Lumbar and ventricular CSF concentrations of extracellular matrix proteins before and after shunt surgery in idiopathic normal pressure hydrocephalus
AbstractBackgroundIdiopathic normal pressure hydrocephalus (iNPH) is a reversible CNS disease characterized by disturbed cerebrospinal fluid (CSF) dynamics. Changes in the extracellular matrix (ECM) composition might be involved in the pathophysiology of iNPH. The aim of this study was to explore possible differences between lumbar and ventricular CSF concentrations of the ECM markers brevican and neurocan, matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase-1 (TIMP-1) and their relation to clinical symptoms in iNPH patients before and after shunt surgery.MethodsPaired lumbar and ventricular CSF was ...
Source: Fluids and Barriers of the CNS - May 13, 2021 Category: Neuroscience Source Type: research

Serial Tap Test of patients with idiopathic normal pressure hydrocephalus: impact on cognitive function and its meaning
This study aimed to identify how serial punctures affect cognition to increase the sensitivity of the test and consequently the accuracy of surgical indication.MethodsSixty-one patients with INPH underwent baseline memory and executive tests repeatedly following the 2-Step Tap Test protocol (2-STT – two procedures of 30 mL lumbar CSF drainage separated by a 24-h interval). The baseline scores of INPH patients were compared with those of 55 healthy controls, and with intragroup post-puncture scores of the 2-STT.ResultsThe group with INPH had lower performance than the control group in all cognitive tests (RAVLT, ...
Source: Fluids and Barriers of the CNS - May 6, 2021 Category: Neuroscience Source Type: research

Reduction in pericyte coverage leads to blood –brain barrier dysfunction via endothelial transcytosis following chronic cerebral hypoperfusion
ConclusionsOur results indicate that reduced pericyte coverage leads to increased BBB permeability via endothelial transcytosis. Imatinib executes a protective role on the BBB integrity via inhibition of endothelial transcytosis. Maintenance of BBB integrity ameliorates brain damage through regulation of TGF- β/Smad2 signaling following CCH; therefore, reversal of BBB dysfunction may be a promising strategy for CSVD treatment. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - May 5, 2021 Category: Neuroscience Source Type: research

Exploring mechanisms of ventricular enlargement in idiopathic normal pressure hydrocephalus: a role of cerebrospinal fluid dynamics and motile cilia
In conclusion, as the CSF stroke volume at the cerebral aqueduct increases, the oscillatory shear stress increases, promoting motor cilia shedding and loss of ependymal cell coverage. These are considered to be the leading causes of ventricular enlargement in iNPH. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - April 19, 2021 Category: Neuroscience Source Type: research

Reference values for intracranial pressure and lumbar cerebrospinal fluid pressure: a systematic review
ConclusionsThis systematic review is the first to provide position-dependent reference values for intracranial pressure and lumbar cerebrospinal fluid pressure. Clinically applicable reference values for normal lumbar cerebrospinal fluid pressure were established, and are in accordance with previously used reference values. For intracranial pressure, this study strongly emphasizes the scarcity of normal pressure measures, and highlights the need for further research on the matter. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - April 13, 2021 Category: Neuroscience Source Type: research

Evaluating the cerebrospinal fluid tap test with the Hellstr öm iNPH scale for patients with idiopathic normal pressure hydrocephalus
ConclusionsThe CSF TT, with the Hellstr öm iNPH scale as the outcome measure, has clear limitations in predicting postoperative results. The gait domain may be used to predict outcomes for gait, but the balance domain is too insensitive. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - April 7, 2021 Category: Neuroscience Source Type: research

Epigenetics in blood –brain barrier disruption
AbstractThe vessels of the central nervous system (CNS) have unique barrier properties. The endothelial cells (ECs) which comprise the CNS vessels contribute to the barrier via strong tight junctions, specific transporters, and limited endocytosis which combine to protect the brain from toxins and maintains brain homeostasis. Blood –brain barrier (BBB) leakage is a serious secondary injury in various CNS disorders like stroke, brain tumors, and neurodegenerative disorders. Currently, there are no drugs or therapeutics available to treat specifically BBB damage after a brain injury. Growing knowledge in the field of e...
Source: Fluids and Barriers of the CNS - April 6, 2021 Category: Neuroscience Source Type: research

