleotide polymorphisms (SNPs) in relationship with the ET-1 protein exposure rate. The CSF ET-1 protein levels were quantified using enzyme-linked immunosorbent assay. One functional SNP and eight ET-1 tagging SNPs were selected because they represent genetic variability in the entire ET-1 gene. The variant negative group of SNP rs2070699 was associated with a significantly higher ET-1 exposure rate than the variant positive group (p = 0.004), while the variant positive group of the rs5370 group showed a trend toward association with a higher ET-1 exposure rate (p = 0.051). Other SNPs were not informative. This is the first study to show differences in ET-1 exposure rate 72 hr before angiography in relation to ET-1 genotypes. These exploratory findings need to be replicated in a larger study; if replicated, these differences in genotypes may be a way to inform clinicians of those patients at a higher risk of increased ET-1 protein levels, which may lead to a higher risk of angiographic vasospasm. PMID:24852947

Gallek, Matthew J; Alexander, Sheila A; Crago, Elizabeth; Sherwood, Paula R; Klamerus, Megan; Horowitz, Michael B; Poloyac, Samuel M; Conley, Yvette

2015-03-01

274

Proteomic Analysis of Cerebrospinal Fluid in Alzheimer's Disease: Wanted Dead or Alive.  

PubMed

Clinical diagnosis of Alzheimer's disease (AD) relying on symptomatic features has a low specificity, emphasizing the importance of the pragmatic use of neurochemical biomarkers. The most advanced and reliable markers are amyloid-? (A?42), total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) with relatively high levels of sensitivity, specificity, and diagnostic accuracy. Recent advances within the field of proteomics offer the potential to search for novel biomarkers in CSF by using modern methods, such as microarrays. The purpose of this study was to identify pathognostic proteins in CSF obtained from patients whose clinical AD diagnosis was confirmed by the "core" biomarkers. CSF samples were obtained from 25 AD patients and 25 control individuals. The levels of A?42, t-tau, and p-tau were measured by ELISA. In the microarray experiments, ultrasensitive slides representing of 653 antigens were used. Apolipoprotein E genotyping was also determined. A decrease of seven CSF proteins in AD were found, four of them (POLG, MGMT, parkin, and ApoD) have a protective function against neuronal death, while the remaining three proteins (PAR-4, granzyme B, Cdk5) trigger multiple pathways facilitating neuronal cell death. Since these proteins from CSF samples could not be identified by western blot, their decreased levels in AD patients were not verified. Our results provide new information of pathognostic importance of POLG and granzyme B in AD. Although the function of MGMT, parkin, ApoD, PAR-4, and Cdk5 was previously known in AD, the findings presented here provide novel evidence of the significance of CSF analysis in the mapping of the AD pathomechanism. PMID:25428253

Oláh, Zita; Kálmán, János; Tóth, Melinda E; Zvara, Agnes; Sántha, Miklós; Ivitz, Eszter; Janka, Zoltán; Pákáski, Magdolna

2014-11-25

275

Cerebrospinal fluid metabolomics reveals altered waste clearance and accelerated aging in HIV patients with neurocognitive impairment  

PubMed Central

Objective(s): HIV-associated neurocognitive disorders (HAND) remain prevalent in HIV-infected patients on antiretroviral therapy (ART), but the underlying mechanisms are unclear. Some features of HAND resemble those of age-associated cognitive decline in the absence of HIV, suggesting that overlapping mechanisms may contribute to neurocognitive impairment. Design: Cross-sectional analysis of cerebrospinal fluid (CSF) from 100 individuals (46 HIV-positive patients and 54 HIV-negative controls). Methods: Untargeted CSF metabolite profiling was performed using liquid/gas chromatography followed by mass spectrometry. Cytokine profiling was performed by Bioplex. Bioinformatic analyses were performed in Metaboanalyst and R. Results: Alterations in the CSF metabolome of HIV patients on ART mapped to pathways associated with neurotransmitter production, mitochondrial function, oxidative stress, and metabolic waste. Many CSF metabolites altered in HIV overlapped with those altered with advanced age in HIV-negative controls, suggesting a pattern indicative of accelerated aging. Machine learning models identified neurotransmitters (glutamate, N-acetylaspartate), markers of glial activation (myo-inositol), and ketone bodies (beta-hydroxybutyric acid, 1,2-propanediol) as top-ranked classifiers of HAND. These CSF metabolites correlated with worse neurocognitive test scores, plasma inflammatory biomarkers [interferon (IFN)-?, IFN-?, interleukin (IL)-8, IL-1?, IL-6, IL-2Ra], and intrathecal IFN responses (IFN-? and kynurenine : tryptophan ratio), suggesting inter-relationships between systemic and intrathecal inflammation and metabolic alterations in CSF. Conclusions: Alterations in the CSF metabolome of HIV patients on ART suggest that persistent inflammation, glial responses, glutamate neurotoxicity, and altered brain waste disposal systems contribute to mechanisms involved in HAND that may be augmented with aging. PMID:24752083

Cassol, Edana; Misra, Vikas; Dutta, Anupriya; Morgello, Susan; Gabuzda, Dana

2014-01-01

276

Elevated levels of cerebrospinal fluid ?-synuclein oligomers in healthy asymptomatic LRRK2 mutation carriers  

PubMed Central

Mutations in the leucine-rich repeat kinase 2 gene are the most common cause of autosomal dominant Parkinson’s disease (PD). To assess the cerebrospinal fluid (CSF) levels of ?-synuclein oligomers in symptomatic and asymptomatic leucine-rich repeat kinase 2 mutation carriers, we used enzyme-linked immunosorbent assays (ELISA) to investigate total and oligomeric forms of ?-synuclein in CSF samples. The CSF samples were collected from 33 Norwegian individuals with leucine-rich repeat kinase 2 mutations: 13 patients were clinically diagnosed with PD and 20 patients were healthy, asymptomatic leucine-rich repeat kinase 2 mutation carriers. We also included 35 patients with sporadic PD (sPD) and 42 age-matched healthy controls. Levels of CSF ?-synuclein oligomers were significantly elevated in healthy asymptomatic individuals carrying leucine-rich repeat kinase 2 mutations (n = 20; P < 0.0079) and in sPD group (n = 35; P < 0.003) relative to healthy controls. Increased ?-synuclein oligomers in asymptomatic leucine-rich repeat kinase 2 mutation carriers showed a sensitivity of 63.0% and a specificity of 74.0%, with an area under the curve of 0.66, and a sensitivity of 65.0% and a specificity of 83.0%, with an area under the curve of 0.74 for sPD cases. An inverse correlation between CSF levels of ?- synuclein oligomers and disease severity and duration was observed. Our study suggests that quantification of ?-synuclein oligomers in CSF has potential value as a tool for PD diagnosis and presymptomatic screening of high-risk individuals. PMID:25309429

Aasly, Jan O.; Johansen, Krisztina K.; Brønstad, Gunnar; Warø, Bjørg J.; Majbour, Nour K.; Varghese, Shiji; Alzahmi, Fatimah; Paleologou, Katerina E.; Amer, Dena A. M.; Al-Hayani, Abdulmonem; El-Agnaf, Omar M. A.

2014-01-01

277

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

PubMed Central

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

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

278

miRNA expression profiles in cerebrospinal fluid and blood of patients with acute ischemic stroke.  

PubMed

The aims of the study were (1) to determine whether miRNAs (microRNAs) can be detected in the cerebrospinal fluid (CSF) and blood of patients with ischemic stroke and (2) to compare these miRNA profiles with corresponding profiles from other neurological patients to address whether the miRNA profiles of CSF or blood have potential usefulness as diagnostic biomarkers of ischemic stroke. CSF from patients with acute ischemic stroke (n?=?10) and patients with other neurological diseases (n?=?10) was collected by lumbar puncture. Blood samples were taken immediately after. Expression profiles in the cell-free fractions of CSF and blood were analyzed by a microarray technique (miRCURY LNA™ microRNA Array, Exiqon A/S, Denmark) using a quantitative PCR (qPCR) platform containing 378 miRNA primers. In total, 183 different miRNAs were detected in the CSF, of which two miRNAs (let-7c and miR-221-3p) were found upregulated in relation to stroke. In the blood, 287 different miRNAs were detected of which two miRNAs (miR-151a-3p and miR-140-5p) were found upregulated and one miRNA (miR-18b-5p) was found downregulated in the stroke group. Some miRNAs occurred exclusively in the CSF including miR-523-3p which was detected in 50 % of the stroke patients, whereas it was completely absent in controls. Our preliminary results demonstrate that it is possible to detect and profile miRNAs in CSF and blood from patients with neurological diseases. Some miRNAs appear differentially expressed in the CSF and others in the blood of stroke patients. Currently, we are validating our results in larger groups of patients. PMID:25127724

Sørensen, Sofie Sølvsten; Nygaard, Ann-Britt; Nielsen, Ming-Yuan; Jensen, Kai; Christensen, Thomas

2014-12-01

279

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

PubMed Central

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

2013-01-01

280

Pharmacokinetics of Colistin in Cerebrospinal Fluid after Intraventricular Administration of Colistin Methanesulfonate  

PubMed Central

Intraventricular colistin, administered as colistin methanesulfonate (CMS), is the last resource for the treatment of central nervous system infections caused by panresistant Gram-negative bacteria. The doses and daily regimens vary considerably and are empirically chosen; the cerebrospinal fluid (CSF) pharmacokinetics of colistin after intraventricular administration of CMS has never been characterized. Nine patients (aged 18 to 73 years) were treated with intraventricular CMS (daily doses of 2.61 to 10.44 mg). Colistin concentrations were measured using a selective high-performance liquid chromatography (HPLC) assay. The population pharmacokinetics analysis was performed with the P-Pharm program. The pharmacokinetics of colistin could be best described by the one-compartment model. The estimated values (means ± standard deviations) of apparent CSF total clearance (CL/Fm, where Fm is the unknown fraction of CMS converted to colistin) and terminal half-life (t1/2?) were 0.033 ± 0.014 liter/h and 7.8 ± 3.2 h, respectively, and the average time to the peak concentration was 3.7 ± 0.9 h. A positive correlation between CL/Fm and the amount of CSF drained (range 40 to 300 ml) was observed. When CMS was administered at doses of ?5.22 mg/day, measured CSF concentrations of colistin were continuously above the MIC of 2 ?g/ml, and measured values of trough concentration (Ctrough) ranged between 2.0 and 9.7 ?g/ml. Microbiological cure was observed in 8/9 patients. Intraventricular administration of CMS at doses of ?5.22 mg per day was appropriate in our patients, but since external CSF efflux is variable and can influence the clearance of colistin and its concentrations in CSF, the daily dose of 10 mg suggested by the Infectious Diseases Society of America may be more prudent. PMID:22687507

Cusato, Maria; Accetta, Giovanni; Marinò, Valeria; Procaccio, Francesco; Del Gaudio, Alfredo; Iotti, Giorgio A.; Regazzi, Mario

2012-01-01

281

Increases in Spinal Cerebrospinal Fluid Potassium Concentration Do Not Increase Isoflurane Minimum Alveolar Concentration in Rats  

PubMed Central

BACKGROUND Previous studies demonstrated that MAC for isoflurane directly correlates with the concentration of Na+ in cerebrospinal fluid surrounding the spinal cord, the primary site for mediation of the immobility produced by inhaled anesthetics. If this correlation resulted from increased irritability of the cord, then infusion of increased concentrations of potassium (K+) might be predicted to act similarly. However, an absence of effect of K+ might be interpreted to indicate that K+ channels do not mediate the immobility produced by inhaled anesthetics whereas Na+ channels remain as potential mediators. Accordingly, in the present study, we examined the effect of altering intrathecal concentrations of K+ on MAC. METHODS In rats prepared with chronic indwelling intrathecal catheters, we infused solutions deficient in K+ and with an excess of K+ into the lumbar space and measured MAC for isoflurane 24 h before, during, and 24 h after infusion. Rats similarly prepared were tested for the effect of altered osmolarity on MAC (accomplished by infusion of mannitol) and for the penetration of Na+ into the cord. RESULTS MAC of isoflurane never significantly increased with increasing concentrations of K+ infused intrathecally. At infused concentrations exceeding 12 times the normal concentration of KCl, i.e., 29 mEq/L, rats moved spontaneously at isoflurane concentrations just below, and sometimes at MAC, but the average MAC in these rats did not exceed their control MAC. At the largest infused concentration (58.1 mEq/L), MAC significantly decreased and did not subsequently return to normal (i.e., such large concentrations produced injury). Infusions of lower concentrations of K+ had no effect on MAC. Infusion of osmotically equivalent solutions of mannitol did not affect MAC. Na+ infused intrathecally measurably penetrated the spinal cord. CONCLUSIONS The results do not support a mediation or modulation of MAC by K+ channels. PMID:18713900

Shnayderman, Dimitry; Laster, Michael J.; Eger, Edmond I; Oh, Irene; Zhang, Yi; Jinks, Steven L.; Antognini, Joseph F.; Raines, Douglas E.

2009-01-01

282

PCR for Detection of Herpes Simplex Virus in Cerebrospinal Fluid: Alternative Acceptance Criteria for Diagnostic Workup  

PubMed Central

The determination of herpes simplex virus (HSV) infection using a PCR assay is one of the most commonly requested tests for analysis of cerebrospinal fluid (CSF), although only a very low proportion of results are positive. A previously reported study showed that selecting only those CSF samples with >5 leukocytes/mm3 or a protein level of >50 mg/dl was adequate for the diagnostic workup. The aim of the present study was to assess the reliability of alternative acceptance criteria based on elevated CSF white blood cell counts (>10 cells/mm3). We analyzed all requests for HSV PCR received between January 2008 and December 2011. CSF samples were accepted for analysis if they had >10 cells/mm3 or if the sample was from an immunocompromised patient or a child aged <2 years. In order to evaluate our selection criteria, we identified those CSF samples with a leukocyte count of 5 to 10 cells/mm3 or protein levels of >50 mg/dl in order to test them for HSV type 1 and 2 (HSV-1 and HSV-2) DNA. During the study period, 466 CSF samples were submitted to the microbiology laboratory for HSV PCR. Of these, 268 (57.5%) were rejected, and 198 (42.5%) were tested according to our routine criteria. Of the tested samples, 11 (5.5%) were positive for HSV DNA (7 for HSV-1 and 4 for HSV-2). Of the 268 rejected specimens, 74 met the criteria of >5 cells/mm3 and/or protein levels of >50 mg/dl. Of these, 70 (94.6%) were available for analysis. None of the samples yielded a positive HSV PCR result. Acceptance criteria based on CSF leukocyte counts, host immune status, and age can help to streamline the application of HSV PCR without reducing sensitivity. PMID:23804382

Alonso, Roberto; de Egea, Viviana; Usubillaga, Rafael; Muñoz, Patricia; Bouza, Emilio

2013-01-01

283

Characteristic abnormalities in cerebrospinal fluid biochemistry in children with cerebral malaria compared to viral encephalitis  

PubMed Central

Background In developing countries where Plasmodium falciparum malaria is endemic, viral encephalitis and cerebral malaria are found in the same population, and parasitemia with Plasmodium falciparum is common in asymptomatic children. The objective of this study was to investigate the cerebrospinal fluid (CSF) biochemistry in children with cerebral malaria compared to those with presumed viral encephalitis. Methods We studied the following CSF parameters: cell count, glucose, protein, lactic dehydrogenase (LDH) and adenosine deaminase (ADA) levels, in children with cerebral malaria, with presumed viral encephalitis, and in control subjects who had a lumbar puncture after a febrile convulsion with postictal coma. Results We recruited 12 children with cerebral malaria, 14 children with presumed viral encephalitis and 20 controls prospectively, over 2 years in the Government General Hospital in Kakinada, India. Patients with cerebral malaria had significantly lower CSF glucose, and higher protein, LDH, CSF/blood LDH ratio and CSF ADA levels but a lower CSF/serum ADA ratio compared to controls (p < 0.01). Patients with cerebral malaria had lower CSF white cell count, glucose, protein, LDH levels and CSF/serum ADA ratio compared to patients with presumed viral encephalitis. CSF/serum ADA ratio was lower in patients with cerebral malaria due to the fact that serum ADA levels were significantly higher in patients with cerebral malaria compared to the other two groups. A CSF/serum ADA ratio of <0.38 and a CSF glucose level of <3.4 mmol/l were selected as the cut-off values with the highest sensitivities and specificities for comparing the two conditions. Conclusion CSF/serum ADA ratio and CSF glucose levels were the best discriminators of cerebral malaria from presumed viral encephalitis in our study. Further studies are needed to explore their usefulness in epidemiological studies. PMID:16764711

Jakka, SR; Veena, S; Atmakuri, RM; Eisenhut, M

2006-01-01

284

Cerebrospinal fluid detection of interleukin-1? in phase of remission predicts disease progression in multiple sclerosis  

PubMed Central

Background Absence of clinical and radiological activity in relapsing–remitting multiple sclerosis (RRMS) is perceived as disease remission. We explored the role of persisting inflammation during remission in disease evolution. Methods Cerebrospinal fluid (CSF) levels of interleukin 1? (IL-1?), a major proinflammatory cytokine, were measured in 170 RRMS patients at the time of clinical and radiological remission. These patients were then followed up for at least 4 years, and clinical, magnetic resonance imaging (MRI) and optical coherence tomography (OCT) measures of disease progression were recorded. Results Median follow-up of RRMS patients was 5 years. Detection of CSF IL-1? levels at the time of remission did not predict earlier relapse or new MRI lesion formation. Detection of IL-1? in the CSF was instead associated with higher progression index (PI) and Multiple Sclerosis Severity Scale (MSSS) scores at follow-up, and the number of patients with sustained Expanded Disability Status Scale (EDSS) or Multiple Sclerosis Functional Composite worsening at follow-up was higher in individuals with detectable levels of IL-1?. Patients with undetectable IL-1? in the CSF had significantly lower PI and MSSS scores and a higher probability of having a benign MS phenotype. Furthermore, patients with undetectable CSF levels of IL-1? had less retinal nerve fiber layer thickness and macular volume alterations visualized by OCT compared to patients with detectable IL-1?. Conclusions Our results suggest that persistence of a proinflammatory environment in RRMS patients during clinical and radiological remission influences midterm disease progression. Detection of IL-1? in the CSF at the time of remission appears to be a potential negative prognostic factor in RRMS patients. PMID:24548694

2014-01-01

285

YKL-40 Is Elevated in Cerebrospinal Fluid from Patients with Purulent Meningitis  

PubMed Central

YKL-40, a member of the family 18 glycosyl hydrolases, is secreted by activated neutrophils and macrophages. It is a growth factor for connective tissue cells and a potent migration factor for endothelial cells and may function in inflammation and tissue remodeling. YKL-40 was determined in 134 cerebrospinal fluid (CSF) samples taken on admission from patients suspected of having meningitis (48 with purulent meningitis, 49 with lymphocytic meningitis, 5 with encephalitis, and 32 without evidence of meningitis). YKL-40 levels in CSF were significantly higher in patients with purulent meningitis (median, 663 ?g/liter [range, 20 to 8,960]) and encephalitis (5,430 ?g/liter [620 to 11,600]) than in patients with lymphocytic meningitis (137 ?g/liter [41 to 1,865]) or patients without meningitis (167 ?g/liter [24 to 630]) (Kruskal-Wallis and Dunn multiple comparison tests, P < 0.001). CSF YKL-40 levels were also determined for 26 patients with purulent meningitis having a repuncture, and patients who died (n = 5) had significantly higher YKL-40 levels than patients who survived (n = 21) (2,100 ?g/liter [1,160 to 7,050] versus 885 ?g/liter [192 to 15,400], respectively; Mann-Whitney test, P = 0.018). YKL-40 was most likely locally produced, since patients with infections of the central nervous system had CSF YKL-40 levels that were at least 10-fold higher than the corresponding levels in serum (2,033 ?g/liter [470 to 11,600] versus 80 ?g/liter [19 to 195]). The CSF neopterin level was the biochemical parameter in CSF and blood that correlated best with CSF YKL-40 levels, indicating that YKL-40 may be produced by activated macrophages within the central nervous system. In conclusion, high levels of YKL-40 in CSF are found in patients with purulent meningitis. PMID:11986266

Østergaard, Christian; Johansen, Julia S.; Benfield, Thomas; Price, Paul A.; Lundgren, Jens D.

