Cerebrospinal fluid research最新文献

Background: Intracranial arachnoid cysts (AC) are membranous sacs filled with CSF-like fluid that are commonly found in the temporal fossa. The majority of ACs are congenital. Typical symptoms are headache, dizziness, and dyscognition. Little is known about genes that contribute to the formation of the cyst membranes.

Methods: In order to identify differences in gene expression between normal arachnoid membrane (AM) and cyst membrane, we have performed a high-resolution mRNA microarray analysis. In addition we have screened DNA from AC samples for chromosomal duplications or deletions using DNA microarray-based copy number variation analysis.

Results: The transcriptome consisting of 33096 gene probes showed a near-complete similarity in expression between AC and AM samples. Only nine genes differed in expression between the two tissues: ASGR1, DPEP2, SOX9, SHROOM3, A2BP1, ATP10D, TRIML1, NMU were down regulated, whereas BEND5 was up regulated in the AC samples. Three of the AC samples had unreported human DNA copy number variations, all DNA gains.

Conclusions: Extending results of previous anatomical studies, the present study has identified a small subset of differentially expressed genes and DNA alterations in arachnoid cysts compared to normal arachnoid membrane.

Background: We have previously seen that idiopathic normal pressure hydrocephalus (iNPH) patients having elevated intracranial pressure (ICP) pulse amplitude consistently respond to shunt surgery. In this study we explored how the cerebrospinal fluid pressure (CSFP) pulse amplitude determined during lumbar infusion testing, correlates with ICP pulse amplitude determined during over-night ICP monitoring and with response to shunt surgery. Our goal was to establish a more reliable screening procedure for selecting iNPH patients for shunt surgery using lumbar intrathecal infusion.

Methods: The study population consisted of all iNPH patients undergoing both diagnostic lumbar infusion testing and continuous over-night ICP monitoring during the period 2002-2007. The severity of iNPH was assessed using our NPH grading scale before surgery and 12 months after shunting. The CSFP pulse was characterized from the amplitude of single pressure waves.

Results: Totally 62 iNPH patients were included, 45 of them underwent shunt surgery, in whom 78% were shunt responders. Among the 45 shunted patients, resistance to CSF outflow (R(out)) was elevated (>or= 12 mmHg/ml/min) in 44. The ICP pulse amplitude recorded over-night was elevated (i.e. mean ICP wave amplitude >or= 4 mmHg) in 68% of patients; 92% of these were shunt responders. In those with elevated overnight ICP pulse amplitude, we found also elevated CSFP pulse amplitude recorded during lumbar infusion testing, both during the opening phase following lumbar puncture and during a standardized period of lumbar infusion (15 ml Ringer over 10 min). The clinical response to shunting after 1 year strongly associated with the over-night ICP pulse amplitude, and also with the pulsatile CSFP during the period of lumbar infusion. Elevated CSFP pulse amplitude during lumbar infusion thus predicted shunt response with sensitivity of 88 and specificity of 60 (positive and negative predictive values of 89 and 60, respectively).

Conclusions: In iNPH patients, shunt response can be anticipated in 9/10 patients with elevated overnight ICP pulse amplitude, while in only 1/10 with low ICP pulse amplitude. Additionally, the CSFP pulse amplitude during lumbar infusion testing was elevated in patients with elevated over-night ICP pulse amplitude. In particular, measurement of CSFP pulse amplitude during a standardized infusion of 15 ml Ringer over 10 min was useful in predicting response to shunt surgery and can be used as a screening procedure for selection of iNPH patients for shunting.

Background: We recently reported a lymphatic cerebrospinal fluid (CSF) absorption deficit in a kaolin model of communicating hydrocephalus in rats with ventricular expansion correlating negatively with the magnitude of the impediment to lymphatic function. However, it is possible that CSF drainage was not significantly altered if absorption at other sites compensated for the lymphatic defect. The purpose of this study was to investigate the impact of the lymphatic absorption deficit on global CSF absorption (CSF outflow resistance).

Methods: Kaolin was injected into the basal cisterns of Sprague Dawley rats. The development of hydrocephalus was assessed using magnetic resonance imaging (MRI). In one group of animals at about 3 weeks after injection, the movement of intraventricularly injected iodinated human serum albumin (125I-HSA) into the olfactory turbinates provided an estimate of CSF transport through the cribriform plate into nasal lymphatics (n = 18). Control animals received saline in place of kaolin (n = 10). In a second group at about 3.5 weeks after kaolin injection, intraventricular pressure was measured continuously during infusion of saline into the spinal subarachnoid space at various flow rates (n = 9). CSF outflow resistance was calculated as the slope of the steady-state pressure versus flow rate. Control animals for this group either received no injections (intact: n = 11) or received saline in place of kaolin (n = 8).

