Brain Cooling and Cleaning: A New Perspective in Cerebrospinal Fluid (CSF) Dynamics

Background: The aim of this study was to present the proteomic approach based on liquid phase isoelectric focusing fractionation coupled to nLC-MALDI-TOF/TOF-MS/MS analysis to characterize cerebrospinal fluid from control patients and those suffering from subarachnoid hemorrhage. The new perspective in characterization of this brain neuropathology are in constant demand to point a valuable panel of indicators which could improve the treatment outcome.Methods: The cerebrospinal fluid samples were applied to a commercial liquid phase isoelectric focusing apparatus and separated into 10 fractions by pI. Further, the untargeted mass spectrometry investigations were performed with data dependent acquisition mode for full-scan MS analysis with subsequently MS/MS fragmentation by using nLC-MALDI-TOF/TOF-MS/MS.Results: In total, the detection of 1664 and 2187 unique tryptic peptides provided biological evidence for 134 and 271 proteins in control and subarachnoid hemorrhage sample, respectively. The interpretation of liquid phase separation was performed by intersection analysis of two items between groups of ten fractions. The cumulative intersection exploration revealed the highest concentration of the detected components in the middle fractions of the focusing chamber, whereas the gradual dilution appeared on its extreme.Conclusions: The employed strategy ensured overall screening of investigated material presenting the proteins abundance in the current state of analysis. Few proteins such as proenkephalin A, peroxiredoxin-6, cathepsin B, thrombospondin-1, glial fibrillary acidic protein and α – spectrin were recognized as potential indicators, according to literature, pointing the possibility for its monitoring in further studies as panel of valuable biomarkers.

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Hydrocephalus and normal CSF dynamics

Oxford Textbook of Neurological Surgery ◽

10.1093/med/9780198746706.003.0092 ◽

2019 ◽

pp. 1057-1070

Author(s):

Alexander Gamble ◽

Harold Rekate

Keyword(s):

Cerebrospinal Fluid ◽

Intracranial Pressure ◽

Systemic Circulation ◽

Production Flow ◽

Csf Dynamics ◽

New Techniques ◽

Clinical Disorders ◽

Fluid Production

Hydrocephalus is a condition characterized by a dynamic imbalance between the formation (production) and absorption of spinal fluid resulting in an increase in the size of the ventricular spaces. New techniques used to study the chemistry and physics of cerebrospinal fluid production, flow and absorption have led to new insights into the pathophysiology of hydrocephalus and other abnormalities of cerebrospinal fluid (CSF) dynamics. The importance of research into the role of aquaporins, other channel types and absorption of CSF into the systemic circulation via the lymphatics and intraparenchymal veins opens alternative explanations for enigmatic disorders of CSF. A contemporary classification of hydrocephalus based on the point of restriction of CSF flow has been shown to explain all problems related to clinical disorders of CSF and intracranial pressure. The distinct differences between hydrocephalus which develops in babies with growing heads and those that become symptomatic later in life.

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Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep

Science ◽

10.1126/science.aax5440 ◽

2019 ◽

Vol 366 (6465) ◽

pp. 628-631 ◽

Cited By ~ 104

Author(s):

Nina E. Fultz ◽

Giorgio Bonmassar ◽

Kawin Setsompop ◽

Robert A. Stickgold ◽

Bruce R. Rosen ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Brain Function ◽

Slow Waves ◽

Neural Dynamics ◽

Rapid Eye Movement Sleep ◽

Csf Flow ◽

Csf Dynamics ◽

Macroscopic Scale ◽

Waste Products ◽

The Brain

Sleep is essential for both cognition and maintenance of healthy brain function. Slow waves in neural activity contribute to memory consolidation, whereas cerebrospinal fluid (CSF) clears metabolic waste products from the brain. Whether these two processes are related is not known. We used accelerated neuroimaging to measure physiological and neural dynamics in the human brain. We discovered a coherent pattern of oscillating electrophysiological, hemodynamic, and CSF dynamics that appears during non–rapid eye movement sleep. Neural slow waves are followed by hemodynamic oscillations, which in turn are coupled to CSF flow. These results demonstrate that the sleeping brain exhibits waves of CSF flow on a macroscopic scale, and these CSF dynamics are interlinked with neural and hemodynamic rhythms.