2002-01-01

286

Methodological Aspects of ELISA Analysis of Thioredoxin 1 in Human Plasma and Cerebrospinal Fluid  

PubMed Central

Thioredoxin-1 (Trx1) is a protein antioxidant involved in major cellular processes. Increased plasma levels of Trx1 have been associated with human diseases suggesting that Trx1 is a marker for oxidative stress with putative clinical use. However, the reported mean levels of Trx1 in the control cohorts vary a hundred-fold between studies (0.8–87 ng/ml), possibly due to methodological differences between the capture ELISA used in the different studies. The aim of this study was to investigate methodological aspects related to the ELISA measurement of Trx1. ELISAs utilizing different capture and detection combinations of antibodies to Trx1 and as well as recombinant human (rh) Trx1 standards from two sources were characterized. The different ELISAs were subsequently used to measure Trx1 in human plasma and cerebrospinal fluid samples (CSF) from healthy donors and from patients with various neurological diagnoses. The Trx1 standards differed in their content of monomeric and oligomeric Trx1, which affected the ELISAs composed of different antibody combinations. Thus, the levels of Trx1 determined in human plasma and CSF samples varied depending on the antibody used in the ELISAs and on the rhTrx1 standard. Furthermore, the relevance of preventing interference by heterophilic antibodies (HA) in human plasma and CSF was investigated. The addition of a HA blocking buffer to human samples drastically reduced the ELISA signals in many samples showing that HA are likely to cause false positive results unless they are blocked. In conclusion, the study shows that the design of a Trx1 ELISA in regards to antibodies and standards used has an impact on the measured Trx1 levels. Importantly, analyses of human plasma and CSF without preventing HA interference may obscure the obtained data. Overall, the results of this study are crucial for the improvement of future studies on the association of Trx1 levels with various diseases. PMID:25075746

Lundberg, Mathias; Curbo, Sophie; Reiser, Kathrin; Masterman, Thomas; Braesch-Andersen, Sten; Areström, Irene; Ahlborg, Niklas

2014-01-01

287

Inflammasome Proteins in Cerebrospinal Fluid of Brain Injured Patients are Biomarkers of Functional Outcome  

PubMed Central

Object Traumatic brain injury (TBI), the third most common central nervous system (CNS) pathology, plagues 5.3 million Americans with permanent TBI-related disabilities. To evaluate injury severity and prognosis, physicians rely on clinical variables. Here we seek objective, biochemical markers reflecting molecular injury mechanisms specific to the CNS as more accurate measurements of injury severity and outcome. One such secondary injury mechanism, the innate immune response, is regulated by the inflammasome, a molecular platform that activates caspase-1 and interleukin-1?. Methods We investigated whether inflammasome components are present in the cerebrospinal fluid (CSF) of 23 TBI patients, and whether levels of inflammasome components correlate with outcome. We performed immunoblot analysis of CSF samples from TBI patients and non-trauma controls and assessed outcome five months post-injury by the Glasgow Outcome Scale (GOS). Data were analyzed by Mann-Whitney U tests and linear regression analysis. Results Patients with severe or moderate cranial trauma exhibited significantly higher CSF levels of the inflammasome proteins apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, and NAcht leucine-rich-repeat protein-1 (NALP-1) compared to non-trauma controls (P < 0.0001; P = 0.0029; P = 0.0202, respectively). Expression of each protein correlated significantly with GOS at five months post-injury (P < 0.05). ASC, caspase-1, and NALP-1 were significantly higher in the CSF of patients with unfavorable outcomes, including death and severe disability (P < 0.0001). Conclusions NALP-1 inflammasome proteins are potential biomarkers to assess TBI severity, outcome, and the secondary injury mechanisms impeding recovery, serving as adjuncts to clinical predictors. PMID:23061392

Adamczak, Stephanie; Dale, Gordon; de Rivero Vaccari, Juan Pablo; Bullock, M. Ross; Dietrich, W. Dalton; Keane, Robert W.

2013-01-01

288

Overton's Rule Helps To Estimate the Penetration of Anti-Infectives into Patients' Cerebrospinal Fluid  

PubMed Central

In 1900, Ernst Overton found that the entry of anilin dyes through the cell membranes of living cells depended on the lipophilicity of the dyes. The brain is surrounded by barriers consisting of lipid layers that possess several inward and outward active transport systems. In the absence of meningeal inflammation, the cerebrospinal fluid (CSF) penetration of anti-infectives in humans estimated by the ratio of the area under the concentration-time curve (AUC) in CSF (AUCCSF) to that in serum (AUCCSF/AUCS) correlated positively with the lipid-water partition coefficient at pH 7.0 (log D) (Spearman's rank correlation coefficient rS = 0.40; P = 0.01) and negatively with the molecular mass (MM) (rS = ?0.33; P = 0.04). The ratio of AUCCSF to the AUC of the fraction in serum that was not bound (AUCCSF/AUCS,free) strongly correlated with log D (rS = 0.67; P < 0.0001). In the presence of meningeal inflammation, AUCCSF/AUCS also correlated positively with log D (rS = 0.46; P = 0.002) and negatively with the MM (rS = ?0.37; P = 0.01). The correlation of AUCCSF/AUCS,free with log D (rS = 0.66; P < 0.0001) was as strong as in the absence of meningeal inflammation. Despite these clear correlations, Overton's rule was able to explain only part of the differences in CSF penetration of the individual compounds. The site of CSF withdrawal (lumbar versus ventricular CSF), age of the patients, underlying diseases, active transport, and alterations in the pharmacokinetics by comedications also appeared to strongly influence the CSF penetration of the drugs studied. PMID:22106225

Djukic, Marija; Munz, Martin; Sörgel, Fritz; Holzgrabe, Ulrike; Eiffert, Helmut

2012-01-01

289

Routine Testing for Anaerobic Bacteria in Cerebrospinal Fluid Cultures Improves Recovery of Clinically Significant Pathogens  

PubMed Central

In North America, the widespread use of vaccines targeting Haemophilus influenzae type b and Streptococcus pneumoniae have dramatically altered the epidemiology of bacterial meningitis, while the methodology for culturing cerebrospinal fluid (CSF) specimens has remained largely unchanged. The aims of this study were 2-fold: to document the current epidemiology of bacterial meningitis at a tertiary care medical center and to assess the clinical utility of routinely querying for anaerobes in CSF cultures. To that end, we assessed CSF cultures submitted over a 2-year period. A brucella blood agar (BBA) plate, incubated anaerobically for 5 days, was included in the culture procedure for all CSF specimens during the second year of evaluation. In the pre- and postimplementation years, 2,353 and 2,302 CSF specimens were cultured, with 49 and 99 patients having positive culture results, respectively. The clinical and laboratory data for patients with positive cultures were reviewed. Anaerobic bacteria were isolated in the CSF samples from 33 patients post-BBA compared to two patients pre-BBA (P = 0.01). The anaerobic isolates included Bacteroides thetaiotaomicron (n = 1), Propionibacterium species (n = 15), and Propionibacterium acnes (n = 19) isolates; all of these isolates were recovered on the BBA. Eight of the 35 patients from whom anaerobic organisms were isolated received antimicrobial therapy. Although six of these patients had central nervous system hardware, two patients did not have a history of a neurosurgical procedure and had community-acquired anaerobic bacterial meningitis. This study demonstrates that the simple addition of an anaerobically incubated BBA to the culture of CSF specimens enhances the recovery of clinically significant anaerobic pathogens. PMID:24622102

Pittman, Meredith E.; Thomas, Benjamin S.; Wallace, Meghan A.; Weber, Carol J.

2014-01-01

290

Adult cerebrospinal fluid inhibits neurogenesis but facilitates gliogenesis from fetal rat neural stem cells.  

PubMed

Neural stem cells (NSCs) are a promising source for cell replacement therapies for neurological diseases. Administration of NSCs into the cerebrospinal fluid (CSF) offers a nontraumatic transplantation method into the brain. However, cell survival and intraparenchymal migration of the transplants are limited. Furthermore, CSF was recently reported to be an important milieu for controlling stem cell processes in the brain. We studied the effects of adult human leptomeningeal CSF on the behavior of fetal rat NSCs. CSF increased survival of NSCs compared with standard culture media during stem cell maintenance and differentiation. The presence of CSF enhanced NSC differentiation, leading to a faster loss of self-renewal capacity and faster and stronger neurite outgrowth. Some of these effects (mainly cell survival, neurite brancing) were blocked by addition of the bone morphogenic protein (BMP) inhibitor noggin. After differentiation in CSF, significantly fewer MAP2ab(+) neurons were found, but there were more GFAP(+) astroglia compared with standard media. By RT-PCR analysis, we determined a decrease of mRNA of the NSC marker gene Nestin but an increase of Gfap mRNA during differentiation up to 72 hr in CSF compared with standard media. Our data demonstrate that adult human leptomeningeal CSF enhances cell survival of fetal rat NSCs during proliferation and differentiation. Furthermore, CSF provides a stimulus for gliogenesis but inhibits neurogenesis from fetal NSCs. Our data suggest that CSF contains factors such as BMPs regulating NSC behavior, and we hypothesize that fast differentiation of NSCs in CSF leads to a rapid loss of migration capacity of intrathecally transplanted NSCs. PMID:19530161

Buddensiek, Judith; Dressel, Alexander; Kowalski, Michael; Storch, Alexander; Sabolek, Michael

2009-11-01

291

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

PubMed Central

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

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

2014-01-01

292

Cerebrospinal fluid markers including trefoil factor 3 are associated with neurodegeneration in amyloid-positive individuals.  

PubMed

We aimed to identify cerebrospinal fluid (CSF) biomarkers associated with neurodegeneration in individuals with and without CSF evidence of Alzheimer pathology. We investigated 287 Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects (age=74.9±6.9; 22/48/30% with Alzheimer's disease/mild cognitive impairment/controls) with CSF multiplex analyte data and serial volumetric MRI. We calculated brain and hippocampal atrophy rates, ventricular expansion and Mini Mental State Examination decline. We used false discovery rate corrected regression analyses to assess associations between CSF variables and atrophy rates in individuals with and without amyloid pathology, adjusting in stages for tau, baseline volume, p-tau, age, sex, ApoE4 status and diagnosis. Analytes showing statistically significant independent relationships were entered into reverse stepwise analyses. Adjusting for tau, baseline volume, p-tau, age, sex and ApoE4, 4/83 analytes were significantly independently associated with brain atrophy rate, 1/83 with ventricular expansion and 2/83 with hippocampal atrophy. The strongest CSF predictor for the three atrophy measures was low trefoil factor 3 (TFF3). High cystatin C (CysC) was associated with higher whole brain atrophy and hippocampal atrophy rates. Lower levels of vascular endothelial growth factor and chromogranin A (CrA) were associated with higher whole brain atrophy. In exploratory reverse stepwise analyses, lower TFF3 was associated with higher rates of whole brain, hippocampal atrophy and ventricular expansion. Lower levels of CrA were associated with higher whole brain atrophy rate. The relationship between low TFF3 and increased hippocampal atrophy rate remained after adjustment for diagnosis. We identified a series of CSF markers that are independently associated with rate of neurodegeneration in amyloid-positive individuals. TFF3, a substrate for NOTCH processing may be an important biomarker of neurodegeneration across the Alzheimer spectrum. PMID:25072324

Paterson, R W; Bartlett, J W; Blennow, K; Fox, N C; Shaw, L M; Trojanowski, J Q; Zetterberg, H; Schott, J M

2014-01-01

293

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

PubMed Central

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

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

2013-01-01

294

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

PubMed

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

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

2013-01-01

295

Intracranial pressure pulse waveform correlates with aqueductal cerebrospinal fluid stroke volume  

PubMed Central

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

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

2012-01-01

296

Identification of microRNAs in the cerebrospinal fluid as biomarker for the diagnosis of glioma  

PubMed Central

Malignant gliomas are the most common and lethal primary intracranial tumors. To date, no reliable biomarkers for the detection and risk stratification of gliomas have been identified. Recently, we demonstrated significant levels of microRNAs (miRNAs) to be present in cerebrospinal fluid (CSF) samples from patients with primary CNS lymphoma. Because of the involvement of miRNA in carcinogenesis, miRNAs in CSF may serve as unique biomarkers for minimally invasive diagnosis of glioma. The objective of this pilot study was to identify differentially expressed microRNAs in CSF samples from patients with glioma as potential novel glioma biomarkers. With use of a candidate approach of miRNA quantification by reverse-transcriptase polymerase chain reaction (qRT-PCR), miRNAs with significant levels in CSF samples from patients with gliomas were identified. MiR-15b and miR-21 were differentially expressed in CSF samples from patients with gliomas, compared to control subjects with various neurologic disorders, including patients with primary CNS lymphoma and carcinomatous brain metastases. Receiver-operating characteristic analysis of miR-15b level revealed an area under the curve of 0.96 in discriminating patients with glioma from patients without glioma. Moreover, inclusion of miR-15b and miR-21 in combined expression analyses resulted in an increased diagnostic accuracy with 90% sensitivity and 100% specificity to distinguish patients with glioma from control subjects and patients with primary CNS lymphoma. In conclusion, the results of this pilot study demonstrate that miR-15b and miR-21 are markers for gliomas, which can be assessed in the CSF by means of qRT-PCR. Accordingly, miRNAs in the CSF have the potential to serve as novel biomarkers for the detection of gliomas. PMID:21937590

Baraniskin, Alexander; Kuhnhenn, Jan; Schlegel, Uwe; Maghnouj, Abdelouahid; Zöllner, Hannah; Schmiegel, Wolf; Hahn, Stephan; Schroers, Roland

2012-01-01

297

Proteomic Changes in Cerebrospinal Fluid of Presymptomatic and Affected Persons Carrying Familial Alzheimer Disease Mutations  

PubMed Central

Objective To identify cerebrospinal fluid (CSF) protein changes in persons who will develop familial Alzheimer disease (FAD) due to PSEN1 and APP mutations, using unbiased proteomics. Design We compared proteomic profiles of CSF from individuals with FAD who were mutation carriers (MCs) and related noncarriers (NCs). Abundant proteins were depleted and samples were analyzed using liquid chromatography– electrospray ionization–mass spectrometry on a high-resolution time-of-flight instrument. Tryptic peptides were identified by tandem mass spectrometry. Proteins differing in concentration between the MCs and NCs were identified. Setting A tertiary dementia referral center and a proteomic biomarker discovery laboratory. Participants Fourteen FAD MCs (mean age, 34.2 years; 10 are asymptomatic, 12 have presenilin-1 [PSEN1] gene mutations, and 2 have amyloid precursor protein [APP] gene mutations) and 5 related NCs (mean age, 37.6 years). Results Fifty-six proteins were identified, represented by multiple tryptic peptides showing significant differences between MCs and NCs (46 upregulated and 10 downregulated); 40 of these proteins differed when the analysis was restricted to asymptomatic individuals. Fourteen proteins have been reported in prior proteomic studies in late-onset AD, including amyloid precursor protein, transferrin, ?1?-glycoprotein, complement components, afamin precursor, spondin 1, plasminogen, hemopexin, and neuronal pentraxin receptor. Many other proteins were unique to our study, including calsyntenin 3, AMPA (?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) 4 glutamate receptor, CD99 antigen, di-N-acetyl-chitobiase, and secreted phosphoprotein 1. Conclusions We found much overlap in CSF protein changes between individuals with presymptomatic and symptomatic FAD and those with late-onset AD. Our results are consistent with inflammation and synaptic loss early in FAD and suggest new presymptomatic biomarkers of potential usefulness in drug development. PMID:22232349

Ringman, John M.; Schulman, Howard; Becker, Chris; Jones, Ted; Bai, Yuchen; Immermann, Fred; Cole, Gregory; Sokolow, Sophie; Gylys, Karen; Geschwind, Daniel H.; Cummings, Jeffrey L.; Wan, Hong I.

2013-01-01

298

Comparison of cerebrospinal fluid monoamine metabolite levels in dominant-aggressive and non-aggressive dogs.  

PubMed

Aggression has been shown to be related to reduced serotonergic activity in humans and non-human primates, and in rodents. We now studied the relationship between cerebrospinal fluid (CSF) monoamine metabolites and canine aggression in 21 dominant-aggressive dogs (Canis familiaris) and 19 controls. The diagnosis of dominance-related aggression was based upon a history of biting family members in contexts associated with dominance challenges. Post-mortem CSF 5-HIAA, MHPG and HVA were measured by high-performance liquid chromatography using electrochemical detection. Concentrations of CSF 5-HIAA (P = 0.01) and HVA (P < 0.001) were lower in the aggressive group (median values: 5-HIAA 202.0 pmol/ml; HVA 318.0 pmol/ml) than in controls (5-HIAA 298.0 pmol/ml; HVA 552.0 pmol/ml). No differences were noted in CSF MHPG levels. Differences in 5-HIAA were maintained after controlling for breed and age of dogs, but HVA differences may have been breed-dependent. Lower levels of 5-HIAA (P = 0.02) and HVA (P = 0.04) were found in the subgroup of aggressive dogs with a history of biting without warning (5-HIAA 196.0 pmol/ml; HVA 302.0 pmol/ml) compared to dogs that warned (5-HIAA 244.0 pmol/ml; HVA 400.0 pmol/ml). This study suggests that reduced serotonergic function is associated with aggressive behavior and impaired impulse control in dogs, a finding that is consistent with observations in primates, and suggests that serotonin modulates aggressive behavior throughout mammals. PMID:8861609

Reisner, I R; Mann, J J; Stanley, M; Huang, Y Y; Houpt, K A

1996-04-01

299

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

PubMed Central

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

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

300

Cerebrospinal fluid stimulates leptomeningeal and meningioma cell proliferation and activation of STAT3.  