Results: Compared to saline injected controls, lateral ventricular volume in the kaolin group was significantly greater (0.087 +/- 0.013 ml, n = 27 versus 0.015 +/- 0.001 ml, n = 17) and lymphatic function was significantly less (2.14 +/- 0.72% injected/g, n = 18 versus 6.38 +/- 0.60% injected/g, n = 10). Additionally, the CSF outflow resistance was significantly greater in the kaolin group (0.46 +/- 0.04 cm H2O microL(-1) min, n = 9) than in saline injected (0.28 +/- 0.03 cm H2O microL(-1) min, n = 8) or intact animals (0.18 +/- 0.03 cm H2O microL(-1) min, n = 11). There was a significant positive correlation between CSF outflow resistance and ventricular volume.

Conclusions: The data suggest that the impediment to lymphatic CSF absorption in a kaolin-induced model of communicating hydrocephalus has a significant impact on global CSF absorption. A lymphatic CSF absorption deficit would appear to play some role (either direct or indirect) in the pathogenesis of ventriculomegaly.

Background: Cerebrospinal fluid (CSF) sodium levels have been reported to rise during episodic migraine. Since migraine frequently starts in early morning or late afternoon, we hypothesized that natural sodium chronobiology may predispose susceptible persons when extracellular CSF sodium increases. Since no mammalian brain sodium rhythms are known, we designed a study of healthy humans to test if cation rhythms exist in CSF.

Methods: Lumbar CSF was collected every ten minutes at 0.1 mL/min for 24 h from six healthy participants. CSF sodium and potassium concentrations were measured by ion chromatography, total protein by fluorescent spectrometry, and osmolarity by freezing point depression. We analyzed cation and protein distributions over the 24 h period and spectral and permutation tests to identify significant rhythms. We applied the False Discovery Rate method to adjust significance levels for multiple tests and Spearman correlations to compare sodium fluctuations with potassium, protein, and osmolarity.

Results: The distribution of sodium varied much more than potassium, and there were statistically significant rhythms at 12 and 1.65 h periods. Curve fitting to the average time course of the mean sodium of all six subjects revealed the lowest sodium levels at 03.20 h and highest at 08.00 h, a second nadir at 09.50 h and a second peak at 18.10 h. Sodium levels were not correlated with potassium or protein concentration, or with osmolarity.

Conclusion: These CSF rhythms are the first reports of sodium chronobiology in the human nervous system. The results are consistent with our hypothesis that rising levels of extracellular sodium may contribute to the timing of migraine onset. The physiological importance of sodium in the nervous system suggests that these rhythms may have additional repercussions on ultradian functions.

Background: Human equilibrative nucleoside transporters (hENTs) 1-3 and human concentrative nucleoside transporters (hCNTs) 1-3 in the human choroid plexus (hCP) play a role in the homeostasis of adenosine and other naturally occurring nucleosides in the brain; in addition, hENT1, hENT2 and hCNT3 mediate membrane transport of nucleoside reverse transcriptase inhibitors that could be used to treat HIV infection, 3'-azido-3'-deoxythymidine, 2'3'-dideoxycytidine and 2'3'-dideoxyinosine. This study aimed to explore the expression levels and functional activities of hENTs 1-3 and hCNTs 1-3 in human choroid plexus.

Methods: Freshly-isolated pieces of lateral ventricle hCP, removed for various clinical reasons during neurosurgery, were obtained under Local Ethics Committee approval. Quantification of mRNAs that encoded hENTs and hCNTs was performed by the hydrolysis probes-based reverse transcription real time-polymerase chain reaction (RT-qPCR); for each gene of interest and for 18 S ribosomal RNA, which was an endogenous control, the efficiency of PCR reaction (E) and the quantification cycle (Cq) were calculated. The uptake of [(3)H]inosine by the choroid plexus pieces was investigated to explore the functional activity of hENTs and hCNTs in the hCP.

Results: RT-qPCR revealed that the mRNA encoding the intracellularly located transporter hENT3 was the most abundant, with E(-Cq )value being only about 40 fold less that the E(-Cq )value for 18 S ribosomal RNA; mRNAs encoding hENT1, hENT2 and hCNT3 were much less abundant than mRNA for the hENT3, while mRNAs encoding hCNT1 and hCNT2 were of very low abundance and not detectable. Uptake of [(3)H]inosine by the CP samples was linear and consisted of an Na(+)-dependent component, which was probably mediated by hCNT3, and Na(+)-independent component, mediated by hENTs. The latter component was not sensitive to inhibition by S-(4-nitrobenzyl)-6-thioinosine (NBMPR), when used at a concentration of 0.5 muM, a finding that excluded the involvement of hENT1, but it was very substantially inhibited by 10 muM NBMPR, a finding that suggested the involvement of hENT2 in uptake.