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The arrest of treated hydrocephalus in children

Journal of Neurosurgery ◽

10.3171/jns.1984.61.4.0752 ◽

1984 ◽

Vol 61 (4) ◽

pp. 752-756 ◽

Cited By ~ 17

Author(s):

Ian H. Johnston ◽

Robert Howman-Giles ◽

Ian R. Whittle

Keyword(s):

Cerebrospinal Fluid ◽

Clinical Findings ◽

Communicating Hydrocephalus ◽

Csf Dynamics ◽

Aqueduct Stenosis ◽

Content Type ◽

A Prospective Study ◽

Neonates And Infants ◽

Radionuclide Scanning ◽

Fine Print

✓ A prospective study was made of the incidence of arrest of treated non-neoplastic hydrocephalus in 30 neonates and infants over a 5-year period. Radionuclide assessment of shunt function and cerebrospinal fluid (CSF) dynamics was carried out at intervals over this period, using a method that allowed injection of the radionuclide into the ventricular system independent of the shunt apparatus. The radionuclide scanning results were correlated with computerized tomography and clinical findings. Of 24 patients still available for analysis at the end of 5 years, four patients showed restoration of CSF circulation independent of the shunt apparatus and, in three of these, the shunt has either been clipped or clipped and removed without any ill effects. Clinical details of these three patients are provided. Two initially had communicating hydrocephalus, and one had probable aqueduct stenosis.

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Anthropomorphic Model of Intrathecal Cerebrospinal Fluid Dynamics Within the Spinal Subarachnoid Space: Spinal Cord Nerve Roots Increase Steady-Streaming

Journal of Biomechanical Engineering ◽

10.1115/1.4040401 ◽

2018 ◽

Vol 140 (8) ◽

Cited By ~ 11

Author(s):

Mohammadreza Khani ◽

Lucas R. Sass ◽

Tao Xing ◽

M. Keith Sharp ◽

Olivier Balédent ◽

...

Keyword(s):

Fluid Dynamics ◽

Spinal Cord ◽

Cerebrospinal Fluid ◽

Cfd Model ◽

Csf Flow ◽

Nerve Roots ◽

Csf Dynamics ◽

Steady Streaming ◽

Spinal Subarachnoid Space ◽

The Impact

Cerebrospinal fluid (CSF) dynamics are thought to play a vital role in central nervous system (CNS) physiology. The objective of this study was to investigate the impact of spinal cord (SC) nerve roots (NR) on CSF dynamics. A subject-specific computational fluid dynamics (CFD) model of the complete spinal subarachnoid space (SSS) with and without anatomically realistic NR and nonuniform moving dura wall deformation was constructed. This CFD model allowed detailed investigation of the impact of NR on CSF velocities that is not possible in vivo using magnetic resonance imaging (MRI) or other noninvasive imaging methods. Results showed that NR altered CSF dynamics in terms of velocity field, steady-streaming, and vortical structures. Vortices occurred in the cervical spine around NR during CSF flow reversal. The magnitude of steady-streaming CSF flow increased with NR, in particular within the cervical spine. This increase was located axially upstream and downstream of NR due to the interface of adjacent vortices that formed around NR.

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Immediate Impact of Yogic Breathing on Pulsatile Cerebrospinal Fluid Dynamics

10.1101/2021.08.09.455068 ◽

2021 ◽

Author(s):

Selda Yildiz ◽

John Grinstead ◽

Andrea Hildebrand ◽

John Oshinski ◽

William D. Rooney ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Spontaneous Breathing ◽