PubMed

The role of cerebrospinal fluid (CSF) in the pathogenesis of meningiomas is unknown. Cell cultures from three human leptomeninges, five WHO grade I and seven grade II meningiomas were treated with remnant CSF from 22 patients with no central nervous system disease and normal cell indices. Cells were evaluated by CyQUANT for DNA synthesis/cell proliferation and by western blots for phosphorylation/activation of growth regulatory pathways activated in meningiomas including JAK1-STAT3, MEK1-p44/42MAPK, Akt-mTOR and Rb. Analysis of Caspase 3 activation and survivin was also performed. Finally, the effects of PDGF neutralizing antibody and cucurbitacin, a STAT3 inhibitor on CSF stimulation were tested. Compared to controls and the mitogen PDGF-BB, various CSF samples significantly stimulated DNA synthesis/cell proliferation in 20 and 22 week leptomeningeal cultures and all of the grade I and II meningioma cells tested. Collectively CSF samples, from multiple different patients, stimulated DNA synthesis in tests of 23 of 32 grade I and 18 of 28 grade II meningioma cells. CSF stimulated phosphorylation/activation of STAT3 and reduced p44/42 MAPK in the leptomeningeal, all three grade I and 1 of three grade II meningioma cells. CSF did not affect Caspase 3 activity or survivin levels. PDGF neutralizing antibody had no effect on CSF stimulation but cucurbitacin blocked PDGF and CSF stimulation. While there are limitations to the CSF available since they were not from "normal" volunteers, the studies suggest that, in some settings, CSF is potentially mitogenic to leptomeningeal and meningioma cells and may act, in part, via activation of STAT3. PMID:21971737

Johnson, Mahlon D; O'Connell, Mary; Facik, Michael; Maurer, Paul; Jahromi, Babak; Pilcher, Webster

2012-03-01

301

Cerebrospinal fluid mononuclear cell counts influence CSF HIV-1 RNA levels.  

PubMed

This study evaluated the relation between cerebrospinal fluid (CSF) mononuclear cells (MNC) and CSF HIV-1 RNA levels. HIV-1 RNA levels in plasma and CSF were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) in 58 consecutive patients with neurologic symptoms and late HIV-1 infection. The majority of the patients had no central nervous system (CNS) complication (n = 36), 11 had AIDS dementia complex (ADC) and 11 had CNS opportunistic infection (CNS OI). CSF cell counts were analyzed using a method that also evaluated hypocellular CSF (i.e., from 0.1 x 10(6) cells/L). A strong correlation was found between CSF MNC and CD4+ lymphocyte counts in blood (r = 0.58; p < .0001). HIV-1 RNA was detected in all plasma samples and in 38 of 58 (66%) of the cell-free CSF samples. CSF HIV-1 RNA was less frequently detected in patients with hypocellular CSF than in patients with normocellular or pleocytic CSF (13 of 28 patients [46%] versus 10 of 14 patients [71%] versus 15 of 16 patients [94%], respectively). The levels of CSF HIV-1 RNA correlated with the CSF MNC count (r = 0.61; p < .0001). The correlation also remained strong within the clinical subgroups of CNS asymptomatic patients (r = 0.55; p < .001) and ADC patients (r = 0.79; p < .001), but not among CNS OI patients (r = 0.19). Patients with CNS OI were found to have higher CSF HIV-1 RNA levels than the patients without evidence of CNS complication. Thus, a close relation was found between CSF HIV-1 RNA levels and CSF MNC counts. These data support the hypothesis that a substantial part of the virus in the CSF of HIV-1-infected patients is locally produced by CSF MNC. PMID:9495220

Martin, C; Albert, J; Hansson, P; Pehrsson, P; Link, H; Sönnerborg, A

1998-03-01

302

Preoperative cerebrospinal fluid cytokine levels and the risk of postoperative delirium in elderly hip fracture patients  

PubMed Central

Background Aging and neurodegenerative disease predispose to delirium and are both associated with increased activity of the innate immune system resulting in an imbalance between pro- and anti-inflammatory mediators in the brain. We examined whether hip fracture patients who develop postoperative delirium have altered levels of inflammatory mediators in cerebrospinal fluid (CSF) prior to surgery. Methods Patients were 75 years and older and admitted for surgical repair of an acute hip fracture. CSF samples were collected preoperatively. In an exploratory study, we measured 42 cytokines and chemokines by multiplex analysis. We compared CSF levels between patients with and without postoperative delirium and examined the association between CSF cytokine levels and delirium severity. Delirium was diagnosed with the Confusion Assessment Method; severity of delirium was measured with the Delirium Rating Scale Revised-98. Mann–Whitney U tests or Student t-tests were used for between-group comparisons and the Spearman correlation coefficient was used for correlation analyses. Results Sixty-one patients were included, of whom 23 patients (37.7%) developed postsurgical delirium. Concentrations of Fms-like tyrosine kinase-3 (P=0.021), Interleukin-1 receptor antagonist (P=0.032) and Interleukin-6 (P=0.005) were significantly lower in patients who developed delirium postoperatively. Conclusions Our findings fit the hypothesis that delirium after surgery results from a dysfunctional neuroinflammatory response: stressing the role of reduced levels of anti-inflammatory mediators in this process. Trial registration The Effect of Taurine on Morbidity and Mortality in the Elderly Hip Fracture Patient. Registration number: NCT00497978. Local ethical protocol number: NL16222.094.07. PMID:24093540

2013-01-01

303

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

PubMed

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

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

304

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

PubMed Central

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 appreciation of CSF pressure (CSFP) is being generated by fresh insights on peptidergic regulatory servomechanisms, the role of dysfunctional ependyma and circumventricular organs in causing congenital hydrocephalus, and the clinical use of algorithms to delineate CSFP waveforms for diagnostic and prognostic utility. Increasing attention focuses on CSF flow: how it impacts cerebral metabolism and hemodynamics, neural stem cell progression in the subventricular zone, and catabolite/peptide clearance from the CNS. The pathophysiological significance of changes in CSF volume is assessed from the respective viewpoints of hemodynamics (choroid plexus blood flow and pulsatility), hydrodynamics (choroidal hypo- and hypersecretion) and neuroendocrine factors (i.e., coordinated regulation by atrial natriuretic peptide, arginine vasopressin and basic fibroblast growth factor). In aging, normal pressure hydrocephalus and Alzheimer's disease, the expanding CSF space reduces the CSF turnover rate, thus compromising the CSF sink action to clear harmful metabolites (e.g., amyloid) from the CNS. Dwindling CSF dynamics greatly harms the interstitial environment of neurons. Accordingly the altered CSF composition in neurodegenerative diseases and senescence, because of adverse effects on neural processes and cognition, needs more effective clinical management. CSF recycling between subarachnoid space, brain and ventricles promotes interstitial fluid (ISF) convection with both trophic and excretory benefits. Finally, CSF reabsorption via multiple pathways (olfactory and spinal arachnoidal bulk flow) is likely complemented by fluid clearance across capillary walls (aquaporin 4) and arachnoid villi when CSFP and fluid retention are markedly elevated. A model is presented that links CSF and ISF homeostasis to coordinated fluxes of water and solutes at both the blood-CSF and blood-brain transport interfaces. Outline 1 Overview 2 CSF formation 2.1 Transcription factors 2.2 Ion transporters 2.3 Enzymes that modulate transport 2.4 Aquaporins or water channels 2.5 Receptors for neuropeptides 3 CSF pressure 3.1 Servomechanism regulatory hypothesis 3.2 Ontogeny of CSF pressure generation 3.3 Congenital hydrocephalus and periventricular regions 3.4 Brain response to elevated CSF pressure 3.5 Advances in measuring CSF waveforms 4 CSF flow 4.1 CSF flow and brain metabolism 4.2 Flow effects on fetal germinal matrix 4.3 Decreasing CSF flow in aging CNS 4.4 Refinement of non-invasive flow measurements 5 CSF volume 5.1 Hemodynamic factors 5.2 Hydrodynamic factors 5.3 Neuroendocrine factors 6 CSF turnover rate 6.1 Adverse effect of ventriculomegaly 6.2 Attenuated CSF sink action 7 CSF composition 7.1 Kidney-like action of CP-CSF system 7.2 Altered CSF biochemistry in aging and disease 7.3 Importance of clearance transport 7.4 Therapeutic manipulation of composition 8 CSF recycling in relation to ISF dynamics 8.1 CSF exchange with brain interstitium 8.2 Components of ISF movement in brain 8.3 Compromised ISF/CSF dynamics and amyloid retention 9 CSF reabsorption 9.1 Arachnoidal outflow resistance 9.2 Arachnoid villi vs. olfactory drainage routes 9.3 Fluid reabsorption along spinal nerves 9.4 Reabsorption across capillary aquaporin channels 10 Developing translationally effective models for restoring CSF balance 11 Conclusion PMID:18479516

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

2008-01-01

305

Effect of Head Position on Cerebrospinal Fluid Pressure in Cats: Comparison with Artificial Model  

PubMed Central

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

Klarica, Marijan; Radoš, Milan; Dragani?, Pero; Erceg, Gorislav; Oreškovi?, Darko; Marakovi?, Jurica; Bulat, Marin

2006-01-01

306

Neoplastic autovagotomy causing gastric stasis.  

PubMed Central

Neoplastic autovagotomy causing atonic gastric stasis is extremely rare. Two cases are reported in which marked gastric stasis was complicated by a bezoar and a gastric volvulus respectively. Both cases were associated with a left hilar bronchial carcinoma, and malignant invasion of the vagus nerve may have been the underlying cause. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:482188

Thomas, W. E.; Fletcher, M. S.

1979-01-01

307

Mass spectrometric analysis of cerebrospinal fluid protein for glioma and its clinical application  

PubMed Central

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

Yu, Jiekai; Shen, Hong; Zhang, Jianmin; Liu, Weiguo; Chen, Zhe; He, Shuda; Zheng, Shu

2014-01-01

308

Utility of Measuring (1,3)-?-d-Glucan in Cerebrospinal Fluid for Diagnosis of Fungal Central Nervous System Infection.  

PubMed

(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

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; Zhang, Sean X

2015-01-01

309

Raman spectroscopy provides a powerful, rapid diagnostic tool for the detection of tuberculous meningitis in ex vivo cerebrospinal fluid samples  

PubMed Central

In this letter, we propose a novel method for diagnosis of tuberculous meningitis using Raman spectroscopy. The silicate Raman signature obtained from Mycobacterium tuberculosis positive cases enables specific and sensitive detection of tuberculous meningitis from acquired cerebrospinal fluid samples. The association of silicates with the tuberculosis mycobacterium is discussed. We envision that this new method will facilitate rapid diagnosis of tuberculous meningitis without application of exogenous reagents or dyes and can be aptly used as a complementary screening tool to the existing gold standard methods. Typical Raman spectra of the CSF sample clinically diagnosed as tuberculosis meningitis. PMID:22887773

Sathyavathi, R.; Dingari, Narahara Chari; Barman, Ishan; Prasad, P. S. R.; Prabhakar, Subhashini; Rao, D. Narayana; Dasari, Ramachandra R.; Undamatla, Jayanthi

2014-01-01

310

Simian cytomegalovirus-related stealth virus isolated from the cerebrospinal fluid of a patient with bipolar psychosis and acute encephalopathy.  

PubMed

A cytopathic 'stealth' virus was cultured from the cerebrospinal fluid of a patient with a bipolar psychotic disorder who developed a severe encephalopathy leading to a vegetative state. DNA sequencing of a polymerase chain reaction-amplified product from infected cultures has identified the virus as an African green monkey simian cytomegalovirus (SCMV)-related stealth virus. The virus is similar to the SCMV-related stealth virus isolated from a patient with chronic fatigue syndrome. The findings support the concepts that stealth viruses can account for a spectrum of dysfunctional brain diseases and that some of these viruses may have arisen from live polio viral vaccines. PMID:8888270

Martin, W J

1996-01-01

311

Analysis of L-serine-O-phosphate in cerebrospinal spinal fluid by derivatization-liquid chromatography/mass spectrometry.  

PubMed

L-serine-O-phosphate (L-SOP), the precursor of L-serine, is a potent agonist against the group III metabotropic glutamate receptors (mGluRs) and, thus, is of interest as a potential biomarker for monitoring modulation of neurotransmitter release. So far, no reports are available on the analysis of L-SOP in cerebrospinal fluid (CSF). Here a novel method is presented to determine L-SOP levels in CSF employing precolumn derivatization with (5-N-succinimidoxy-5-oxopentyl)triphenylphosphonium bromide (SPTPP) coupled to liquid chromatography/mass spectrometry (derivatization-LC/MS, d-LC/MS). PMID:24534252

McNaney, Colleen A; Benitex, Yulia; Luchetti, David; Labasi, Jeffrey M; Olah, Timothy V; Morgan, Daniel G; Drexler, Dieter M

2014-05-01

312

Clincal, Cerebrospinal Fluid and Pathological Findings and Outcomes in HIV-Positive and HIV-Negative Patients with Tuberculous Meningitis  

Microsoft Academic Search

Background: The early diagnosis of tuberculous (TB) meningitis remains difficult. In South Africa, the HIV epidemic has shifted the spectrum\\u000a of meningitis towards chronic infections (mainly tuberculosis [TB] and cryptococcosis). This study aimed to analyse clinical,\\u000a cerebrospinal fluid (CSF) and pathological findings and outcomes in TB meningitis to evaluate whether HIV infection significantly\\u000a influences the characteristic findings.\\u000a \\u000a \\u000a \\u000a \\u000a Patients and Methods:

C.-M. Schutte

2001-01-01

313

microRNA (miRNA) speciation in Alzheimer’s disease (AD) cerebrospinal fluid (CSF) and extracellular fluid (ECF)  

PubMed Central

Human cerebrospinal fluid (CSF), produced by the choroid plexus and secreted into the brain ventricles and subarachnoid space, plays critical roles in intra-cerebral transport and the biophysical and immune protection of the brain. CSF composition provides valuable insight into soluble pathogenic bio-markers that may be diagnostic for brain disease. In these experiments we analyzed amyloid beta (A?) peptide and micro RNA (miRNA) abundance in CSF and in short post-mortem interval (PMI <2.1 hr) brain tissue-derived extracellular fluid (ECF) from Alzheimer’s disease (AD) and age-matched control neocortex. There was a trend for decreased abundance of A?42 in the CSF and ECF in AD but it did not reach statistical significance (mean age ~72 yr; N=12; p~0.06, ANOVA). The most abundant nucleic acids in AD CSF and ECF were miRNAs, and their speciation and inducibility were studied further. Fluorescent miRNA-array-based analysis indicated significant increases in miRNA-9, miRNA-125b, miRNA-146a, miRNA-155 in AD CSF and ECF (N=12; p<0.01, ANOVA). Primary human neuronal-glial (HNG) cell co-cultures stressed with AD-derived ECF also displayed an up-regulation of these miRNAs, an effect that was quenched using the anti-NF-?B agents caffeic acid phenethyl ester (CAPE) or 1-fluoro-2-[2-(4-methoxy-phenyl)-ethenyl]-benzene (CAY10512). Increases in miRNAs were confirmed independently using a highly sensitive LED-Northern dot-blot assay. Several of these NF-?B-sensitive miRNAs are known to be up-regulated in AD brain, and associate with the progressive spreading of inflammatory neurodegeneration. The results indicate that miRNA-9, miRNA-125b, miRNA-146a and miRNA-155 are CSF- and ECF-abundant, NF-?B-sensitive pro-inflammatory miRNAs, and their enrichment in circulating CSF and ECF suggest that they may be involved in the modulation or proliferation of miRNA-triggered pathogenic signaling throughout the brain and central nervous system (CNS). PMID:23301201

Alexandrov, Peter N; Dua, Prerna; Hill, James M; Bhattacharjee, Surjyadipta; Zhao, Yuhai; Lukiw, Walter J

2012-01-01

314

Use of polymerase chain reaction and rabbit infectivity testing to detect Treponema pallidum in amniotic fluid, fetal and neonatal sera, and cerebrospinal fluid.  

PubMed Central

The diagnosis of congenital syphilis continues to pose a difficult clinical challenge. Because the serodiagnosis of congenital syphilis has significant limitations, the direct detection of Treponema pallidum in suspect neonatal tissues or body fluids represents a desirable alternate diagnostic strategy. We developed and applied the polymerase chain reaction (PCR) for the detection of T. pallidum in clinical material relevant to the diagnosis of congenital syphilis but which typically contain factors inhibitory for the PCR. Four methods of specimen processing were examined to circumvent PCR inhibition; clinical materials included amniotic fluids, neonatal sera, and neonatal cerebrospinal fluids. The PCR was 100% specific for T. T. pallidum compared with the sensitive rabbit infectivity test (RIT) for all clinical materials tested. For amniotic fluids, the PCR was 100% sensitive when correlated with the RIT but had a lesser sensitivity when applied to sera or cerebrospinal fluids, which typically contain few treponemes. The combined sensitivity of the PCR for all clinical samples was 78%. Positive PCR results also were obtained among some clinical specimens for which RIT was not performed; these results correlated well with either stigmata or risk factors for congenital syphilis. The combined results suggest that the PCR can be a useful adjunct to the diagnosis and clinical management of congenital syphilis and that it will provide a valuable tool for investigations of the pathogenesis of the disorder. Images PMID:1761693

Grimprel, E; Sanchez, P J; Wendel, G D; Burstain, J M; McCracken, G H; Radolf, J D; Norgard, M V

1991-01-01

315

Time-Resolved Fluorometry PCR Assay for Rapid Detection of Herpes Simplex Virus in Cerebrospinal Fluid  

PubMed Central

We have introduced a time-resolved fluorometry (TRF)-based microwell hybridization assay for PCR products in detection of herpes simplex virus (HSV) in cerebrospinal fluid (CSF) specimens. TRF is a sensitive nonradioactive detection technique which involves the use of lanthanide chelates as fluorescent labels. We used PCR primers from the glycoprotein D genes of HSV type 1 (HSV-1) and HSV-2. The biotinylated PCR products were collected on streptavidin-coated microtitration wells and hybridized with short oligonucleotide probes, europium labeled for HSV-1 and samarium labeled for HSV-2. The TRF results were obtained as counts per second and as signal-to-noise (S/N) ratios. The sensitivity of the assay was 0.1 infectious units (PFU) of HSV in CSF specimens, and the S/N values increased with the virus amount, up to 68.5 for 103 PFU of HSV-1 and to 58.5 for 103 PFU of HSV-2, allowing semiquantitation of HSV in CSF. The primers and probes recognized all the studied 48 HSV wild-type samples, with S/N ratios of 12.4 to 190 (HSV-1) and 5.1 to 248 (HSV-2). We tested CSF specimens, 100 for each HSV type, which were HSV PCR negative by Southern blot and 22 CSF specimens which were HSV-1 or -2 PCR blot positive. In the TRF test, the mean S/N ratio for the HSV-1-negative CSF was 1.37 (standard deviation [SD] = 0.513) and for the HSV-2-negative CSF it was 1.03 (SD = 0.098). The HSV-1 blot-positive CSF yielded S/N ratios of 3.6 to 85.9, and the HSV-2 blot-positive CSF yielded ratios from 1.9 to 13. Using the mean S/N ratio for negative CSF specimens + 3 SD as the cutoff yielded all the previously HSV-positive specimens as TRF positive. The TRF PCR assay for HSV in CSF specimens is a rapid and sensitive method, improves interpretation of PCR results, and is well suited for automation. PMID:10970360

Hukkanen, Veijo; Rehn, Tiina; Kajander, Ritva; Sjöroos, Minna; Waris, Matti

2000-01-01

316

Cerebrospinal fluid neurofilament light chain protein levels in subtypes of frontotemporal dementia  