Conclusion: Transcripts for hENT1-3 and hCNT3 were detected in human CP; mRNA for hENT3, an intracellularly located nucleoside transporter, was the most abundant. Human CP took up radiolabelled inosine by both concentrative and equilibrative processes. Concentrative uptake was probably mediated by hCNT3; the equilibrative uptake was mediated only by hENT2. The hENT1 transport activity was absent, which could suggest either that this protein was absent in the CP cells or that it was confined to the basolateral side of the CP epithelium.

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.

Background: The influence of coughing, on the biomechanical environment in the spinal subarachnoid space (SAS) in the presence of a cerebrospinal fluid flow stenosis, is thought to be an important etiological factor in craniospinal disorders, including syringomyelia (SM), Chiari I malformation, and hydrocephalus. The aim of this study was to investigate SAS and syrinx pressures during simulated coughing using in vitro models and to provide information for the understanding of the craniospinal fluid system dynamics to help develop better computational models.

Methods: Four in vitro models were constructed to be simplified representations of: 1) non-communicating SM with spinal SAS stenosis; 2) non-communicating SM due to spinal SAS stenosis with a distensible spinal column; 3) non-communicating SM post surgical removal of a spinal SAS stenosis; and 4) a spinal SAS stenosis due to spinal trauma. All of the models had a flexible spinal cord. To simulate coughing conditions, an abrupt CSF pressure pulse (~ 5 ms) was imposed at the caudal end of the spinal SAS by a computer-controlled pump. Pressure measurements were obtained at 4 cm intervals along the spinal SAS and syrinx using catheter tip transducers.

Results: Pressure measurements during a simulated cough, showed that removal of the stenosis was a key factor in reducing pressure gradients in the spinal SAS. The presence of a stenosis resulted in a caudocranial pressure drop in the SAS, whereas pressure within the syrinx cavity varied little caudocranially. A stenosis in the SAS caused the syrinx to balloon outward at the rostral end and be compressed at the caudal end. A >90% SAS stenosis did not result in a significant Venturi effect. Increasing compliance of the spinal column reduced forces acting on the spinal cord. The presence of a syrinx in the cord when there was a stenosis in the SAS, reduced pressure forces in the SAS. Longitudinal pressure dissociation acted to suck fluid and tissue caudocranially in the SAS with a stenosis.

Conclusions: Pressures in the spinal SAS during a simulated cough in vitro had similar peak, transmural, and longitudinal pressures to in vivo measurements reported in the literature. The pressure wave velocities and pressure gradients during coughing (longitudinal pressure dissociation and transmural pressure) were impacted by alterations in geometry, compliance, and the presence of a syrinx and/or stenosis.

Background: Popular circulation theory of hydrocephalus assumes that the brain is impermeable to cerebrospinal fluid (CSF), and is therefore incapable of absorbing the CSF accumulating within the ventricles. However, the brain parenchyma is permeable to water due to the presence of specific ion channels as well as aquaporin channels. Thus, the movement of water into and out of the ventricles may be determined by the osmotic load of the CSF. If osmotic load determines the aqueous content of CSF in this manner, it is reasonable to hypothesize that hydrocephalus may be precipitated by pathologies and/or insults that produce sustained elevations of osmotic content within the ventricles.

Methods: We investigated this hypothesis by manipulating the osmotic content of CSF and assaying the development of hydrocephalus in the rat brain. This was achieved by continuously infusing artificial CSF (negative control; group I), fibroblast growth factor (FGF2) solution (positive control; group II) and hyperosmotic dextran solutions (10 KD and 40 KD as experimental solutions: groups III and IV) for 12 days at 0.5 muL/h. The osmolality of the fluid infused was 307, 664, 337 and 328 mOsm/L in Groups I, II, III and IV, respectively. Magnetic resonance imaging (MRI) was used to evaluate the ventricular volumes. Analysis of variance (ANOVA) with pairwise group comparisons was done to assess the differences in ventricular volumes among the four groups.

Results: Group I had no hydrocephalus. Group II, group III and group IV animals exhibited significant enlargement of the ventricles (hydrocephalus) compared to group I. There was no statistically significant difference in the size of the ventricles between groups II, III and IV. None of the animals with hydrocephalus had obstruction of the aqueduct or other parts of CSF pathways on MRI.

Conclusion: Infusing hyperosmolar solutions of dextran, or FGF into the ventricles chronically, resulted in ventricular enlargement. These solutions increase the osmotic load in the ventricles. Water influx (through the choroid plexus CSF secretion and/or through the brain) into the ventricles to normalize this osmotic gradient results in hydrocephalus. We need to revise the popular theory of how fluid accumulates in the ventricles at least in some forms of hydrocephalus.