Direction and magnitude of cerebrospinal fluid flow vary substantially across central nervous system diseases
ConclusionsThe present observations provide in vivo quantitative evidence for substantial variation in direction and magnitude of CSF flow, with re-direction of aqueductal flow in communicating hydrocephalus, and significant extra-cranial CSF production. The grading of ventricular reflux of tracer shows promise as a clinical useful method to assess CSF flow pattern disturbances in patients.Graphic abstract (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - April 1, 2021 Category: Neuroscience Source Type: research

Microglia activated by microbial neuraminidase contributes to ependymal cell death
AbstractThe administration of microbial neuraminidase into the brain ventricular cavities of rodents represents a model of acute aseptic neuroinflammation. Ependymal cell death and hydrocephalus are unique features of this model. Here we demonstrate that activated microglia participates in ependymal cell death. Co-cultures of pure microglia with ependymal cells (both obtained from rats) were performed, and neuraminidase or lipopolysaccharide were used to activate microglia. Ependymal cell viability was unaltered in the absence of microglia or inflammatory stimulus (neuraminidase or lipopolysaccharide). The constitutive exp...
Source: Fluids and Barriers of the CNS - March 23, 2021 Category: Neuroscience Source Type: research

Neural crest cell-derived pericytes act as pro-angiogenic cells in human neocortex development and gliomas
AbstractCentral nervous system diseases involving the parenchymal microvessels are frequently associated with a ‘microvasculopathy’, which includes different levels of neurovascular unit (NVU) dysfunction, including blood–brain barrier alterations. To contribute to the understanding of NVU responses to pathological noxae, we have focused on one of its cellular components, the microvascular pericytes, hi ghlighting unique features of brain pericytes with the aid of the analyses carried out during vascularization of human developing neocortex and in human gliomas. Thanks to their position, centred within th...
Source: Fluids and Barriers of the CNS - March 20, 2021 Category: Neuroscience Source Type: research

Astrocyte-specific hypoxia-inducible factor 1 (HIF-1) does not disrupt the endothelial barrier during hypoxia in vitro
ConclusionsThis study demonstrates that AC HIF-1 dependent paracrine signaling does not contribute to AC modulation of EC barrier function under normoxic or hypoxic conditions. Thus other cell types likely mediate EC permeability in stress scenarios. Our data does however highlight the continuous protective effect of AC on the barrier endothelium. Exploring these protective mechanisms in more detail will provide essential insight into ways to prevent barrier disturbance during injury and disease. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - March 18, 2021 Category: Neuroscience Source Type: research

In vitro evaluation of cerebrospinal fluid velocity measurement in type I Chiari malformation: repeatability, reproducibility, and agreement using 2D phase contrast and 4D flow MRI
ConclusionAgreement, repeatability, and reproducibility of 2D PC MRI and 4D Flow detection of peak CSF velocities was quantified using a patient-specific in vitro model of Chiari malformation. In combination, the greatest factor leading to measurement inconsistency was determined to be a lack of reproducibility between different MRI centers. Overall, these findings may help lead to better understanding for application of 2D PC MRI and 4D Flow techniques as diagnostic tools for CSF dynamics quantification in Chiari malformation and related diseases. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - March 18, 2021 Category: Neuroscience Source Type: research

Variations in the cerebrospinal fluid dynamics of the American alligator ( Alligator mississippiensis )
ConclusionsMost of the CSF flow dynamics recorded from the alligators, are similar to what has been reported from studies of the human CSF. It is hypothesized that the link between ventilatory mechanics and CSF pulsations in the alligator is mediated by displacement of the spinal dura. The results of the study suggest that understanding the CSF dynamics ofAlligator may provide unique insights into the evolutionary origins and functional regulation of the human CSF dynamics. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - March 12, 2021 Category: Neuroscience Source Type: research

Protecting P-glycoprotein at the blood –brain barrier from degradation in an Alzheimer’s disease mouse model
ConclusionsThese findings provide in vivo evidence that microtubule inhibition maintains P-gp protein expression and transport activity levels, which in turn helps to lower hA β brain levels in hAPP mice. Thus, protecting P-gp at the blood-brain barrier may provide a novel therapeutic strategy for AD and other Aβ-based pathologies. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - March 6, 2021 Category: Neuroscience Source Type: research

Are CSF CXCL13 concentrations solely dependent on intrathecal production? A commentary on “Chemokine CXCL13 in serum, CSF, and blood–CSF barrier function”
In conclusion, we argue that for patients with moderately elevated CSF CXCL13 concentrations, serum CXCL13 concentrations influence CSF CXCL13 levels, and thus the appropriate correc tions including incorporation of CSF/serum ratios and Qalbumin values should be utilized. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - February 25, 2021 Category: Neuroscience Source Type: research