PubMed Central

Background Frontotemporal dementia (FTD) is recognised as a clinically and morphologically heterogeneous group of interrelated neurodegenerative conditions. One of the subtypes within this disease spectrum is the behavioural variant FTD (bvFTD). This is known to be a varied disorder with a mixture of tau-positive and tau-negative underlying pathologies. The other subtypes include semantic dementia (SD), which generally exhibits tau-negative pathology, and progressive non-fluent aphasia (PNFA), which is usually tau-positive. As the clinical presentation of these subtypes may overlap, a specific diagnosis can be difficult to attain and today no specific biomarker can predict the underlying pathology. Neurofilament light chain protein (NFL), a cytoskeletal constituent of intermediate filaments, is thought to reflect neuronal and axonal death when appearing in the cerebrospinal fluid (CSF). NFL has been shown to be elevated in CSF in patients with FTD compared with AD and controls. Our hypothesis was that the levels of NFL also differ between the subtypes of FTD and may indicate the underlying pathological subtype. Methods We retrospectively analysed data from previous CSF analyses in 34 FTD cases (23 bvFTD, seven SD, four PNFA), 20 AD cases, and 26 healthy controls. A separate group of 10 neuropathologically verified and subtyped FTD cases (seven tau-negative, three tau-positive) were also analysed. Result NFL levels were significantly higher in FTD compared with both AD (p<0.001) and controls (p<0.001). The NFL levels of SD and bvFTD were significantly higher (p<0.001) compared with AD. The biomarker profiles of PNFA and AD were similar. In the neuropathologically verified FTD cases, NFL was higher in the tau-negative than in the tau-positive cases (exact p=0.017). Conclusions The marked NFL elevation in some but not all FTD cases is likely to reflect the different underlying pathologies. The highest NFL values found in the SD group as well as in the neuropathologically verified tau-negative cases may be of subtype diagnostic value, if corroborated in larger patient cohorts. In bvFTD, a mixture of tau-positive and tau-negative underlying pathologies could possibly explain the intermediate NFL values. PMID:23718879

2013-01-01

317

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

PubMed

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

Oreskovi?, D; Klarica, M

2010-09-24

318

Transthyretin, Thyroxine, and Retinol-Binding Protein in Human Cerebrospinal Fluid: Effect of Lead Exposure  

PubMed Central

Transthyretin (TTR), synthesized by the choroid plexus, is proposed to have a role in transport of thyroid hormones in the brain. Our previous studies in animals suggest that sequestration of lead (Pb) in the choroid plexus may lead to a marked decrease in TTR levels in the cerebrospinal fluid (CSF). The objectives of this study were to establish in humans whether TTR and thyroxine (T4) are correlated in the CSF, and whether CSF levels of Pb are associated with those of TTR, T4, and/or retinol-binding protein (RBP). Eighty-two paired CSF and blood/serum samples were collected from patients undergoing clinical diagnosis of CSF chemistry. Results showed that the mean value of CSF concentrations for TTR was 3.33 ± 1.60 ?g/mg of CSF proteins (mean ± SD, n = 82), for total T4 (TT4) was 1.56 ± 1.68 ng/mg (n = 82), for RBP was 0.34 ± 0.19 ?g/mg (n = 82), and for Pb was 0.53 ± 0.69 ?g/dl (n = 61 for those above the detection limit). Linear regression analyses revealed that CSF TTR levels were positively associated with those of CSF TT4 (r = 0.33, p < 0.005). CSF TTR concentrations, however, were inversely associated with CSF Pb concentrations (r = ?0.29, p < 0.05). There was an inverse, albeit weak, correlation between CSF TT4 and CSF Pb concentrations (r = ?0.22, p = 0.09). The concentrations of TTR, TT4, and Pb in the CSF did not vary as the function of their levels in blood or serum, but RBP concentrations in the CSF did correlate to those of serum (r = 0.39, p < 0.0005). Unlike TTR, CSF RBP concentrations were not influenced by Pb. These human data are consistent with our earlier observations in animals, which suggest that TTR is required for thyroxine transport in the CSF and that Pb exposure is likely associated with diminished TTR levels in the CSF. PMID:11294981

Zheng, Wei; Lu, Yong-Ming; Lu, Guo-Yao; Zhao, Qiuqu; Cheung, Onpan; Blaner, William S.

2014-01-01

319

Cerebrospinal Fluid (CSF) Neuronal Biomarkers across the Spectrum of HIV Infection: Hierarchy of Injury and Detection  

PubMed Central

The character of central nervous system (CNS) HIV infection and its effects on neuronal integrity vary with evolving systemic infection. Using a cross-sectional design and archived samples, we compared concentrations of cerebrospinal fluid (CSF) neuronal biomarkers in 143 samples from 8 HIV-infected subject groups representing a spectrum of untreated systemic HIV progression and viral suppression: primary infection; four groups of chronic HIV infection neuroasymptomatic (NA) subjects defined by blood CD4+ T cells of >350, 200–349, 50–199, and <50 cells/µL; HAD; treatment-induced viral suppression; and ‘elite’ controllers. Samples from 20 HIV-uninfected controls were also examined. The neuronal biomarkers included neurofilament light chain protein (NFL), total and phosphorylated tau (t-tau, p-tau), soluble amyloid precursor proteins alpha and beta (sAPP?, sAPP?) and amyloid beta (A?) fragments 1–42, 1–40 and 1–38. Comparison of the biomarker changes showed a hierarchy of sensitivity in detection and suggested evolving mechanisms with progressive injury. NFL was the most sensitive neuronal biomarker. Its CSF concentration exceeded age-adjusted norms in all HAD patients, 75% of NA CD4<50, 40% of NA CD4 50–199, and 42% of primary infection, indicating common neuronal injury with untreated systemic HIV disease progression as well as transiently during early infection. By contrast, only 75% of HAD subjects had abnormal CSF t-tau levels, and there were no significant differences in t-tau levels among the remaining groups. sAPP? and ? were also abnormal (decreased) in HAD, showed less marked change than NFL with CD4 decline in the absence of HAD, and were not decreased in PHI. The CSF A? peptides and p-tau concentrations did not differ among the groups, distinguishing the HIV CNS injury profile from Alzheimer's disease. These CSF biomarkers can serve as useful tools in selected research and clinical settings for patient classification, pathogenetic analysis, diagnosis and management. PMID:25541953

Peterson, Julia; Gisslen, Magnus; Zetterberg, Henrik; Fuchs, Dietmar; Shacklett, Barbara L.; Hagberg, Lars; Yiannoutsos, Constantin T.; Spudich, Serena S.; Price, Richard W.

2014-01-01

320

The cerebrospinal fluid proteome in HIV infection: change associated with disease severity.  

SciTech Connect

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.

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

321

Cerebrospinal Fluid (CSF) Neuronal Biomarkers across the Spectrum of HIV Infection: Hierarchy of Injury and Detection.  

PubMed

The character of central nervous system (CNS) HIV infection and its effects on neuronal integrity vary with evolving systemic infection. Using a cross-sectional design and archived samples, we compared concentrations of cerebrospinal fluid (CSF) neuronal biomarkers in 143 samples from 8 HIV-infected subject groups representing a spectrum of untreated systemic HIV progression and viral suppression: primary infection; four groups of chronic HIV infection neuroasymptomatic (NA) subjects defined by blood CD4+ T cells of >350, 200-349, 50-199, and <50 cells/µL; HAD; treatment-induced viral suppression; and 'elite' controllers. Samples from 20 HIV-uninfected controls were also examined. The neuronal biomarkers included neurofilament light chain protein (NFL), total and phosphorylated tau (t-tau, p-tau), soluble amyloid precursor proteins alpha and beta (sAPP?, sAPP?) and amyloid beta (A?) fragments 1-42, 1-40 and 1-38. Comparison of the biomarker changes showed a hierarchy of sensitivity in detection and suggested evolving mechanisms with progressive injury. NFL was the most sensitive neuronal biomarker. Its CSF concentration exceeded age-adjusted norms in all HAD patients, 75% of NA CD4<50, 40% of NA CD4 50-199, and 42% of primary infection, indicating common neuronal injury with untreated systemic HIV disease progression as well as transiently during early infection. By contrast, only 75% of HAD subjects had abnormal CSF t-tau levels, and there were no significant differences in t-tau levels among the remaining groups. sAPP? and ? were also abnormal (decreased) in HAD, showed less marked change than NFL with CD4 decline in the absence of HAD, and were not decreased in PHI. The CSF A? peptides and p-tau concentrations did not differ among the groups, distinguishing the HIV CNS injury profile from Alzheimer's disease. These CSF biomarkers can serve as useful tools in selected research and clinical settings for patient classification, pathogenetic analysis, diagnosis and management. PMID:25541953

Peterson, Julia; Gisslen, Magnus; Zetterberg, Henrik; Fuchs, Dietmar; Shacklett, Barbara L; Hagberg, Lars; Yiannoutsos, Constantin T; Spudich, Serena S; Price, Richard W

2014-01-01

322

Distribution in cerebrospinal fluid, blood, and lymph of epidurally injected morphine and inulin in dogs  

SciTech Connect

We describe procedures for catheterizing the epidural space, the azygos vein, and the thoracic lymph duct of dogs without using fluoroscopy. The success rates of the procedures were 100, 80, and 50%, respectively (n = 10). To assess the validity of the model, /sup 3/H-morphine and unlabeled morphine (2 mg) were injected epidurally in ten dogs. Lumbar cerebrospinal fluid (CSF), azygos venous blood, arterial blood, and lymph were sampled before and 5, 20, 60, 120, 180, 240, 300 and 360 min after injection. During the first 20 min, morphine levels in the azygos vein were about three and ten times greater than arterial and lymphatic levels, respectively (n = 3; P less than 0.01). Morphine levels were significantly greater in the azygos vein (n = 8) and the femoral artery (n = 10) during the first 20 and 60 min than they were later, respectively (P less than 0.05). In the lymph (n = 5), the levels of morphine at 60 min were statistically greater (P less than 0.05) than levels at 4, 5, and 6 hr. At no time were the concurrent arterial and lymph levels different from each other. In the lumbar CSF, the morphine peak concentration was reached 5-60 min after epidural injection and ranged between 5 and 93 micrograms/ml. In the CSF, the levels of morphine were significantly greater during the first 20 min than later (n = 7; P less than 0.05). The washout of the lumbar CSF curve for morphine appeared to be fitted by a two-compartment open model. The t1/2-alpha and t1/2-beta values were 14.7 +/- 7.2 min and 106 +/- 45 min, respectively (mean +/- SD). Cumulative percentages of the epidural dose of morphine passed into the azygos system within the first 5, 20, 60, and 120 min after injection were calculated to be 4.0 +/- 2.1, 23.5 +/- 14.6, 49.2 +/- 34.2, and 55.9 +/- 35.3, respectively (mean +/- SD; n = 8).

Durant, P.A.; Yaksh, T.L.

1986-06-01

323

Peptide Fingerprinting of Alzheimer's Disease in Cerebrospinal Fluid: Identification and Prospective Evaluation of New Synaptic Biomarkers  

PubMed Central

Background Today, dementias are diagnosed late in the course of disease. Future treatments have to start earlier in the disease process to avoid disability requiring new diagnostic tools. The objective of this study is to develop a new method for the differential diagnosis and identification of new biomarkers of Alzheimer's disease (AD) using capillary-electrophoresis coupled to mass-spectrometry (CE-MS) and to assess the potential of early diagnosis of AD. Methods and Findings Cerebrospinal fluid (CSF) of 159 out-patients of a memory-clinic at a University Hospital suffering from neurodegenerative disorders and 17 cognitively-healthy controls was used to create differential peptide pattern for dementias and prospective blinded-comparison of sensitivity and specificity for AD diagnosis against the Criterion standard in a naturalistic prospective sample of patients. Sensitivity and specificity of the new method compared to standard diagnostic procedures and identification of new putative biomarkers for AD was the main outcome measure. CE-MS was used to reliably detect 1104 low-molecular-weight peptides in CSF. Training-sets of patients with clinically secured sporadic Alzheimer's disease, frontotemporal dementia, and cognitively healthy controls allowed establishing discriminative biomarker pattern for diagnosis of AD. This pattern was already detectable in patients with mild cognitive impairment (MCI). The AD-pattern was tested in a prospective sample of patients (n?=?100) and AD was diagnosed with a sensitivity of 87% and a specificity of 83%. Using CSF measurements of beta-amyloid1-42, total-tau, and phospho181-tau, AD-diagnosis had a sensitivity of 88% and a specificity of 67% in the same sample. Sequence analysis of the discriminating biomarkers identified fragments of synaptic proteins like proSAAS, apolipoprotein J, neurosecretory protein VGF, phospholemman, and chromogranin A. Conclusions The method may allow early differential diagnosis of various dementias using specific peptide fingerprints and identification of incipient AD in patients suffering from MCI. Identified biomarkers facilitate face validity for the use in AD diagnosis. PMID:22046305

Zürbig, Petra; Raedler, Thomas J.; Arlt, Sönke; Kellmann, Markus; Mullen, William; Eichenlaub, Martin; Mischak, Harald; Wiedemann, Klaus

2011-01-01

324

Cerebrospinal Fluid Catecholamine Levels as Predictors of Outcome in Subarachnoid Hemorrhage  

PubMed Central

Objective Subarachnoid hemorrhage (SAH) is associated with marked sympathetic activation at the time of ictus. The purpose of this study is to determine whether early central catecholamine levels measured from cerebrospinal fluid (CSF) relate to outcome in patients with SAH. Methods Observational study of consecutive SAH grade 3–5 patients who underwent ventriculostomy placement, but did not undergo open craniotomy for aneurysm obliteration. CSF samples were obtained during the first 48 h following symptom onset and assayed for catecholamine levels. Statistical analyses were performed to determine whether the levels predicted mortality by day 15 or mortality/disability by day 30. Results For the 102 patients included, mean age was 58, and 73% were female ? 21% experienced day-15 mortality, and 32% experienced mortality/disability by day 30. Early mortality was related to Hunt-Hess (H/H) grade (p < 0.001), neurogenic cardiomyopathy (NC) (p = 0.003), cerebral infarction (p = 0.001), elevated intracranial pressure (ICP) (p = 0.029), epinephrine (EPI) level (p = 0.002) and norepinephrine/3,4-dihydroxyphenylglycol (NE/DHPG) ratio (p = 0.003). Mortality/disability was related to H/H grade (p < 0.001), NC (p = 0.018), infarction (p < 0.001), elevated ICP (p = 0.002), EPI (p = 0.004) and NE/DHPG (p = 0.014). Logistic regression identified age [OR 1.09 (95% CI 1.01–1.17)], H/H grade [9.52 (1.19–77)], infarction [10.87 (1.22–100)], ICP elevation [32.26 (2–500)], EPI [1.06 (1.01–1.10)], and (inversely) DHPG [0.99 (0.99–1.00)] as independent predictors of early mortality. For mortality/disability, H/H grade [OR 21.74 (95% CI 5.62?83)], ICP elevation [18.52 (1.93–166)], and EPI [1.05 (1.02–1.09)] emerged as independent predictors. Proportional-hazards analysis revealed age [HR 1.041 (95% CI 1.003–1.08)], H/H grade [6.9 (1.54–31.25)], NC [4.31 (1.5–12.35)], and EPI [1.032 (1.009–1.054)] independently predicted early mortality. Conclusions CSF catecholamine levels are elevated in SAH patients who experience early mortality or disability. EPI may potentially serve as useful index of outcome in this population of patients with SAH. PMID:22222551

Moussouttas, Michael; Huynh, Thanh T.; Khoury, John; Lai, Edwin W.; Dombrowski, Keith; Pello, Scott; Pacak, Karel

2012-01-01

325

Delayed presentation of late-onset cerebrospinal fluid rhinorrhoea following dopamine agonist therapy for giant prolactinoma  

PubMed Central

Summary Therapeutic shrinkage of prolactinomas with dopamine agonists achieves clinical benefit but can expose fistulae that have arisen as a result of bony erosion of the sella floor and anterior skull base by the invasive tumour, resulting in the potential development of cerebrospinal fluid (CSF) rhinorrhoea, meningitis, and rarely pneumocephalus. Onset of symptoms is typically within 4 months of commencing therapy. The management is typically surgical repair via an endoscopic transnasal transsphenoidal approach. A 23-year-old man presented to the Emergency Department with acute left limb weakness and intermittent headaches. Visual fields were full to confrontation. Immediate computed tomography and subsequent magnetic resonance imaging (MRI), demonstrated a 5?cm lobular/cystic mass invading the right cavernous sinus, displacing and compressing the midbrain, with destruction of the bony sella. He was referred to the regional pituitary multidisciplinary team (MDT). Serum prolactin was 159?455?mIU/l (7514.37?ng/ml) (normal ranges 100–410?mIU/l (4.72–19.34?ng/ml)). Cabergoline was commenced causing dramatic reduction in tumour size and resolution of neurological symptoms. Further dose titrations were required as the prolactin level plateaued and significant residual tumour remained. After 13 months of treatment, he developed continuous daily rhinorrhea, and on presenting to his general practitioner was referred to an otolaryngologist. When next seen in the routine regional pituitary clinic six-months later he was admitted for urgent surgical repair. Histology confirmed a prolactinoma with a low proliferation index of 2% (Ki-67 antibody). In view of partial cabergoline resistance he completed a course of conventional radiotherapy. Nine months after treatment the serum prolactin had fallen to 621?mIU/l, and 12 months after an MRI showed reduced tumour volume. Learning points CSF rhinorrhoea occurred 13 months after the initiation of cabergoline, suggesting a need for vigilance throughout therapy.Dedicated bony imaging should be reviewed early in the patient pathway to assess the potential risk of CSF rhinorrhoea after initiation of dopamine agonist therapy.There was a significant delay before this complication was brought to the attention of the regional pituitary MDT, with associated risk whilst left untreated. This demonstrates a need for patients and healthcare professionals to be educated about early recognition and management of this complication to facilitate timely and appropriate referral to the MDT for specialist advice and management. We changed our nurse-led patient education programme as a result of this case.An excellent therapeutic response was achieved with conventional radiotherapy after limited surgery having developed partial cabergoline resistance and CSF rhinorrhoea. PMID:25520847

Prague, J K; Ward, C L; Mustafa, O G; King, A; Thomas, N W; Gilbert, J

2014-01-01

326

Low neuropeptide Y in cerebrospinal fluid in bipolar patients is associated with previous and prospective suicide attempts.  

PubMed

The attempted and accomplished suicide rates in patients with bipolar disorder are 40-50% and 15-20%, respectively. No biological markers that help predict suicide been identified. Human and experimental animal data indicate that dysregulation of the neuropeptide Y (NPY) system plays a role in depression, anxiety, and posttraumatic stress disorder (PTSD). The aim of this study was to explore if low cerebrospinal fluid (CSF) NPY is associated with (1) past suicide attempts, (2) future suicide attempts, and (3) trait anxiety. Lumbar puncture was performed on 120 clinically stable patients with bipolar disorder enrolled in the St Göran Bipolar Project, where the number of previous suicide attempts was documented. NPY-like immunoreactivity (NPY-LI) was determined in cerebrospinal fluid (CSF). Patients were reexamined one year after the lumbar puncture and suicide attempts were recorded. NPY-LI was significantly lower in patients with a history of suicide attempt than in patients who had not attempted suicide prior to lumbar puncture. Importantly, NPY-LI was markedly lower in patients who made a suicide attempt during the follow-up period compared to patients who did not. Patients who attempted suicide during the follow-up also had markedly lower NPY-LI than those with previous suicide attempts who did not reattempt. Our results suggest that low CSF NPY-LI predicts future suicide attempts. The data are in line with the hypothesis that NPY signaling is altered in affective disorders and states of emotional dysregulation. PMID:25453484

Sandberg, Johan V; Jakobsson, Joel; Pålsson, Erik; Landén, Mikael; Mathé, Aleksander A

2014-12-01

327

Markers of glutamate signaling in cerebrospinal fluid and serum from patients with bipolar disorder and healthy controls.  