Controlled Trial ◽

Critical Role ◽

Csf Dynamics ◽

Waste Products ◽

Yogic Breathing ◽

Abdominal Breathing ◽

The Impact ◽

The Brain

Cerebrospinal fluid (CSF), a clear fluid bathing the central nervous system (CNS), undergoes pulsatile movements, and plays a critical role for the removal of waste products from the brain including amyloid beta, a protein associated with Alzheimer's disease. Regulation of CSF dynamics is critical for maintaining CNS health, and increased pulsatile CSF dynamics may alter brain's waste clearance due to increased mixing and diffusion. As such, understanding the mechanisms driving CSF movement, and interventions that influence its resultant removal of wastes from the brain is of high scientific and clinical impact. Since pulsatile CSF dynamics is sensitive and synchronous to respiratory movements, we are interested in identifying potential integrative therapies such as yogic breathing to regulate and enhance CSF dynamics, which has not been reported before. Here, we investigated the pre-intervention baseline data from our ongoing randomized controlled trial, and examined whether yogic breathing immediately impacts pulsatile CSF dynamics compared to spontaneous breathing. We utilized our previously established non-invasive real-time phase contrast magnetic resonance imaging (RT-PCMRI) approach using a 3T MRI instrument, and computed and rigorously tested differences in CSF velocities (instantaneous, respiratory, cardiac 1st and 2nd harmonics) at the level of foramen magnum during spontaneous versus four yogic breathing patterns. In examinations of 18 healthy participants (eight females, ten males; mean age 34.9 ± 14 (SD) years; age range: 18-61 years), we discovered immediate increase in cranially-directed velocities of instantaneous-CSF 16% - 28% and respiratory-CSF 60% - 118% during yogic versus spontaneous breathing, with most statistically significant changes during deep abdominal breathing (28%, p=0.0008, and 118%, p=0.0001, respectively). Further, cardiac pulsation was the primary source of pulsatile CSF during all breathing conditions except during deep abdominal breathing, when there was a comparable contribution of respiratory and cardiac 1st harmonic power [0.59 ± 0.78], demonstrating respiration can be the primary regulator of CSF depending on individual differences in breath depth and location. Further work is needed to investigate the impact of sustained training yogic breathing on increased pulsatile CSF dynamics and brain waste clearance for CNS health.

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Diagnostic capabilities of lumbar puncture in patients who have suffered in the past closed brain trauma and neuroinfection

Kazan medical journal ◽

10.17816/kazmj59803 ◽

1982 ◽

Vol 63 (1) ◽

pp. 46-47

Author(s):

E. N. Leksin

Keyword(s):

Cerebrospinal Fluid ◽

Lumbar Puncture ◽

Brain Trauma ◽

Laboratory Research ◽

Sitting Position ◽

Csf Dynamics ◽

Jugular Veins ◽

Csf Pressure ◽

The Past ◽

Diagnostic Capabilities

Our task was to find out the possibility of wider use of lumbar puncture for diagnostic purposes and to unify the registration of the data obtained. To do this, we performed the Queckenstedt test in patients with sequelae of closed brain trauma who had no contraindications to lumbar puncture with the study of CSF dynamics (fundus congestion, Bruns syndrome, bulbar syndrome). The following six indicators were recorded: CSF pressure (LD) in the patient's lying position; LD in the sitting position of the patient; maximum LD with Kvekkenstedt's test (after 10 s of continuous compression of the jugular veins); minimum LD at Kvekkenstedt's test (10 s after the termination of compression of the jugular veins); LD after the release of a certain (usually 3-6 ppm) amount of cerebrospinal fluid required for laboratory research; the total amount of released liquor, usually collected in three test tubes - for clinical (protein, cytosis, sediment microscopy), biochemical (sugar, chlorides, calcium, etc.) and serological (Wasserman river, etc.) studies.

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Abstract WMP86: Evaluation of Cerebrospinal Fluid Dynamics and External Ventricular Drain Management in the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage trial (CLEAR III)

Stroke ◽

10.1161/str.47.suppl_1.wmp86 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Wendy Ziai ◽

Mariam Bhuiyan ◽

Nichol McBee ◽

Rachel Dlugash ◽

Kevin Sheth ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Intraventricular Hemorrhage ◽