Quantification of arterial, venous, and cerebrospinal fluid flow dynamics by magnetic resonance imaging under simulated micro-gravity conditions: a prospective cohort study
ConclusionsThese results collectively demonstrate that acute application of −15° HDT caused a reduction in CSF flow variables (systolic peak flow and peak-to-peak pulse amplitude) which, when coupled with a decrease in average cerebral arterial flow, systolic peak flow, and peak-to-peak pulse amplitude, is consistent with a decrease in cardiac-related pulsatile CSF flow. These results suggest that decreases in cerebral arterial inflow were the principal drivers of decreases in CSF pulsatile flow. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - February 12, 2021 Category: Neuroscience Source Type: research

Circulating tight-junction proteins are potential biomarkers for blood –brain barrier function in a model of neonatal hypoxic/ischemic brain injury
ConclusionsLevels of circulating claudin-5 and occludin are increased after hypoxic/ischemic brain injuries and blood –brain barrier-impairment and have promise as early biomarkers for cerebral vascular dysfunction and as a tool for risk assessment of neonatal brain injuries. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - February 10, 2021 Category: Neuroscience Source Type: research

Transfer of rhodamine-123  into the brain and cerebrospinal fluid of fetal, neonatal and adult rats
AbstractBackgroundAdenosine triphosphate binding cassette transporters such as P-glycoprotein (PGP) play an important role in drug pharmacokinetics by actively effluxing their substrates at barrier interfaces, including the blood-brain, blood-cerebrospinal fluid (CSF) and placental barriers. For a molecule to access the brain during fetal stages it must bypass efflux transporters at both the placental barrier and brain barriers themselves. Following birth, placental protection is no longer present and brain barriers remain the major line of defense. Understanding developmental differences that exist in the transfer of PGP ...
Source: Fluids and Barriers of the CNS - February 8, 2021 Category: Neuroscience Source Type: research

The relationship between cerebral blood flow and venous sinus pressure: can hyperemia induce idiopathic intracranial hypertension?
ConclusionsThe cerebral venous sinus blood flow and pressure response relationship are quadratic in nature, with the major cause of this being the degree of rotation induced in the flow. The elevated blood flow found in children with IIH can explain the increased ICP that is found, secondary to the increase in venous pressure that develops. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - February 4, 2021 Category: Neuroscience Source Type: research

Cerebrospinal fluid biomarkers of neuroinflammation in children with hydrocephalus and shunt malfunction
AbstractBackgroundApproximately 30% of cerebrospinal fluid (CSF) shunt systems for hydrocephalus fail within the first year and 98% of all patients will have shunt failure in their lifetime. Obstruction remains the most common reason for shunt failure. Previous evidence suggests elevated pro-inflammatory cytokines in CSF are associated with worsening clinical outcomes in neuroinflammatory diseases. The aim of this study was to determine whether cytokines and matrix metalloproteinases (MMPs) contribute towards shunt failure in hydrocephalus.MethodsUsing multiplex ELISA, this study examined shunt failure through the CSF prot...
Source: Fluids and Barriers of the CNS - January 29, 2021 Category: Neuroscience Source Type: research

Presence of a mutation in PSEN1 or PSEN2 gene is associated with an impaired brain endothelial cell phenotype in vitro
ConclusionsOur study reports that iPSC-derived BMECs obtained from FAD patients showed impaired barrier properties and BMEC metabolism. In particular, mutation in thePSEN1 gene was associated with a more detrimental phenotype than mutation inPSEN2, as noted by a reduced barrier function, reduced drug efflux pump activity, and diminished glucose metabolism. Therefore, assessing the contribution of genetic mutations associated with Alzheimer ’s disease will allow us to better understand the contribution of the BBB in dementia, but also other neurodegenerative diseases. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - January 7, 2021 Category: Neuroscience Source Type: research

Structural disruption of the blood –brain barrier in repetitive primary blast injury
ConclusionThis study provides analysis of the BBB components after repetitive blast injury. These results will be critical as preventative and therapeutic strategies are established for veterans recovering from blast-induced traumatic brain injury. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - January 7, 2021 Category: Neuroscience Source Type: research