PubMed

Glutamate is the major excitatory neurotransmitter in the brain. Aberrations in glutamate signaling have been linked to the pathophysiology of mood disorders. Increased plasma levels of glutamate as well as higher glutamine+glutamate levels in the brain have been demonstrated in patients with bipolar disorder as compared to healthy controls. In this study, we explored the glutamate hypothesis of bipolar disorder by examining peripheral and central levels of amino acids related to glutamate signaling. A total of 215 patients with bipolar disorder and 112 healthy controls from the Swedish St. Göran bipolar project were included in this study. Glutamate, glutamine, glycine, l-serine and d-serine levels were determined in serum and in cerebrospinal fluid using high performance liquid chromatography with fluorescence detection. Serum levels of glutamine, glycine and d-serine were significantly higher whereas l-serine levels were lower in patients with bipolar disorder as compared to controls. No differences between the patient and control group in amino acid levels were observed in cerebrospinal fluid. The observed differences in serum amino acid levels may be interpreted as a systemic aberration in amino acid metabolism that affects several amino acids related to glutamate signaling. PMID:25482684

Pålsson, Erik; Jakobsson, Joel; Södersten, Kristoffer; Fujita, Yuko; Sellgren, Carl; Ekman, Carl-Johan; Ågren, Hans; Hashimoto, Kenji; Landén, Mikael

2015-01-01

328

Follow-Up Investigations of Tau Protein and S-100B Levels in Cerebrospinal Fluid of Patients with Creutzfeldt-Jakob Disease  

Microsoft Academic Search

Background: S-100B and tau protein have a high differential diagnostic potential for the diagnosis of Creutzfeldt-Jakob disease (CJD). So far there has been only limited information available about the dynamics of these parameters in the cerebrospinal fluid (CSF). However, there is a special interest in finding biochemical markers to monitor disease progression for differential diagnosis and treatment. Patients and Methods:

Lukas Cepek; Petra Steinacker; Brit Mollenhauer; Birgitt Wiese; Barbara Ciesielczyk; Mirko Bibl; Jens Wiltfang; Inga Zerr; Walter Schulz-Schaeffer; Hans A. Kretzschmar; Sigrid Poser; Markus Otto

2005-01-01

329

Cerebrospinal fluid outflow resistance measurements in the selection of patients for shunt surgery in the normal pressure hydrocephalus syndrome. A controlled trial  

Microsoft Academic Search

Summary In an attempt to determine to what extent the measurement of cerebrospinal fluid (CSF) outflow resistance (Rout) can distinguish patients with normal-pressure hydrocephalus (NPH) who respond to shunt surgery from patients who fail to do so, the authors undertook a controlled trial. Eighteen patients with the diagnosis of NPH entered the study. In connection with the shunt operation all

M. Kosteljanetz; A.-M. Nehen; J. Kaalund

1990-01-01

330

5-hydroxyindoleacetic acid (and homovanillic acid) levels in the cerebrospinal fluid after probenecid application in patiens with manic-depressive psychosis  

Microsoft Academic Search

Probenecid was administered to 17 depressed, 19 manic and 15 control patients and further to 11 healthy volunteers. Before and after the administration the levels of 5-hydroxyindoleacetic acid (5-HIAA) were determined in cerebrospinal fluid (CSF). In six of the depressed, seven of the manic and seven of the patients from the group of controls and volunteers also homovanillic acid (HVA)

B. E. Roos; R. Sjöström

1969-01-01

331

Role of Interpeduncular and Prepontine Cistern Cerebrospinal Fluid Flow Measurements in Prediction of Endoscopic Third Ventriculostomy Success in Pediatric Triventricular Hydrocephalus  

Microsoft Academic Search

Aim: The aim of the present study was to evaluate the correlation of the clinical success of the endoscopic third ventriculostomy (ETV) procedure with the measurements of cerebrospinal fluid (CSF) flow through the interpeduncular and prepontine cisterns in pediatric triventricular hydrocephalus. Methods: 51 children (age range: 25–201 months; mean: 55.3 months) with primary aqueductal stenosis who have been treated with

Ihsan Anik; Volkan Etus; Yonca Anik; Savas Ceylan

2010-01-01

332

New method for the extraction of viral RNA and DNA from cerebrospinal fluid for use in the polymerase chain reaction assay  

Microsoft Academic Search

A new, rapid, and simple method for the isolation of either RNA or DNA from cerebrospinal fluid samples for subsequent amplification by specific polymerase chain reaction (PCR) assays is described. The technique involves a single extraction with a guanidinium thiocyanate acid (GuSCN) buffer, and does not require the use of organic solvents. Applied to the recovery of enteroviral RNA, herpes

I. Casas; L. Powell; P. E. Klapper; G. M. Cleator

1995-01-01

333

Affinity depletion of albumin from human cerebrospinal fluid using Cibacron-blue-3G-A-derivatized photopatterned copolymer in a microfluidic device  

Microsoft Academic Search

In the context of proteomic research, affinity separations for the prefractionation of complex mixtures, such as cell lysates or human tissues, have become increasingly important. Microfluidic devices have shown significant potential to achieve fast analysis and low sample consumption. Here, we demonstrate the use of a microfluidic device to achieve affinity capture of albumin from human cerebrospinal fluid. Traditional photolithography

Chen Li; Kelvin H. Lee

2004-01-01

334

Metronidazole and Hydroxymetronidazole Central Nervous System Distribution: 2. Cerebrospinal Fluid Concentration Measurements in Patients with External Ventricular Drain  

PubMed Central

This study explored metronidazole and hydroxymetronidazole distribution in the cerebrospinal fluid (CSF) of brain-injured patients. Four brain-injured patients with external ventricular drain received 500 mg of metronidazole over 0.5 h every 8 h. CSF and blood samples were collected at steady state over 8 h, and the metronidazole and hydroxymetronidazole concentrations were assayed by high-pressure liquid chromatograph. A noncompartmental analysis was performed. Metronidazole is distributed extensively within CSF, with a mean CSF to unbound plasma AUC0–? ratio of 86% ± 16%. However, the concentration profiles in CSF were mostly flat compared to the plasma profiles. Hydroxymetronidazole concentrations were much lower than those of metronidazole both in plasma and in CSF, with a corresponding CSF/unbound plasma AUC0–? ratio of 79% ± 16%. We describe here for the first time in detail the pharmacokinetics of metronidazole and hydroxymetronidazole in CSF. PMID:24277050

Frasca, Denis; Dahyot-Fizelier, Claire; Adier, Christophe; Mimoz, Olivier; Debaene, Bertrand; Couet, William

2014-01-01

335

Role of cerebrospinal fluid IL-8 as a marker for differentiation between acute bacterial and aseptic meningitis.  

PubMed

No doubt, the distinguishing between bacterial and aseptic meningitis in the emergency department could help to limit unnecessary antibiotic use and hospital admissions. This study evaluated the role of cerebrospinal fluid IL-8 in differentiating acute bacterial meningitis (ABM) from aseptic meningitis (AM). A total of 80 hospitalized patients with clinical presentations of suspected acute meningitis were subjected to estimation of IL-8 CSF concentrations. The results showed that CSF IL-8 levels were higher in acute bacterial meningitis than in aseptic ones (p < 0.05). The best cut-off value of CSF IL8 for early diagnosis of bacterial meningitis was 3.6 ng/ml with a sensitivity of 82.5% and a specificity of 85.0%. PMID:24961026

Abdelmoez, Amal Tohamy; Zaky, Doaa Zakaria; Maher, Amany M

2014-04-01

336

Changes in Protein Level in the Cerebrospinal Fluid of a Patient with Cerebral Radiation Necrosis Treated with Bevacizumab  

PubMed Central

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

Yano, Hirohito; Nakayama, Noriyuki; Morimitsu, Kasumi; Futamura, Manabu; Ohe, Naoyuki; Miwa, Kazuhiro; Shinoda, Jun; Iwama, Toru

2014-01-01

337

High-performance liquid chromatographic measurement of cerebrospinal fluid tetrahydrobiopterin, neopterin, homovanillic acid and 5-hydroxindoleacetic acid in neurological diseases.  

PubMed

Cerebrospinal fluid (CSF) samples from patients with a variety of neurological disorders were assayed to determine the concentrations of tetrahydrobiopterin (BH4), the active cofactor of hydroxylases. Dihydroneopterin (NH2) and neopterin (N), which are linked with BH4 synthesis and are inflammatory biochemical markers, were also measured simultaneously in a number of patients. 5-Hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), the main products of serotonin and dopamine breakdown, were analyzed in parallel whenever possible. As BH4 and NH2 are difficult to analyze owing to their instability, CSF samples were collected under special conditions to preserve the reduced BH4 and NH2. Liquid chromatographic assays and detection of the various substances measured also required particular precautions. BH4 concentrations were elevated in patients with neurological disorders such as syphilis and lupus-like disease and especially in an AIDS patient with neurological complications with an increased N/BH4 ratio. PMID:7524948

Candito, M; Nagatsu, T; Chambon, P; Chatel, M

1994-07-01

338

[Reassessment of a combination of cerebrospinal fluid scintigraphy and nasal pledget counts in patients with suspected rhinorrhea].  

PubMed

A combination study of cerebrospinal fluid scintigraphy and nasal pledget counts was performed using 37 MBq of 111In-DTPA in 12 patients with suspected rhinorrhea. A pledget was inserted and dwelled in each nasal cavity for 6 hours, with the patient prone during at least 30 minutes. A total of 18 studies was implemented and nasal pledget counting method successfully diagnosed all of CSF rhinorrhea. Diagnosis was possible when pledget counts were greater than 1 kcpm. In patients with persistent, intermittent and occult/no nasal discharge, rhinorrhea was found in 100% (5/5), 60% (3/5), 25% (2/8), respectively. Two cases only exhibited positive scintigraphy. MRI or CT cisternography should be first performed in patients with persistent discharge, but in patients with intermittent/occult discharge pledget counting method might take priority of other diagnostic modalities. In conclusion, nasal pledget counting method is a simple and useful tool for detecting rhinorrhea. PMID:9753923

Kosuda, S; Arai, S; Hohshito, Y; Tokumitsu, H; Kusano, S; Ishihara, S; Shima, K

1998-07-01

339

Calprotectin and lactoferrin in the cerebrospinal fluid; biomarkers utilisable for differential diagnostics of bacterial and aseptic meningitis?  

PubMed

Abstract Background: The aim of our work was to assess the diagnostic contribution of calprotectin and lactoferrin determinations in the cerebrospinal fluid when distinguishing between bacterial and aseptic meningitides. Methods: In 23 patients with bacterial meningitis (BM) and in 50 patients with aseptic meningitis (AM), we determined the concentrations of calprotectin, lactoferrin and the conventional biomarkers like glucose, total protein, lactate and polynuclear count in the cerebrospinal fluid (CSF). The discriminative power of the various parameters studied was determined by means of receiver operating characteristic (ROC) curves: the area under the curve (AUC), sensitivity, specificity, the positive likelihood ratio (+LR), and the negative likelihood ratio (-LR). Results: The diagnostic efficiency of calprotectin, lactoferrin, lactate, and polynuclear count when distinguishing between bacterial and aseptic meningitides, expressed by ROC curve parameters, was as follows: AUC (0.736, 0.946, 0.932, 0.932), sensitivity (86.2, 96.6, 90.0, 89.7), specificity (58.5, 92.4, 87.0, 90.6), +LR (2.08, 12.8, 6.9, 9.50), -LR (0.24, 0.04, 0.11, 0.11), respectively. The optimal cut point for calprotectin and lactoferrin was 191 ng/mL and 17.8 ng/mL, respectively. Conclusions: Our findings show, that the determination of lactoferrin in the CSF was diagnostically the most efficient marker in distinguishing between bacterial and viral meningitides. Calprotectin was far less efficient diagnostic marker. The polynuclear count and lactate concentration showed a very good diagnostic efficiency as well. The determination of protein and glucose was diagnostically less beneficial. PMID:25405719

Dastych, Milan; Gottwaldová, Jana; Cermáková, Zdenka

2014-11-18

340

Benefit of cerebrospinal fluid spectrophotometry in the assessment of CT scan negative suspected subarachnoid haemorrhage: A diagnostic accuracy study.  

PubMed

This study aimed to determine if performing cerebrospinal fluid spectrophotometry in addition to visual inspection detects more ruptured cerebral aneurysms than performing cerebrospinal fluid visual inspection alone in patients with a normal head CT scan but suspected of suffering an aneurysmal subarachnoid haemorrhage (SAH). We performed a single-centre retrospective study of patients presenting to the emergency department of a tertiary hospital who underwent both head CT scan and lumbar puncture to exclude SAH. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of an approach utilising both spectrophotometry and visual inspection (combined approach) was compared to visual inspection alone. A total of 409 patients (mean age 37.8years, 56.2% female) were recruited and six (1.5%) had a cerebral aneurysm on angiography. The sensitivity of visual inspection was 50% (95% confidence interval [CI]: 12.4-82.6%), specificity was 99% (95% CI: 97.5-99.7%), PPV was 42.9% (95% CI: 10.4-81.3%) and NPV was 99.2% (95% CI: 97.8-99.8%). The combined approach had a sensitivity of 100% (95% CI: 54.1-100%), specificity of 79.7% (95% CI: 75.4-83.5%), PPV of 6.8% (95% CI: 2.6-14.3%) and a NPV of 100% (95% CI: 98.8-100%). The sensitivity of the combined approach was not significantly different to that of visual inspection alone (p=0.25). Visual inspection had a significantly higher specificity than the combined approach (p<0.01). The combined approach detected more cases of aneurysmal SAH than visual inspection alone, however the difference in sensitivity was not statistically significant. Visual xanthochromia should prompt angiography because of a superior specificity and PPV. Due to its reduced sensitivity, caution should be applied when using only visual inspection of the supernatant. PMID:25439758

Hann, Angus; Chu, Kevin; Greenslade, Jaimi; Williams, Julian; Brown, Anthony

2015-01-01

341

Cerebrospinal fluid levels of inflammation, oxidative stress and NAD+ are linked to differences in plasma carotenoid concentrations  

PubMed Central

Background The consumption of foods rich in carotenoids that possess significant antioxidant and inflammatory modulating properties has been linked to reduced risk of neuropathology. The objective of this study was to evaluate the relationship between plasma carotenoid concentrations and plasma and cerebrospinal fluid (CSF) markers of inflammation, oxidative stress and nicotinamide adenine dinucleotide (NAD+) in an essentially healthy human cohort. Methods Thirty-eight matched CSF and plasma samples were collected from consenting participants who required a spinal tap for the administration of anaesthetic. Plasma concentrations of carotenoids and both plasma and cerebrospinal fluid (CSF) levels of NAD(H) and markers of inflammation (IL-6, TNF-?) and oxidative stress (F2-isoprostanes, 8-OHdG and total antioxidant capacity) were quantified. Results The average age of participants was 53 years (SD?=?20, interquartile range?=?38). Both ?-carotene (P?=?0.01) and ?-carotene (P?

2014-01-01

342

An integrated mechanism of pediatric pseudotumor cerebri syndrome: evidence of bioenergetic and hormonal regulation of cerebrospinal fluid dynamics.  

PubMed

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

Sheldon, Claire A; Kwon, Young Joon; Liu, Grant T; McCormack, Shana E

2015-02-01

343

The Influence of Body Position on Cerebrospinal Fluid Pressure Gradient and Movement in Cats with Normal and Impaired Craniospinal Communication  

PubMed Central

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

Radoš, Milan; Erceg, Gorislav; Petoši?, Antonio; Jurjevi?, Ivana

2014-01-01

344

The influence of body position on cerebrospinal fluid pressure gradient and movement in cats with normal and impaired craniospinal communication.  

PubMed

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

Klarica, Marijan; Radoš, Milan; Erceg, Gorislav; Petoši?, Antonio; Jurjevi?, Ivana; Oreškovi?, Darko

2014-01-01

345

In-depth Exploration of Cerebrospinal Fluid by Combining Peptide Ligand Library Treatment and Label-free Protein Quantification*  

PubMed Central

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

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

346

[Analysis of middle molecules in the cerebrospinal fluid of uremic patients].  

PubMed

The pathogenesis of the uraemic polyneuro-encephalopathy is unclear. Among the many possible factors also accumulations of certain medium molecule fractions of peptides and disturbances of the tryptophan metabolism shall play a role. Of 8 deceased conservatively treated uraemics and 4 patients of the chronic haemodialysis programme with a dementia of dialysis serum and postmortally got cerebrospinal liquor underwent a medium molecule fractioning. While in the liquor of normal persons no medium molecules could be proved, these substances were found in the liquor of uraemics in a nearly serum-identical pattern with clearly reduced concentrations. First of all their provenience by a toxically injured blood liquor barrier is to be explained. In contrast to the control values only conservatively treated uraemics showed significantly increased tryptophan concentrations in the liquor. However, the tryptophan concentrations of the patients with dementia were within the normal area. PMID:7342520

Sperschneider, H; Spustova, V; Stein, G; Dzurik, R

1981-12-01

347

In-depth Characterization of the Cerebrospinal Fluid (CSF) Proteome Displayed Through the CSF Proteome Resource (CSF-PR)*  

PubMed Central

In this study, the human cerebrospinal fluid (CSF) proteome was mapped using three different strategies prior to Orbitrap LC-MS/MS analysis: SDS-PAGE and mixed mode reversed phase-anion exchange for mapping the global CSF proteome, and hydrazide-based glycopeptide capture for mapping glycopeptides. A maximal protein set of 3081 proteins (28,811 peptide sequences) was identified, of which 520 were identified as glycoproteins from the glycopeptide enrichment strategy, including 1121 glycopeptides and their glycosylation sites. To our knowledge, this is the largest number of identified proteins and glycopeptides reported for CSF, including 417 glycosylation sites not previously reported. From parallel plasma samples, we identified 1050 proteins (9739 peptide sequences). An overlap of 877 proteins was found between the two body fluids, whereas 2204 proteins were identified only in CSF and 173 only in plasma. All mapping results are freely available via the new CSF Proteome Resource (http://probe.uib.no/csf-pr), which can be used to navigate the CSF proteome and help guide the selection of signature peptides in targeted quantitative proteomics. PMID:25038066

Guldbrandsen, Astrid; Vethe, Heidrun; Farag, Yehia; Oveland, Eystein; Garberg, Hilde; Berle, Magnus; Myhr, Kjell-Morten; Opsahl, Jill A.; Barsnes, Harald; Berven, Frode S.

2014-01-01

348

Comparison of Methods for miRNA Extraction from Plasma and Quantitative Recovery of RNA from Cerebrospinal Fluid  

PubMed Central

Interest in extracellular RNA (exRNA) has intensified as evidence accumulates that these molecules may be useful as indicators of a wide variety of biological conditions. To establish specific exRNA molecules as clinically relevant biomarkers, reproducible recovery from biological samples and reliable measurements of the isolated RNA are paramount. Toward these ends, careful and rigorous comparisons of technical procedures are needed at all steps from sample handling to RNA isolation to RNA measurement protocols. In the investigations described in this methods paper, RT-qPCR was used to examine the apparent recovery of specific endogenous miRNAs and a spiked-in synthetic RNA from blood plasma samples. RNA was isolated using several widely used RNA isolation kits, with or without the addition of glycogen as a carrier. Kits examined included total RNA isolation systems that have been commercially available for several years and commonly adapted for extraction of biofluid RNA, as well as more recently introduced biofluids-specific RNA methods. Our conclusions include the following: some RNA isolation methods appear to be superior to others for the recovery of RNA from biological fluids; addition of a carrier molecule seems to be beneficial for some but not all isolation methods; and quantitative recovery of RNA is observed from increasing volumes of cerebrospinal fluid. PMID:23720669

McAlexander, Melissa A.; Phillips, Maggie J.; Witwer, Kenneth W.