Obstructive Hydrocephalus ◽

External Ventricular Drain ◽

Randomized Study ◽

Recombinant Tissue Plasminogen Activator ◽

Clot Lysis ◽

Csf Dynamics ◽

Double Blind ◽

Csf Drainage

Background: Acute obstructive hydrocephalus secondary to spontaneous intracerebral/intraventricular hemorrhage (ICH/IVH) requires early cerebrospinal fluid (CSF) drainage to reduce intracranial pressure (ICP). Extensive CSF drainage may reduce IVH clot burden. We characterize CSF dynamics, strategies and impact on end of treatment (EOT) IVH volume (72 hours post randomization [Rand]) in the CLEAR III trial. Methods: Prospective analysis of CSF output in all 500 patients enrolled in the CLEAR III trial, a multicenter, double-blind, randomized study comparing EVD + intraventricular recombinant tissue plasminogen activator (rtPA) vs. EVD + placebo for treatment of obstructive IVH and intracerebral hemorrhage (ICH) volume <30cc. CSF output was recorded every 4 hours until 7 days post Rand, and compared by clinical and radiological variables. Results: Daily median CSF output in the first week was 188cc (IQR: 125, 252). Maximum daily EVD drip settings were <10mmHg in 27.8%, =10 in 44.1% and >10 in 28.1%. Independent predictors of higher daily CSF output after adjustment for initial IVH volume (p=0.04) were lower drip setting (p<0.001), lower age (p<0.001), male sex (p=0.03), dual EVD (p=0.005), CSF protein (p<0.001) and ICP>20mmHg (P=0.007). Both EOT IVH volume and change in IVH volume (ChgIVH) (over 1 st week) were independently associated with total CSF output (P=0.004/<0.001, respectively), and initial IVH volume (P<0.001/<0.001)). Early opening of 3 rd and 4 th ventricle (P=0.03) was associated with lower EOT volumes, while CSF protein (P=0.02), and side of EVD ipsilateral to largest IVH (P=0.04) were associated with ChgIVH. Shunting for hydrocephalus was performed in 18.6% over 1 year follow-up and was associated with higher total CSF output over first week (P<0.001). Conclusions: CSF circulation in severe IVH can be assessed by CSF output which is associated with EVD drip management and other clinical variables. EOT IVH volume and IVH volume reduction are important surrogate endpoints which are related to CSF dynamics. VP shunt requirement in spontaneous IVH is associated with early CSF output levels. These results permit future correlation of CSF output with treatment rendered (thrombolysis versus placebo) with upcoming unblinding of the trial.

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Changes in cerebrospinal fluid hydrodynamics following endoscopic third ventriculostomy for shunt-dependent noncommunicating hydrocephalus

Journal of Neurosurgery ◽

10.3171/jns.2003.98.5.1027 ◽

2003 ◽

Vol 98 (5) ◽

pp. 1027-1031 ◽

Cited By ~ 46

Author(s):

Kenichi Nishiyama ◽

Hiroshi Mori ◽

Ryuichi Tanaka

Keyword(s):

Cerebrospinal Fluid ◽

Absorptive Capacity ◽

Endoscopic Third Ventriculostomy ◽

Third Ventriculostomy ◽

Csf Dynamics ◽

Shunt System ◽

Independent State ◽

Content Type ◽

Noncommunicating Hydrocephalus ◽

Fine Print

Object. The aim of this study was to analyze physiological changes in cerebrospinal fluid (CSF) dynamics following endoscopic third ventriculostomy (ETV) for shunt-dependent noncommunicating hydrocephalus. Methods. Clinical data obtained in 15 patients treated with ETV for shunt malfunction were analyzed. Magnetic resonance imaging studies demonstrated the obstruction of the ventricular system preoperatively. After ETV, the existing shunt system was removed and a continuous extraventricular drain, set at 30 cm H2O in height, was installed to measure daily amounts of CSF outflow. Cerebrospinal fluid dynamics after ETV were also evaluated using 111In-diethylenetriamine pentaacetic acid radioisotope cisternography in six of 15 patients within 1 month of the procedure. Three patients underwent cisternography at 6 months after ETV. Cisternograms were obtained at 1, 5, 24, and 48 hours after injection of the radioisotope. To study CSF absorptive capacity, ratios of radioisotope counts at 48 and 5 hours after injection were calculated (C48:C5). Seven of 15 patients had daily outflows of CSF of less than 20 ml; this volume decreased quickly within a few days. The other eight patients demonstrated an outflow of more than 150 ml of CSF for several days, three of whom had signs of transiently increased intracranial pressure. Their CSF outflow volume decreased gradually and symptoms improved within 1 week. Ratios of C48:C5 were within normal limits in five of six patients who had undergone cisternography 1 month after ETV. These ratios were decreased in all three patients who had undergone cisternography at 6 months after ETV compared with that measured at 1 month after the procedure. Conclusions. Our data suggest that CSF dynamics convert from a shunt-dependent state to a shunt-independent state within 1 week following ETV in patients with shunt-dependent noncommunicating hydrocephalus. Nonetheless, intraventricular pressure does not decrease quickly in certain cases. Cerebrospinal fluid absorptive capacity or CSF circulation through the subarachnoid space may show further improvement several months after ETV.

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