Disparate volumetric fluid shifts across cerebral tissue compartments with two different anesthetics
ConclusionsWe demonstrated CSF volume expansion with DEXM-I (in comparison to ISO) and parenchymal (GM) expansion with ISO (in comparison to DEXM-I), which may explain the differences in glymphatic transport. The T2* changes in ISO are suggestive of an increased bioenergetic state associated with excess cellular firing/bursting when compared to DEXM-I. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - January 6, 2021 Category: Neuroscience Source Type: research

In Xenopus ependymal cilia drive embryonic CSF circulation and brain development independently of cardiac pulsatile forces
ConclusionsOur data support a paradigm in which  Xenopus embryonic ventriculogenesis and rostral brain development are critically dependent on ependymal cilia-driven CSF flow currents that are generated independently of cardiac pulsatile forces. Our work suggests that the Xenopus ventricular system forms a complex cilia-driven CSF flow network which regulates neural cell organization. This work will redirect efforts to understand the molecular regulators of embryonic CSF flow by focusing attention on motile cilia rather than other forces relevant only to the adult. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - December 11, 2020 Category: Neuroscience Source Type: research

Cerebrospinal fluid drainage kinetics across the cribriform plate are reduced with aging
ConclusionsCollectively, these data show that the main CSF outflow sites were the nasal region across the cribriform plate and from the spinal regions in mice. In young adult mice, the contribution of the nasal and cribriform route to outflow was much higher than from the spinal regions. In older mice, the contribution of the nasal route to CSF outflow was reduced significantly but not for the spinal routes. This kinetic approach may have significance in determining early changes in CSF drainage in neurological disorder, age-related cognitive decline and brain diseases. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - November 30, 2020 Category: Neuroscience Source Type: research

Water treadmill training attenuates blood-spinal cord barrier disruption in rats by promoting angiogenesis and inhibiting matrix metalloproteinase-2/9 expression following spinal cord injury
ConclusionsThe results of this study indicate that TT promotes functional recovery for the following reasons: TT (1) protects residual BSCB structure from further damage, (2) promotes vascular regeneration, and (3) inhibits MMP-2/9 expression to mitigate BSCB damage. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - November 25, 2020 Category: Neuroscience Source Type: research

A blood –brain barrier overview on structure, function, impairment, and biomarkers of integrity
AbstractThe blood –brain barrier is playing a critical role in controlling the influx and efflux of biological substances essential for the brain’s metabolic activity as well as neuronal function. Thus, the functional and structural integrity of the BBB is pivotal to maintain the homeostasis of the brain microenv ironment. The different cells and structures contributing to developing this barrier are summarized along with the different functions that BBB plays at the brain–blood interface. We also explained the role of shear stress in maintaining BBB integrity. Furthermore, we elaborated on the clinical a...
Source: Fluids and Barriers of the CNS - November 18, 2020 Category: Neuroscience Source Type: research

Ex-vivo quantification of ovine pia arachnoid complex biomechanical properties under uniaxial tension
AbstractBackgroundThe pia arachnoid complex (PAC) is a cerebrospinal fluid-filled tissue conglomerate that surrounds the brain and spinal cord. Pia mater adheres directly to the surface of the brain while the arachnoid mater adheres to the deep surface of the dura mater. Collagen fibers, known as subarachnoid trabeculae (SAT) fibers, and microvascular structure lie intermediately to the pia and arachnoid meninges. Due to its structural role, alterations to the biomechanical properties of the PAC may change surface stress loading in traumatic brain injury (TBI) caused by sub-concussive hits. The aim of this study was to qua...
Source: Fluids and Barriers of the CNS - November 12, 2020 Category: Neuroscience Source Type: research

Sex difference in cerebrospinal fluid/blood albumin quotients in patients with schizophreniform and affective psychosis
AbstractBackgroundThe importance of cerebrospinal fluid (CSF) diagnostics for psychiatry is growing. The CSF/blood albumin quotient (QAlb) is considered to be a measure of the blood –CSF barrier function. Recently, systematically higher QAlb in males than in females was described in neurological patients. The aim of this study was to investigate whether a sex difference could also be detected in a well-characterized psychiatric cohort.MethodsThe patient cohort comprised 989 patients, including 545 females and 444 males with schizophreniform and affective syndromes who underwent CSF diagnostics, including QAlb measure...
Source: Fluids and Barriers of the CNS - November 11, 2020 Category: Neuroscience Source Type: research