2013-01-01

349

Age-Dependent Changes in the Cerebrospinal Fluid Proteome by Slow Off-Rate Modified Aptamer Array  

PubMed Central

An important precondition for the successful development of diagnostic assays of cerebrospinal fluid (CSF) biomarkers of age-related neurodegenerative diseases is an understanding of the dynamic nature of the CSF proteome during the normal aging process. In this study, a novel proteomic technology was used to quantify hundreds of proteins simultaneously in the CSF from 90 cognitively normal adults 21 to 85 years of age. SomaLogic's highly multiplexed proteomic platform can measure more than 800 proteins simultaneously from small volumes of biological fluids using novel slow off-rate modified aptamer (SOMAmer) protein affinity reagents with sensitivity, specificity, and dynamic ranges that meet or exceed those of enzyme-linked immunosorbent assays. In the first application of this technology to CSF, we detected 248 proteins that possessed signals greater than twofold over background. Several novel correlations between detected protein concentrations and age were discovered that indicate that both inflammation and response to injury in the central nervous system may increase with age. Applying this powerful proteomic approach to CSF provides potential new insight into the aging of the human central nervous system that may have utility in discovering new disease-related changes in the CSF proteome. PMID:22122984

Baird, Geoffrey S.; Nelson, Sally K.; Keeney, Tracy R.; Stewart, Alex; Williams, Stephen; Kraemer, Stephan; Peskind, Elaine R.; Montine, Thomas J.

2012-01-01

350

Protein changes in immunodepleted cerebrospinal fluid from transgenic mouse models of Alexander disease detected using mass spectrometry  

PubMed Central

Cerebrospinal fluid (CSF) is a low protein content biological fluid with dynamic range spanning at least nine orders of magnitude in protein content and is in direct contact with the brain. A modified IgY-14 immunodepletion treatment was performed to enhance analysis of the low volumes of CSF that are obtainable from mice. As a model system in which to test this approach, we utilized transgenic mice that over-express the intermediate filament glial fibrillary acidic protein (GFAP). These mice are models for Alexander disease (AxD), a severe leukodystrophy in humans. From the CSF of control and transgenic mice we report the identification of 289 proteins, with relative quantification of 103 proteins. Biological and technical triplicates were performed to address animal variability as well as reproducibility in mass spectrometric analysis. Relative quantitation was performed using distributive normalized spectral abundance factor (dNSAF) spectral counting analysis. A panel of biomarker proteins with significant changes in the CSF of GFAP transgenic mice has been identified with validation from ELISA and microarray data, demonstrating the utility of our methodology and providing interesting targets for future investigations on the molecular and pathological aspects of AxD. PMID:23272901

Cunningham, Robert; Jany, Paige; Messing, Albee; Li, Lingjun

2013-01-01

351

Protein changes in immunodepleted cerebrospinal fluid from a transgenic mouse model of Alexander disease detected using mass spectrometry.  

PubMed

Cerebrospinal fluid (CSF) is a low protein content biological fluid with a dynamic range spanning at least 9 orders of magnitude in protein content and is in direct contact with the brain. A modified IgY-14 immunodepletion treatment was performed to enhance analysis of the low volumes of CSF that are obtainable from mice. As a model system in which to test this approach, we utilized transgenic mice that overexpress the intermediate filament glial fibrillary acidic protein (GFAP). These mice are models for Alexander disease (AxD), a severe leukodystrophy in humans. From the CSF of control and transgenic mice we report the identification of 289 proteins, with relative quantification of 103 proteins. Biological and technical triplicates were performed to address animal variability as well as reproducibility in mass spectrometric analysis. Relative quantitation was performed using distributive normalized spectral abundance factor (dNSAF) spectral counting analysis. A panel of biomarker proteins with significant changes in the CSF of GFAP transgenic mice has been identified with validation from enzyme-linked immunosorbent assay (ELISA) and microarray data, demonstrating the utility of our methodology and providing interesting targets for future investigations on the molecular and pathological aspects of AxD. PMID:23272901

Cunningham, Robert; Jany, Paige; Messing, Albee; Li, Lingjun

2013-02-01

352

Rapid and Sensitive RT-QuIC Detection of Human Creutzfeldt-Jakob Disease Using Cerebrospinal Fluid.  

PubMed

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

Orrú, Christina D; Groveman, Bradley R; Hughson, Andrew G; Zanusso, Gianluigi; Coulthart, Michael B; Caughey, Byron

2015-01-01

353

Gray-white matter and cerebrospinal fluid volume differences in children with Specific Language Impairment and/or Reading Disability.  

PubMed

We studied gray-white matter and cerebrospinal fluid (CSF) alterations that may be critical for language, through an optimized voxel-based morphometry evaluation in children with Specific Language Impairment (SLI), compared to Typical Language Development (TLD). Ten children with SLI (8;5-10;9) and 14 children with TLD (8;2-11;8) participated. They received a comprehensive language and reading test battery. We also analyzed a subgroup of six children with SLI+RD (Reading Disability). Brain images from 3-Tesla MRIs were analyzed with intelligence, age, gender, and total intracranial volume as covariates. Children with SLI or SLI+RD exhibited a significant lower overall gray matter volume than children with TLD. Particularly, children with SLI showed a significantly lower volume of gray matter compared to children with TLD in the right postcentral parietal gyrus (BA4), and left and right medial occipital gyri (BA19). The group with SLI also exhibited a significantly greater volume of gray matter in the right superior occipital gyrus (BA19), which may reflect a brain reorganization to compensate for their lower volumes at medial occipital gyri. Children with SLI+RD, compared to children with TLD, showed a significantly lower volume of: (a) gray matter in the right postcentral parietal gyrus; and (b) white matter in the right inferior longitudinal fasciculus (RILF), which interconnects the temporal and occipital lobes. Children with TLD exhibited a significantly lower CSF volume than children with SLI and children with SLI+RD respectively, who had somewhat smaller volumes of gray matter allowing for more CSF volume. The significant lower gray matter volume at the right postcentral parietal gyrus and greater cerebrospinal fluid volume may prove to be unique markers for SLI. We discuss the association of poor knowledge/visual representations and language input to brain development. Our comorbid study showed that a significant lower volume of white matter in the right inferior longitudinal fasciculus may be unique to children with SLI and Reading Disability. It was significantly associated to reading comprehension of sentences and receptive language composite z-score, especially receptive vocabulary and oral comprehension of stories. PMID:24418156

Girbau-Massana, Dolors; Garcia-Marti, Gracian; Marti-Bonmati, Luis; Schwartz, Richard G

2014-04-01

354

Rapid and Sensitive RT-QuIC Detection of Human Creutzfeldt-Jakob Disease Using Cerebrospinal Fluid  

PubMed Central

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

Orrú, Christina D.; Groveman, Bradley R.; Hughson, Andrew G.; Zanusso, Gianluigi; Coulthart, Michael B.

2015-01-01

355

Effect of anatomical fine structure on the flow of cerebrospinal fluid in the spinal subarachnoid space.  

SciTech Connect

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.

Stockman, Harlan Wheelock

2005-01-01

356

Maturational differences in acetazolamide-altered pH and HCO3 of choroid plexus, cerebrospinal fluid, and brain.  

PubMed

The carbonic anhydrase inhibitor acetazolamide is useful for analyzing ion transport, pH regulation, and fluid formation in developing central nervous system. We used the 14C-labeled dimethadione technique to measure alterations in steady-state pH, and to estimate the HCO3 concentration [HCO3], in choroid plexus (CP), cerebrospinal fluid (CSF), and cerebral cortex of 1- and 3-wk-old Sprague-Dawley rats treated with acetazolamide or probenecid. These drugs can suppress transport of HCO3 and other anions in some cells, consequently altering intracellular pH. In 1-wk-old infant rats whose CSF secretory process is incompletely developed, 1 h of acetazolamide treatment did not significantly change CP intracellular pH or [HCO3]. However, in 3-wk-old rats, in which the ability of CP to secrete ions and fluids is almost fully developed, acetazolamide caused marked increases in CP cell intracellular pH and [HCO3]. In contrast, acetazolamide-induced alkalinization was not observed in CSF or cerebral cortex of the 1- and 3-wk-old animals. The other test agent, probenecid (an inhibitor of anion transport but not of carbonic anhydrase), did not alter the pH of any region at any age investigated. Overall, the results are interpreted in light of developmental changes in carbonic anhydrase and previous findings from kinetic analyses of ion-translocating systems in CP. Acetazolamide may interfere with a CP apical membrane HCO3 extrusion mechanism not fully operational in infant rats. PMID:1590485

Johanson, C E; Parandoosh, Z; Dyas, M L

1992-05-01

357

Glycoprotein 330\\/Megalin: Probable Role in Receptor-Mediated Transport of Apolipoprotein J Alone and in a Complex with Alzheimer Disease Amyloid beta at the Blood-Brain and Blood-Cerebrospinal Fluid Barriers  

Microsoft Academic Search

A soluble form of Alzheimer disease amyloid beta -protein (sAbeta ) is transported in the blood and cerebrospinal fluid mainly complexed with apolipoprotein J (apoJ). Using a well-characterized in situ perfused guinea pig brain model, we recently obtained preliminary evidence that apoJ facilitates transport of sAbeta 1-40-apoJ complexes across the blood-brain barrier and the blood-cerebrospinal fluid barrier, but the mechanisms

Berislav V. Zlokovic; Cynthia L. Martel; Etsuro Matsubara; J. Gordon McComb; Gang Zheng; Robert T. McCluskey; Blas Frangione; Jorge Ghiso

1996-01-01

358

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

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

Vallabhaneni V. Rao; Julie L. Dahlheimer; Mark E. Bardgett; Abraham Z. Snyder; Rick A. Finch; Alan C. Sartorelli; David Piwnica-Worms

1999-01-01

359

Supine Digital Subtraction Myelography for the Demonstration of a Dorsal Cerebrospinal Fluid Leak in a Patient with Spontaneous Intracranial Hypotension: A Technical Note  

PubMed Central

A patient with spontaneous intracranial hypotension due to a spinal cerebrospinal fluid (CSF) leak required localization of the leakage site prior to surgical management. Conventional, computed tomography and prone digital subtraction myelography failed to localize the dural tear, which was postulated to be dorsally located. We present here a digital subtraction myelographic approach to accurately localize a dorsal site of CSF leakage by injecting iodinated contrast via a lumbar drain with the patient in the supine position. PMID:23378882

Carstensen, Michael; Chaudhary, Navjot; Leung, Andrew; Ng, Wai

2012-01-01

360

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

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

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

361

Organohalogen contaminants and metabolites in cerebrospinal fluid and cerebellum gray matter in short-beaked common dolphins and Atlantic white-sided dolphins from the western North Atlantic  

Microsoft Academic Search

Concentrations of several congeners and classes of organohalogen contaminants (OHCs) and\\/or their metabolites, namely organochlorine pesticides (OCs), polychlorinated biphenyls (PCBs), hydroxylated-PCBs (OH-PCBs), methylsulfonyl-PCBs (MeSO2-PCBs), polybrominated diphenyl ether (PBDE) flame retardants, and OH-PBDEs, were measured in cerebrospinal fluid (CSF) of short-beaked common dolphins (n = 2), Atlantic white-sided dolphins (n = 8), and gray seal (n = 1) from the western North Atlantic. In three Atlantic white-sided

Eric W. Montie; Christopher M. Reddy; Wouter A. Gebbink; Katie E. Touhey; Mark E. Hahn; Robert J. Letcher

2009-01-01

362

Ventricular cerebrospinal fluid lactate is increased in chronic fatigue syndrome compared with generalized anxiety disorder: an in vivo 3.0 T 1H MRS imaging studyy  

Microsoft Academic Search

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 T1-weighted volumetric MRI data and cerebrospinal fluid (CSF) lactate concentrations measured by proton MRS imaging (1H MRSI) in 16 subjects with CFS (modified US Centers

Sanjay J. Mathew; Xiangling Mao; Kathryn A. Keegan; Susan M. Levine; Eric L. P. Smith; Linda A. Heier; Viktor Otcheretkoa; Jeremy D. Copland; Dikoma C. Shungu

363

Bone marrow stromal cells infused into the cerebrospinal fluid promote functional recovery of the injured rat spinal cord with reduced cavity formation  

Microsoft Academic Search

The effects of bone marrow stromal cells (BMSCs) on the repair of injured spinal cord and on the behavioral improvement were studied in the rat. The spinal cord was injured by contusion using a weight-drop at the level of T8-9, and the BMSCs from the bone marrow of the same strain were infused into the cerebrospinal fluid (CSF) through the

Masayoshi Ohta; Yoshihisa Suzuki; Toru Noda; Yoko Ejiri; Mari Dezawa; Kazuya Kataoka; Hirotomi Chou; Namiko Ishikawa; Naoya Matsumoto; Yasushi Iwashita; Eiji Mizuta; Sadako Kuno; Chizuka Ide

2004-01-01

364

IMMUNODIAGNOSIS OF TUBERCULOUS MENINGITIS: DETECTION OF ANTIBODY REACTIVITY TO ANTIGENS OF MYCOBACTERIUM TUBERCULOSIS AND CYSTICERCUS CELLULOSAE IN CEREBROSPINAL FLUID TUBERCULOUS MENINGITIS PATIENTS BY ELISA  

Microsoft Academic Search

Enzyme-linked immunosorbent assay (ELISA) was standardized and evaluated for detection of antibody response in cerebrospinal fluid (CSF) to antigens of Mycobacterium tuberculosis and Cysticercus cellulosae. Sonicated extracts of heat killed M.tuberculosis H37Rv and C.cellulosae were prepared and used in ELISA to detect respective antibody response in CSFs for a definitive diagnosis as to tuberculous meningitis (TBM)\\/neurocysticercosis (NCC). ELISA was performed

Muralidhar K. Katti; Myna T. Acharya

2001-01-01

365

Saline extract of Taenia saginata metacestodes as an alternative antigen for the immunodiagnosis of neurocysticercosis in human cerebrospinal fluid.  

PubMed

The aim of the present research was to test the application of Taenia saginata metacestodes as an alternative antigen for use in enzyme-linked immunosorbent assay (ELISA) and Western Blotting (WB) tests compared with the use of metacestodes antigen of Taenia solium in cerebrospinal fluid (CSF) samples. The samples were obtained from 35 patients with definitive neurocysticercosis (NCC)-group 1-and 44 patients with other neurological disorders (control)-group 2. The sensitivity and specificity of ELISA, using antigen obtained from T. solium, applied to the patients of group 1 yielded results of 100%. When the tests were conducted using T. saginata metacestodes, results were 100% and 93.2%, respectively. The 47-52-, 64-68-, and 70-kDa antigens showed high frequencies in CSF samples from patients with NCC when WB was conducted with both antigens. The results indicate that T. saginata metacestodes can be used as an alternative antigen for the diagnosis of human NCC in CSF samples. PMID:19247689

Oliveira, Heliana B; Machado, Gleyce A; Gonçalves-Pires, Maria do Rosário F; Moura, Leandro P; Costa-Cruz, Julia M

2009-07-01

366

Neurocysticercosis: detection of Taenia solium DNA in human cerebrospinal fluid using a semi-nested PCR based on HDP2.  

PubMed

Human neurocysticercosis (NC) is caused by Taenia solium larvae lodged in the central nervous system. This disease is usually diagnosed by radiology but the results are not always clear-cut and so immunological assays are often also used. A semi-nested PCR, based on the non-coding HDP2 sequence of T. saginata, has now been developed for detecting DNA from T. solium cysticerci and confirming NC. This PCR, which amplifies a 171-bp T. solium product, allowed the specific detection of just 174 attograms of T. solium DNA. The efficacy of the PCR was tested using cerebrospinal fluid (CSF) from neurological patients, including 46 confirmed Mexican cases of NC and 32 patients from non-endemic Spain. Eighteen of the confirmed cases [including 10 (71%) of the 14 with vesicular extraparenchymal cysticerci and four (17%) of the 24 with damaged cysticerci] and two (33%) of the six patients with 'uncertain' diagnosis (in whom a diagnosis of NC could not be established by radiological and immunological studies) were found PCR-positive. The 36 patients known to have neurological problems other than NC were found PCR-negative. The HDP2 PCR offers a new tool in the diagnosis of NC and in exploring the pathogenesis of this serious disease. PMID:18510812

Hernández, M; Gonzalez, L M; Fleury, A; Saenz, B; Parkhouse, R M E; Harrison, L J S; Garate, T; Sciutto, E

2008-06-01

367

Cerebrospinal fluid and plasma C-reactive protein and aggression in personality-disordered subjects: a pilot study.  

PubMed

C-reactive protein (CRP), in the plasma, serves as a marker of systemic inflammation and has been shown to correlate with history of actual aggressive behavior, and as a personality trait of aggressive tendency, in human subjects. This pilot study was conducted to determine if plasma CRP levels are correlated with cerebrospinal fluid levels (CSF CRP) and if CSF CRP also correlates with aggression. If so, this would suggest a role for central inflammatory processes in human aggression. Both plasma and basal lumbar CSF samples were obtained from 17 subjects with DSM-5 personality disorder and assayed for CRP. Plasma and CSF CRP levels were correlated (r = 0.65, p = 0.005) and each correlated with aggression (Plasma: r = 0.53, p = 0.029; CSF: r = 0.84, p < 0.001). When considered simultaneously, CSF CRP, but not plasma CRP, uniquely correlated with aggression. No relationship was seen with other measures of psychopathology. These data suggest a positive relationship between central nervous system CRP and aggression in humans. PMID:25056708

Coccaro, Emil F; Lee, Royce; Coussons-Read, Mary

2015-02-01

368

Quantification of microRNA-210 in the cerebrospinal fluid and serum: Implications for Alzheimer’s disease  

PubMed Central

The aim of the present study was to investigate the potential clinical application of the genetic marker microRNA (miRNA)-210 in the cerebrospinal fluid (CSF) and serum of patients with Alzheimer’s disease (AD). The enrolled patients were divided into the mild cognitive impairment (MCI) and AD groups. Healthy individuals were used as the controls. The mRNA and protein expression of vascular endothelial growth factor (VEGF) in the CSF and serum samples was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. The expression of miRNA-210 in the CSF and serum was detected by RT-qPCR. The results revealed that the mRNA and protein expression levels of VEGF in the CSF and serum were decreased in the MCI and AD groups compared with those in the control group. The greater the severity of the dementia, the lower the mRNA and protein expression of VEGF. Similar to the trend observed for VEGF, the miRNA-210 expression in the CSF and serum decreased as the severity of the AD increased. miRNA-210 is thus not only indicative of AD pathogenesis, but may also provide novel insights into the prevention and treatment of the disease. PMID:25667669

ZHU, YAN; LI, CHENGSHAN; SUN, AICHEN; WANG, YUANYE; ZHOU, SHENGNIAN

2015-01-01

369

Changes in trace elements of cerebrospinal fluid after subarachnoid hemorrhage, and effects of trace elements on vasospasm  

NASA Astrophysics Data System (ADS)

Various causal factors have been proposed for cerebral vasospasm after subarachnoid hemorrhage (SAH), such as serotonin, acetylcholine, angiotensin, thrombin and thromboxane A2. However, none of them explain the whole pathomechanism of vasospasm. To evaluate the role of trace elements on vasospasm, we have examined these sequential changes in the cerebrospinal fluid (CSF) after SAH by PIXE, and have investigated the relation between trace elements and vasospasm. We obtained the CSF samples from cisternal drainage in patients with SAH who underwent radical surgery within 48 h from the onset. The drainage was placed into basal cisterns at the end of the operation. Three sampling times (3-5, 7-9 and 12-14 days from the onset) has been scheduled because vasospasm is likely to occur from day 4 to day 14 after the onset. In this study, we focused on the levels of Mg, Ca, Mn, Al, Zn, P, Pb, Sr, Br, Co, Cu, Si, Ti, Mn,Co, Cu, Zn, Br, Sr, Mo and Pb, and we found a significantly lower level of Mg in the CSF of patients with vasospasm on days 7-9 after the onset. These results suggest that Mg in the CSF may ameliorate vasoconstriction due to Ca in the pathomechanism of vasospasm.

Sato, N.; Kuroda, K.; Suzuki, M.; Ogawa, A.; Sera, K.

1999-04-01

370

An alternative derivatization method for the analysis of amino acids in cerebrospinal fluid by gas chromatography-mass spectrometry.  

PubMed

The determination of the concentrations of l-amino acids in cerebrospinal fluid (CSF) has been used to gain biochemical insight into central nervous system disorders. This paper describes a microwave-assisted derivatization (MAD) method using N,O-bis-(trimethylsilyl)trifluoroacetamide (BSTFA) as a derivatizing agent for determining the concentrations of l-amino acids in human CSF by gas chromatography with mass spectrometry (GC/MS). The experimental design used to optimize the conditions showed that the optimal derivatization time was 3min with a microwave power of 210W. The method showed good performance for the validation parameters. The sensitivity was very good, with limits of detection (LODs) ranging from 0.01?molL(-1) to 4.24?molL(-1) and limits of quantification (LOQs) ranging from 0.02 to 7.07?molL(-1). The precision, measured using the relative standard deviation (RSD), ranged from 4.12 to 15.59% for intra-day analyses and from 6.36 to 18.71% for inter-day analyses. The coefficients of determination (R(2)) were above 0.990 for all amino acids. The optimized and validated method was applied to the determination of amino acid concentrations in human CSF. PMID:23770739

de Paiva, Maria José Nunes; Menezes, Helvécio Costa; Christo, Paulo Pereira; Resende, Rodrigo Ribeiro; Cardeal, Zenilda de Lourdes

2013-07-15

371

Practical detection of a definitive biomarker panel for Alzheimer’s disease; comparisons between matched plasma and cerebrospinal fluid  

PubMed Central

Previous mass spectrometry analysis of cerebrospinal fluid (CSF) has allowed the identification of a panel of molecular markers that are associated with Alzheimer’s disease (AD). The panel comprises Amyloid beta, Apolipoprotein E, Fibrinogen alpha chain precursor, Keratin type I cytoskeletal 9, Serum albumin precursor, SPARC-like 1 protein and Tetranectin. Here we report the development and implementation of immunoassays to measure the abundance and diagnostic capacity of these putative biomarkers in matched lumbar CSF and blood plasma samples taken in life from individuals confirmed at post-mortem as suffering from AD (n = 10) and from screened ‘cognitively healthy’ subjects (n = 18). The inflammatory components of Alzheimer’s disease were also investigated. Employment of supervised learning techniques permitted examination of the interrelated expression patterns of the putative biomarkers and identified inflammatory components, resulting in biomarker panels with a diagnostic accuracy of 87.5% and 86.7% for the plasma and CSF datasets respectively. This is extremely important as it offers an ideal high-throughput and relatively inexpensive population screening approach. It appears possible to determine the presence or absence of AD based on our biomarker panel and it seems likely that a cheap and rapid blood test for AD is feasible. PMID:24959311

Richens, Joanna L; Vere, Kelly-Ann; Light, Roger A; Soria, Daniele; Garibaldi, Jonathan; Smith, A David; Warden, Donald; Wilcock, Gordon; Bajaj, Nin; Morgan, Kevin; O’Shea, Paul

2014-01-01

372

BK virus regulatory region rearrangements in brain and cerebrospinal fluid from a leukemia patient with tubulointerstitial nephritis and meningoencephalitis.  

PubMed

BK virus (BKV) was recovered by polymerase chain reaction (PCR) from brain, kidney, lung, urine, and cerebrospinal fluid (CSF) of a fatal case of BKV tubulointerstitial nephritis with dissemination to lung and brain. Viral regulatory regions in PCR-amplified urine and the lung samples were identical to the archetypal structure, WWT. In the brain and CSF, a rearranged sequence predominated, however. A 94-bp deletion preceded a 71-bp tandem duplication because the same 94-bp segment was deleted from both copies. PCR-amplified regulatory region products were cloned and sequenced to define further the extent of the rearranged structures. Two kidney clones were archetypal, whereas two others were rearranged differently from the brain and from each other. In contrast to the brain clones, the kidney rearrangements seemed to involve deletion after duplication. Three of four brain clones sequenced were identical to the rearrangement found to dominate in the PCR product. A fourth clone showed two short deletions without any duplication. The four CSF clones all showed rearrangements identical to that which was amplified by PCR from CSF and brain. This represents the first molecular analysis of a BKV strain obtained from a central nervous system infection, and it reveals regulatory region rearrangements reminiscent of those described in JC virus from brains with progressive multifocal leukoencephalopathy. We suggest that the presence in the CSF of BKV with a dominant rearranged regulatory region may be useful in the diagnosis of BKV meningoencephalitis secondary to BKV nephritis. PMID:11979356

Stoner, Gerald L; Alappan, Raj; Jobes, David V; Ryschkewitsch, Caroline F; Landry, Marie L

2002-05-01

373

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

PubMed

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 and parkinsonian squirrel monkeys in order to assess their reliability as indicators of nigrostriatal injury. In particular, we tested the hypothesis that these measurements may become more accurate by inhibiting catecholamine-O-methyltransferase (COMT) activity and therefore blocking the conversion of DOPAC to homovanillic acid. Oral administration of the COMT inhibitor tolcapone (2 doses of 15 mg/kg each with a 4-h interval) significantly reduced enzyme activity in the monkey brain. Tolcapone treatment enhanced CSF DOPAC concentrations in unlesioned animals (by approximately four times) as well as monkeys rendered parkinsonian after severe nigrostriatal dopaminergic injury caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Importantly, however, COMT inhibition greatly magnified the differences in CSF DOPAC levels between control and parkinsonian monkeys, since MPTP-induced DOPAC depletion was 35% in the absence vs >60% in the presence of tolcapone. Thus, tolcapone administration enhances the detection of DOPAC in the CSF and, by doing so, improves the reliability of CSF DOPAC as a marker of nigrostriatal degeneration. PMID:12957500

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

2003-09-01

374

Associations between the angiotensin-converting enzyme insertion/deletion polymorphism and monoamine metabolite concentrations in cerebrospinal fluid.  

PubMed

Angiotensin II has been suggested to influence central dopamine and serotonin turnover. Since the angiotensin-converting enzyme (ACE) plays a key role in angiotensin regulation by converting inactive angiotensin I to active angiotensin II, we hypothesised that the functional insertion/deletion (I/D) polymorphism in the ACE gene, which has previously been suggested to be associated with, depression and panic disorder, may influence monoamine activity. A well-established technique for assessing brain monoamine turnover in humans is to measure concentrations of monoamine metabolites in the cerebrospinal fluid (CSF). We thus investigated possible associations between the ACE I/D polymorphism and CSF monoamine metabolite concentrations in a population of healthy male subjects. After having found such an association between the ACE I/D polymorphism and CSF levels of the dopamine metabolite homovanillic acid and the serotonin metabolite 5-hydroxyindoleacetic acid in this sample, I carriers displaying lower levels, we tried to replicate this observation in a population of violent male offenders from which also both CSF and DNA were available. Also in this sample, the same associations were found. Our results suggest that the ACE I/D polymorphism may play a role in the modulation of serotonergic and dopaminergic turnover in men. PMID:20483169

Annerbrink, Kristina; Jönsson, Erik G; Olsson, Marie; Nilsson, Staffan; Sedvall, Göran C; Anckarsäter, Henrik; Eriksson, Elias

2010-09-30

375

Analysing the effect of early acetazolamide administration on patients with a high risk of permanent cerebrospinal fluid leakage.  

PubMed

In this study, we examined the role of early acetazolamide administration in reducing the risk of cerebrospinal fluid (CSF) leakage in patients with a high risk of permanent CSF leakage. In a randomised clinical trial, 57 patients with a high risk of permanent CSF leakage (rhinorrhea, otorrhea, pneumatocele or imaging-based evidence of severe skull-base fracture) were analysed. In the experimental group, acetazolamide, at 25 mg/kg/day, was started in the first 48 hours after admission. In the control group, acetazolamide was administered after the first 48 hours at the same dose administered to the patients in the experimental group. The following factors were compared between the two groups: duration of CSF leakage, duration of hospital stay, incidence of meningitis, need for surgical intervention and need for lumbar puncture (LP) and lumbar drainage (LD). All of the patients in the experimental group stopped having CSF leakage less than 14 days after the first day of admission, but 6 out of 21 patients (22%) in the control group continued having CSF leakage after 14 days of admission, which was a significant difference (P=0.01). This study showed that early acetazolamide administration can prevent CSF leakage in patients with a high risk of permanent CSF leak. PMID:23945891

Abrishamkar, Saeid; Khalighinejad, Nima; Moein, Payam

2013-01-01

376

Polymorphisms in genes implicated in dopamine, serotonin and noradrenalin metabolism suggest association with cerebrospinal fluid monoamine metabolite concentrations in psychosis  

PubMed Central

Background Homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) are the major monoamine metabolites in the central nervous system (CNS). Their cerebrospinal fluid (CSF) concentrations, reflecting the monoamine turnover rates in CNS, are partially under genetic influence and have been associated with schizophrenia. We have hypothesized that CSF monoamine metabolite concentrations represent intermediate steps between single nucleotide polymorphisms (SNPs) in genes implicated in monoaminergic pathways and psychosis. Methods We have searched for association between 119 SNPs in genes implicated in monoaminergic pathways [tryptophan hydroxylase 1 (TPH1), TPH2, tyrosine hydroxylase (TH), DOPA decarboxylase (DDC), dopamine beta-hydroxylase (DBH), catechol-O-methyltransferase (COMT), monoamine oxidase A (MAOA) and MAOB] and monoamine metabolite concentrations in CSF in 74 patients with psychotic disorder. Results There were 42 nominally significant associations between SNPs and CSF monoamine metabolite concentrations, which exceeded the expected number (20) of nominal associations given the total number of tests performed. The strongest association (p =?0.0004) was found between MAOB rs5905512, a SNP previously reported to be associated with schizophrenia in men, and MHPG concentrations in men with psychotic disorder. Further analyses in 111 healthy individuals revealed that 41 of the 42 nominal associations were restricted to patients with psychosis and were absent in healthy controls. Conclusions The present study suggests that altered monoamine turnover rates in CNS reflect intermediate steps in the associations between SNPs and psychosis. PMID:25073638

2014-01-01

377

HPLC analysis of para-aminosalicylic acid and its metabolite in plasma, cerebrospinal fluid and brain tissues  

PubMed Central

Para-aminosalicylic acid (PAS), an approved drug for treatment of tuberculosis, is a promising therapeutic agent for treatment of manganese (Mn)-induced parkinsonian syndromes. Lack of a quantifying method, however, has hindered the clinical evaluation of its efficacy and thereupon new drug development. This study was aimed at developing a simple and effective method to quantify PAS and its major metabolite, N-acetyl-para-aminosalicylic acid (AcPAS), in plasma, cerebrospinal fluid (CSF) and tissues. Biological samples underwent one-step protein precipitation. The supernatant was fractionated on a reversed-phase C18 column with a gradient mobile system, followed by on-line fluorescence detection. The lower limits of quantification for both PAS and AcPAS were 50 ng/ml of plasma and 17 ng/g of tissues. The intra-day and inter-day precision values did not exceed 5% and 8%, respectively, in all three matrices. The method was used to quantify PAS and AcPAS in rat plasma and brain following a single iv injection of PAS. Data showed a greater amount of PAS than AcPAS in plasma, while a greater amount of AcPAS than PAS was found in brain tissues. The method has been proven to be sensitive, reproducible, and practically useful for laboratory and clinical investigations of PAS in treatment of Mn Parkinsonism. PMID:21159459

Hong, Lan; Jiang, Wendy; Zheng, Wei; Zeng, Su

2011-01-01

378

Endoscopic endonasal skull base surgery: advantages, limitations, and our techniques to overcome cerebrospinal fluid leakage: technical note.  

PubMed

In recent years, resections of midline skull base tumors have been conducted using endoscopic endonasal skull base (EESB) approaches. Nevertheless, many surgeons reported that cerebrospinal fluid (CSF) leakage is still a major complication of these approaches. Here, we report the results of our 42 EESB surgeries and discuss the advantages and limits of this approach for resecting various types of tumors, and also report our technique to overcome CSF leakage. All 42 cases involved midline skull base tumors resected using the EESB technique. Dural incisions were closed using nasoseptal flaps and fascia patch inlay sutures. Total removal of the tumor was accomplished in seven pituitary adenomas (33.3%), five craniopharyngiomas (62.5%), five tuberculum sellae meningiomas (83.3%), three clival chordomas (100%), and one suprasellar ependymoma. Residual regions included the cavernous sinus, the outside of the intracranial part of the internal carotid artery, the lower lateral part of the posterior clivus, and the posterior pituitary stalk. Overall incidence of CSF leakage was 7.1%. Even though the versatility of the approach is limited, EESB surgery has many advantages compared to the transcranial approach for managing mid-line skull base lesions. To avoid CSF leakage, surgeons should have skills and techniques for complete closure, including use of the nasoseptal flap and fascia patch inlay techniques. PMID:25446379

Ishii, Yudo; Tahara, Shigeyuki; Teramoto, Akira; Morita, Akio

2014-12-15

379

Sustained Elevation of Kynurenic Acid in the Cerebrospinal Fluid of Patients with Herpes Simplex Virus Type 1 Encephalitis  

PubMed Central

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

Atlas, Ann; Franzen-Röhl, Elisabeth; Söderlund, Johan; Jönsson, Erik G; Samuelsson, Martin; Schwieler, Lilly; Sköldenberg, Birgit; Engberg, Göran

2013-01-01

380

Chemotherapy-induced cerebrospinal fluid malabsorption in a shunted child: case report and review of the literature  

PubMed Central

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

O'Halloran, Philip J; Kaliaperumal, Chandrasekaran; Caird, John

2013-01-01

381

The Causative Pathogen Determines the Inflammatory Profile in Cerebrospinal Fluid and Outcome in Patients with Bacterial Meningitis  

PubMed Central

Background. The brain's inflammatory response to the infecting pathogen determines the outcome of bacterial meningitis (BM), for example, the associated mortality and the extent of brain injury. The inflammatory cascade is initiated by the presence of bacteria in the cerebrospinal fluid (CSF) activating resident immune cells and leading to the influx of blood derived leukocytes. To elucidate the pathomechanisms behind the observed difference in outcome between different pathogens, we compared the inflammatory profile in the CSF of patients with BM caused by Streptococcus pneumonia (n = 14), Neisseria meningitidis (n = 22), and Haemophilus influenza (n = 9). Methods. CSF inflammatory parameters, including cytokines and chemokines, MMP-9, and nitric oxide synthase activity, were assessed in a cohort of patients with BM from Burkina Faso. Results. Pneumococcal meningitis was associated with significantly higher CSF concentrations of IFN-?, MCP-1, and the matrix-metalloproteinase (MMP-) 9. In patients with a fatal outcome, levels of TNF-?, IL-1?, IL-1RA, IL-6, and TGF-? were significantly higher. Conclusion. The signature of pro- and anti-inflammatory mediators and the intensity of inflammatory processes in CSF are determined by the bacterial pathogen causing bacterial meningitis with pneumococcal meningitis being associated with a higher case fatality rate than meningitis caused by N. meningitidis or H. influenzae. PMID:23864766

Grandgirard, Denis; Gäumann, Rahel; Coulibaly, Boubacar; Dangy, Jean-Pierre; Sie, Ali; Junghanss, Thomas; Schudel, Hans; Pluschke, Gerd; Leib, Stephen L.

2013-01-01

382

Leakage of cerebrospinal fluid and secondary intracranial infection induced by Cloward technique of cervical discectomy and fusion: presentation and treatment.  

PubMed

Cloward technique of cervical discectomy and fusion is a long and complex surgical procedure and instrumentation, by which complicated infection is rare in an era of routine prophylactic antimicrobial agent, especially in procedures by anterior approach. A study in the journal of Spine suggested that the incidence of unintentional laceration of the dura mater during spinal surgery might be as high as 14%.1 A majority of them are repaired intraoperatively and/or present as a spontaneous process of healing. Therefore, leakage of cerebrospinal fluid (CSF) and secondary intracranial infection induced by incidental durotomy are rare. Levi et al.2 reviewed spinal instrumentation procedures in 452 cases at a single institution, finding that 17 patients got infections in the operative areas. Infection occurred after posterior spinal instrumentation procedures (7.2%) and no infection was found after anterior instrumentation procedures regardless of the vertebral levels. Likewise, Aydinli et al.3 reported that 8 patients were complicated by acute infection out of 174 patients undergoing instrumented spinal surgery, including no anterior procedures. To our knowledge, we are the first to report a complete clinical course concerning CSF leakage and secondary intracranial infection induced by Cloward technique of cervical discectomy and fusion. PMID:18822198

Guo, Hong-bin; Yang, Shu-xu; Wang, Yi-rong

2008-10-01

383

A case of spontaneous cerebrospinal fluid rhinorrhea: Accurate detection of the leak point by magnetic resonance cisternography  

PubMed Central

Background: Spontaneous cerebrospinal fluid (CSF) rhinorrhea is a rare entity. The accurate preoperative localization of the leak point is essential for planning surgical treatment, but is sometimes difficult. To localize the leak point, magnetic resonance cisternography (MRC) is the method of choice, but its effectiveness remains unclear. Case Description: A 34-year-old mildly obese female experienced spontaneous CSF rhinorrhea after an attack of bronchial asthma. High-resolution computed tomography (CT) failed to reveal the leak point, while MRC demonstrated an arachnoid herniation at the olfactory cleft. The patient underwent endoscopic endonasal repair of the CSF leak with success. There has been no recurrence of CSF rhinorrhea for 14 months after surgery followed by the administration of acetazolamide. Conclusion: We report a rare case of spontaneous CSF rhinorrhea associated with benign intracranial hypertension, in which the leak point was successfully detected by MRC. The CSF leak was completely repaired by minimally invasive endoscopic endonasal surgery. MRC may be a reliable method for detecting CSF leak points. PMID:24872916

Matsubara, Teppei; Akutsu, Hiroyoshi; Tanaka, Shuho; Yamamoto, Tetsuya; Ishikawa, Eiichi; Matsumura, Akira

2014-01-01

384

Cerebrospinal fluid concentrations of functionally important amino acids and metabolic compounds in patients with mild cognitive impairment and Alzheimer's disease.  

PubMed

Cerebrospinal fluid (CSF) biomarkers play an important role in the differential diagnosis of neurodegenerative diseases such as Alzheimer's disease (AD) and its postulated precursor stage mild cognitive impairment (MCI). While CSF tau protein, phospho-tau protein and beta-amyloid have become part of the diagnostic process in clinical routine, the importance of several other biomarkers remains quite unclear. Among these, amino acids and metabolic compounds have been studied in clinical conditions mostly other than AD and, to our knowledge, never in MCI. In patients with AD (n = 14) and MCI (n = 13) we now determined CSF levels of 36 different amino acids and metabolic compounds by high-performance liquid chromatography. We found that 8 out of 36 amino acids (urea, threonine, glutamate, citrulline, alpha-aminobutyric acid, ornithine, ammonia and arginine) were significantly elevated in the CSF of patients with AD compared to those with MCI. As most of these amino acids and metabolic compounds are functionally important for brain-specific metabolic processes, neurotransmitter pathways or compensatory mechanisms, our findings might reflect these changes occurring within the brain of patients with MCI and those who developed manifest AD. PMID:20551690

Kaiser, Elmar; Schoenknecht, Peter; Kassner, Stefan; Hildebrandt, Wulf; Kinscherf, Ralf; Schroeder, Johannes

2010-01-01

385

Quantification of Plasmodium falciparum histidine-rich protein-2 in cerebrospinal spinal fluid from cerebral malaria patients.  

PubMed

A cerebrospinal fluid (CSF) biomarker for cerebral malaria (CM) has not been validated. We examined the detection, semiquantification, and clinical use of the Plasmodium falciparum histidine-rich protein-2 (PfHRP-2) as a parasite antigen biomarker for CM. The PfHRP-2 was detected in archival CSF samples from CM patients from Tanzania both by a newly developed sensitive and specific immuno-polymerase chain reaction (72 of 73) and by rapid diagnostic tests (62 of 73). The geometric mean PfHRP-2 CSF concentration was 8.76 ng/mL with no differences in those who survived (9.2 ng/mL), those who died (11.1 ng/mL), and those with neurologic sequelae (10.8 ng/mL). All aparasitemic endemic and nonendemic control samples had undetectable CSF PfHRP-2. In a separate group of 11 matched plasma and CSF cerebral malaria patient samples, the ratio of plasma to CSF PfHRP-2 was 175. The CSF PfHRP-2 reflects elevated plasma PfHRP-2 rather than elevated CM-specific CSF ratios, falling short of a validated biomarker. PMID:24980497

Mikita, Kei; Thakur, Kiran; Anstey, Nicholas M; Piera, Kim A; Pardo, Carlos A; Weinberg, J Brice; Mukemba, Jackson; Florence, Salvatore; Mwaikambo, Esther D; Granger, Donald L; Sullivan, David J

2014-09-01

386

External re-programmation by a new radionuclidic technique of electronic cerebrospinal fluid valve in case of hydrocephalus.  

PubMed

Hydrocephalus is defined as an abnormal enlargement of the ventricles of the brain due to an excessive accumulation of cerebrospinal fluid (CSF) because of a disturbance of its flow, absorption and/or secretion. The usual method of CSF diversion is a ventriculo-peritoneal shunt. Complications of implanted shunt systems include mechanical failure, shunt pathway obstruction, infection, foreign body (allergic) reaction to implants and CSF leakage along the implanted shunt pathway. These problems are solved with the use of programmable ventricular-peritoneal CSF valves. In this case, we describe a radionuclidic method for the control of successful reprogramming of the CSF valve. Furthermore, we analyze some technical data of such a valve-type are essential for the application of the above technique by nuclear medicine physicians. Scintigraphic evaluation of the electronic V-P drainage valve regulation is a noninvasive, not expensive, rapid and safe method with no complications for the patient and provides a reliable proof of the patency of the V-P shunt. PMID:19936336

Zissimopoulos, Athanassios; Birbilis, Theodossios; Cassimos, Dimitrios; Deftereos, Savas; Karathanos, Evangelos; Chatzimichael, Athanassios; Prassopoulos, Panos

2009-01-01

387

Lateral ventricular cerebrospinal fluid diffusivity as a potential neuroimaging marker of brain temperature in multiple sclerosis: a hypothesis and implications.  

PubMed

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

Hasan, Khader M; Lincoln, John A; Nelson, Flavia M; Wolinsky, Jerry S; Narayana, Ponnada A

2015-04-01

388

Kinetics of T-cell-based assays on cerebrospinal fluid and peripheral blood mononuclear cells in patients with tuberculous meningitis  

PubMed Central

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

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

389

Cerebrospinal fluid biochemical studies in patients with Parkinson's disease: toward a potential search for biomarkers for this disease  

PubMed Central

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

Jiménez-Jiménez, Félix J.; Alonso-Navarro, Hortensia; García-Martín, Elena; Agúndez, José A. G.

2014-01-01

390

Serotonin Metabolites in the Cerebrospinal Fluid in the Sudden Infant Death Syndrome: In Search of a Biomarker of Risk  

PubMed Central

Clinical biomarkers are urgently needed in the sudden infant death syndrome (SIDS) to identify living infants at risk because it because it occurs without occurs without clinical warning. Previously, we reported multiple serotonergic (5-HT) abnormalities in nuclei of the medulla oblongata that help mediate protective responses to homeostatic stressors. Here we test the hypothesis that 5-HT-related measures are abnormal in the cerebrospinal fluid (CSF) of SIDS infants compared to autopsy controls, as a first step towards their assessment as diagnostic biomarkers of medullary pathology. Levels of CSF 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), the degradative products of 5-HT and dopamine, respectively, were measured by high performance liquid chromatography in 57 SIDS and 29 non-SIDS autopsy cases. Tryptophan (Trp) and tyrosine (Tyr), the substrates of 5-HT and dopamine, respectively, were also measured. There were no significant differences in 5-HIAA, Trp, HVA, or Tyr levels between the SIDS and non-SIDS groups. These data preclude use of 5-HIAA, HVA, Trp or Tyr measurements as CSF biomarkers of 5-HT medullary pathology in infants at risk. They provide, however, important information about monoaminergic measurements in human CSF at autopsy and their developmental profile in infancy that is applicable to multiple pediatric disorders beyond SIDS. PMID:24423636

Rognum, Ingvar J.; Tran, Hoa; Haas, Elisabeth A.; Hyland, Keith; Paterson, David S.; Haynes, Robin L.; Broadbelt, Kevin G.; Harty, Brian J.; Mena, Othon; Krous, Henry F.; Kinney, Hannah C.

2015-01-01

391

Secretory phospholipase A2 activity in serum and cerebrospinal fluid of patients with relapsing-remitting multiple sclerosis.  

PubMed

An increasing body of evidence suggests that patients afflicted with multiple sclerosis (MS) show alterations in immunologic markers including increases in proinflammatory cytokine activity and inflammation. Secretory Phospholipase A2 (sPLA2) is one of the key molecules contributing to the production of inflammatory lipid mediators, mainly eicosanoids. They are considered proinflammatory enzymes and their inhibition has long been recognized as a desirable therapeutic target. The aim of this study was to measure the enzyme activity of sPLA2 both in serum and cerebrospinal fluid (CSF) of MS patients. Twenty MS patients accompanied with 20 age-sex matched controls were recruited. The results showed that the enzyme activity of serum sPLA2 was 0.007±0.021 (?mol/min/ml) in MS patients vs. 0.007±0.016 (?mol/min/ml) in patients with other neurological diseases as a control group (P=0.5). Our findings also indicated that there is no correlation (P=0.6) between CSF sPLA2 enzyme activity and MS disease when the results of two groups were compared (0.072±0.020 in cases vs. 0.071±0.01 in control group). The results suggest that the enzyme activity of sPLA2 is not altered during the disease course. PMID:23859159

Siroos, Bahaadin; Balood, Mohammad; Zahednasab, Hamid; Mesbah-Namin, Seyed Alireza; Pourgholy, Fatemeh; Harirchian, Mohammad Hossein

2013-09-15

392

Penetration of Drugs through the Blood-Cerebrospinal Fluid/Blood-Brain Barrier for Treatment of Central Nervous System Infections†  

PubMed Central

Summary: The entry of anti-infectives into the central nervous system (CNS) depends on the compartment studied, molecular size, electric charge, lipophilicity, plasma protein binding, affinity to active transport systems at the blood-brain/blood-cerebrospinal fluid (CSF) barrier, and host factors such as meningeal inflammation and CSF flow. Since concentrations in microdialysates and abscesses are not frequently available for humans, this review focuses on drug CSF concentrations. The ideal compound to treat CNS infections is of small molecular size, is moderately lipophilic, has a low level of plasma protein binding, has a volume of distribution of around 1 liter/kg, and is not a strong ligand of an efflux pump at the blood-brain or blood-CSF barrier. When several equally active compounds are available, a drug which comes close to these physicochemical and pharmacokinetic properties should be preferred. Several anti-infectives (e.g., isoniazid, pyrazinamide, linezolid, metronidazole, fluconazole, and some fluoroquinolones) reach a CSF-to-serum ratio of the areas under the curves close to 1.0 and, therefore, are extremely valuable for the treatment of CNS infections. In many cases, however, pharmacokinetics have to be balanced against in vitro activity. Direct injection of drugs, which do not readily penetrate into the CNS, into the ventricular or lumbar CSF is indicated when other effective therapeutic options are unavailable. PMID:20930076

Nau, Roland; Sörgel, Fritz; Eiffert, Helmut

2010-01-01

393

Tanycyte-Like Cells Form a Blood–Cerebrospinal Fluid Barrier in the Circumventricular Organs of the Mouse Brain  

PubMed Central

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

Langlet, Fanny; Mullier, Amandine; Bouret, Sebastien G.; Prevot, Vincent; Dehouck, Benedicte

2014-01-01

394

Tanycyte-like cells form a blood-cerebrospinal fluid barrier in the circumventricular organs of the mouse brain.  

PubMed

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

Langlet, Fanny; Mullier, Amandine; Bouret, Sebastien G; Prevot, Vincent; Dehouck, Benedicte

2013-10-15

395

Antibodies in Cerebrospinal Fluid of Some Alzheimer Disease Patients Recognize Cholinergic Neurons in the Rat Central Nervous System  

NASA Astrophysics Data System (ADS)

The etiology of Alzheimer disease is unclear. However, immunological aberrations have been suggested to be critical factors in the pathogenesis of this neurodegenerative disease. This study was carried out to investigate if cerebrospinal fluid (CSF) from Alzheimer disease patients contains antibodies that recognize specific neuronal populations in the rat central nervous system. The results indicate that in a subgroup of patients this is indeed the case. The antibodies reported in this study have the following properties: (i) they recognize neuronal populations and components in the medial septum and spinal motor neurons in rats perfused with a mixture that fixes small neurotransmitter molecules; (ii) adsorption of the patient CSF with staphylococcal protein A-Sepharose and using a polyclonal antiserum against human IgG3 indicates that the immunocytochemical reaction in these brain regions is mainly due to the subclass IgG3; and (iii) the CSF immunocytochemical reaction is blocked by preincubation of the sections with a rabbit anti-acetylcholine antiserum. These results provide evidence that antibodies in the CSF of some, but not all, Alzheimer disease patients recognize acetylcholine-like epitopes in cholinergic neurons in the rat central nervous system.

McRae-Degueurce, Amanda; Booj, Serney; Haglid, Kenneth; Rosengren, Lars; Karlsson, Jan Erik; Karlsson, Ingvar; Wallin, Anders; Svennerholm, Lars; Gottfries, Carl-Gerhard; Dahlstrom, Annica

1987-12-01

396

Triosephosphate isomerase- and glyceraldehyde-3-phosphate dehydrogenase-reactive autoantibodies in the cerebrospinal fluid of patients with multiple sclerosis.  

PubMed

Our previous results revealed that Igs in lesions and single chain variable fragment Abs (scFv-Abs) generated from clonal B cells in the cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS) bind to axons in MS brains. To study the axonal Ags involved in MS, we identified the glycolytic enzymes, triosephosphate isomerase (TPI) and GAPDH, using Igs from the CSF and scFv-Abs generated from clonal B cells in the CSF and in lesions from MS patients. Elevated levels of CSF-Abs to TPI were observed in patients with MS (46%), clinically isolated syndrome (CIS) suggestive of MS (40%), other inflammatory neurological diseases (OIND; 29%), and other noninflammatory neurological diseases (ONIND; 31%). Levels of GAPDH-reactive Abs were elevated in MS patients (60%), in patients with CIS (10%), OIND (14%), and ONIND (8%). The coexistence of both autoantibodies was detected in 10 MS patients (29%), and 1 CIS patient (3%), but not in patients with OIND/ONIND. Two scFv-Abs generated from the CSF and from lesions of a MS brain showed immunoreactivity to TPI and GAPDH, respectively. The findings suggest that TPI and GAPDH may be candidate Ags for an autoimmune response to neurons and axons in MS. PMID:17015754

Kolln, Johanna; Ren, Hui-Min; Da, Reng-Rong; Zhang, Yiping; Spillner, Edzard; Olek, Michael; Hermanowicz, Neal; Hilgenberg, Lutz G; Smith, Martin A; van den Noort, Stanley; Qin, Yufen

2006-10-15

397

Effects of intrathecal anesthesia with different concentrations and doses on spinal cord, nerve roots and cerebrospinal fluid in dogs  

PubMed Central

Objective: To investigate the effects of intrathecal anesthesia with bupivacaine, levobupivacaine and ropivacaine hydrochloride at different doses on the spinal cord, nerve roots and cerebrospinal fluid (CSF) in dogs. Methods: Forty-two mongrel dogs were randomly divided into normal saline group (C; 2 ml), 0.5% (B1) and 0.75% (B2) bupivacaine hydrochloride groups (2 ml), 0.5% (L1) and 0.75% (L2) levobupivacaine hydrochloride group (2 ml), 0.5% (R1) and 0.75% (R2) ropivacaine hydrochloride group (2 ml), and drugs were intrathecally injected. Results: The contents of Ca2+ and MDA and SOD activity of the spinal cord were comparable among groups (P > 0.05). In Groups B1, L1 and R1, the neuronal cytoplasm of spinal tissues was basically normal, the majority of mitochondria and endoplasmic reticulum had complete structure, and the lamellar structure of modulated fibers was nearly normal. In Groups B2, L2 and R2, a small amount of mitochondrial vacuolar degeneration was found in the neuronal cytoplasm of spinal cord, but their structures were basically normal; the neural tissues exhibited focal mild edema, and most of the lamellar structure of modulated fibers and Schwann cells were nearly normal except for loose structure in several fibers and cells. Conclusion: When compared with 0.75% anesthetics for local anesthesia, the early adverse effects on the ultrastructure of the spinal cord and nerve root reduce after focal anesthesia with 0.5% anesthetics.

Guo, Jianrong; Lv, Na; Su, Yongjun; Liu, Yang; Zhang, Jianping; Yang, Dawei

2014-01-01

398

BACE1 Inhibition Induces a Specific Cerebrospinal Fluid ?-Amyloid Pattern That Identifies Drug Effects in the Central Nervous System  

PubMed Central

BACE1 is a key enzyme for amyloid-? (A?) production, and an attractive therapeutic target in Alzheimer's disease (AD). Here we report that BACE1 inhibitors have distinct effects on neuronal A? metabolism, inducing a unique pattern of secreted A? peptides, analyzed in cell media from amyloid precursor protein (APP) transfected cells and in cerebrospinal fluid (CSF) from dogs by immunoprecipitation-mass spectrometry, using several different BACE1 inhibitors. Besides the expected reductions in A?1-40 and A?1-42, treatment also changed the relative levels of several other A? isoforms. In particular A?1-34 decreased, while A?5-40 increased, and these changes were more sensitive to BACE1 inhibition than the changes in A?1-40 and A?1-42. The effects on A?5-40 indicate the presence of a BACE1 independent pathway of APP degradation. The described CSF A? pattern may be used as a pharmacodynamic fingerprint to detect biochemical effects of BACE1-therapies in clinical trials, which might accelerate development of novel therapies. PMID:22328928

Mattsson, Niklas; Rajendran, Lawrence; Zetterberg, Henrik; Gustavsson, Mikael; Andreasson, Ulf; Olsson, Maria; Brinkmalm, Gunnar; Lundkvist, Johan; Jacobson, Laura H.; Perrot, Ludovic; Neumann, Ulf; Borghys, Herman; Mercken, Marc; Dhuyvetter, Deborah; Jeppsson, Fredrik; Blennow, Kaj; Portelius, Erik

2012-01-01

399

Lack of effect of chronic developmental lead treatment on biogenic amines and metabolites in monkey cerebrospinal fluid.  

PubMed

Concentrations of 3,4 dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), norepinephrine (NE), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) were assayed in the cerebrospinal fluid (CSF) of control and chronically lead-treated nursery-reared rhesus monkeys sampled periodically from infancy through adulthood. Blood lead levels peaked at 62 micrograms/dl at 1.5 months of age, averaged 45 micrograms/dl for the remainder of the first year postpartum, and were maintained at 14 micrograms/dl from 20-58 months of age. Cisternal CSF samples were collected monthly from 5-35 months of age and every 1-4 months from 36-58 months of age. Biogenic amine and metabolite concentrations were assayed by high-performance liquid chromatography with electrochemical detection. Overall concentrations of DOPAC, HVA, NE, MHPG, and 5-HIAA were not significantly different in the control and lead-treated groups nor were there any significant interactions between lead treatment and age for any measure. DOPAC, HVA, and 5-HIAA concentrations decreased gradually with age, whereas MHPG concentration decreased sharply between 35 and 40 months of age. NE concentration remained stable across development. PMID:8413076

Ferguson, S A; Kraemer, G W; Bowman, R E; Schmidt, D E; Ebert, M H

1993-01-01

400

Molecular forms of somatostatin-like immunoreactivity in the cerebrospinal fluid of patients with senile dementia of the Alzheimer type.  

PubMed

In the cerebrospinal fluid (CSF) of 53 patients with senile dementia of the Alzheimer type (SDAT) and 12 elderly controls, we measured somatostatin (SLI) and its molecular forms: high-molecular weight form (HMV-SST), somatostatin-14 (SST-14), somatostatin-25/28 (SST-28/25), and des-ala-somatostatin (des-ala-SST) using high pressure liquid chromatography (HPLC) and a radioimmunoassay. In SDAT, SLI was significantly decreased (p < 0.05) and correlated with dementia scores (r = -0.65, p < 0.05). HPLC separation showed a marked heterogeneity of SLI in the CSF with a preponderance of SST-14 and SST-25/28. The significant loss of SST-14 (p < 0.05) in SDAT was found to be correlated with dementia scores (r = 0.65). Moreover, qualitative and quantitative changes in the molecular pattern of SLI in SDAT indicated dysregulated synthesis and/or processing of somatostatin relating to the severity of dementia. The long-term administration of neuroleptics in severe cases of SDAT caused a significant increase of SLI (p < 0.05) and influenced the ratio of HMV-SST/SST-14 and SST25/28/SST-14. PMID:9146823

Strittmatter, M; Cramer, H; Reuner, C; Strubel, D; Hamann, G; Schimrigk, K

1997-06-01