Permeability of the windows of the brain: feasibility of dynamic contrast-enhanced MRI of the circumventricular organs
ConclusionsCurrent measurements confirm the often-held assumption of highly permeable CVOs, of which the secretory types have the strongest blood-to-brain transfer. The current study suggests that DCE MRI could be a promising technique to further assess the function of the CVOs and how pathogens can potentially enter the brain via these structures.Trial registration: Netherlands Trial Register number: NL6358, date of registration: 2017-03-24 (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - October 28, 2020 Category: Neuroscience Source Type: research

Cerebrospinal fluid analysis in 108 patients with progressive multifocal leukoencephalopathy
AbstractBackgroundProgressive multifocal leukoencephalopathy (PML) is caused by an opportunistic infection with JC polyoma virus (JCPyV) and mainly affects immunocompromised patients. It leads to pronounced demyelination of the central nervous system (CNS) resulting in severe disability or even death. Detection of JCPyV DNA in the cerebrospinal fluid (CSF) is usually accepted as proof for the diagnosis of PML. Routine CSF parameters, like CSF cell count, protein concentration, Qalbumin, or intrathecal immunoglobulin synthesis are mostly considered normal. However, this has not been investigated systematically.MethodsWe ana...
Source: Fluids and Barriers of the CNS - October 27, 2020 Category: Neuroscience Source Type: research

Commentary on human pluripotent stem cell-based blood –brain barrier models
AbstractIn 2012, we provided the first published evidence that human pluripotent stem cells could be differentiated to cells exhibiting markers and phenotypes characteristic of the blood –brain barrier (BBB). In the ensuing years, the initial protocols have been refined, and the research community has identified both positive and negative attributes of this stem cell-based BBB model system. Here, we give our perspective on the current status of these models and their use in the BB B community, as well as highlight key attributes that would benefit from improvement moving forward. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - October 19, 2020 Category: Neuroscience Source Type: research

Comparative investigation of different telemetric methods for measuring intracranial pressure: a prospective pilot study
ConclusionICP measurements with both systems continuously showed synchronous absolute ICP values, however absolute values of ICP measurement with the different systems did not match. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - October 17, 2020 Category: Neuroscience Source Type: research

Identification and in vivo characterization of a brain-penetrating nanobody
ConclusionThis method led to the discovery of an anti-transferrin receptor nanobody that can reach the brain via receptor-mediated transcytosis after peripheral administration. This method could be used to assess novel proteins for brain-penetrating capabilities using a target-engaging readout. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - October 14, 2020 Category: Neuroscience Source Type: research

LC –MS/MS-based in vitro and in vivo investigation of blood–brain barrier integrity by simultaneous quantitation of mannitol and sucrose
ConclusionsWe established a highly sensitive, specific and reproducible approach to simultaneously measure the BBB permeability of two classical low molecular weight, hydrophilic markers in a stable isotope labeled format. This method is now available as a tool to quantify BBB permeability in vitro and in vivo in different disease models, as well as for monitoring treatment outcomes. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - October 14, 2020 Category: Neuroscience Source Type: research

The microvascular extracellular matrix in brains with Alzheimer ’s disease neuropathologic change (ADNC) and cerebral amyloid angiopathy (CAA)
ConclusionsCortical MV density and diameter are not appreciably altered by ADNC or CAA. TSG-6 and HA are increased in both ADNC and CAA, with laminin and col IV decreased in the BM of high ADNC, but laminin increased in moderate-severe CAA. These results show that changes in the ECM occur in AD and CAA, but independently of one another, and likely reflect on the regional functioning of the brain microvasculature. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - September 28, 2020 Category: Neuroscience Source Type: research

The incidence of obesity, venous sinus stenosis and cerebral hyperaemia in children referred for MRI to rule out idiopathic intracranial hypertension at a tertiary referral hospital: a 10  year review
AbstractBackgroundChildren referred to a tertiary hospital for the indication, “rule out idiopathic intracranial hypertension (IIH)” may have an increased risk of raised venous sinus pressure. An increase in sinus pressure could be due to obesity, venous outflow stenosis or cerebral hyperemia. The purpose of this paper is to define the incidence of each of these variables in these children.MethodsFollowing a data base review, 42 children between the ages of 3 and 15  years were found to have been referred over a 10 year period. The body mass index was assessed. The cross sectional areas and circumfere...
Source: Fluids and Barriers of the CNS - September 28, 2020 Category: Neuroscience Source Type: research

Non-invasive measurement of choroid plexus apparent blood flow with arterial spin labeling
AbstractBackgroundThe choroid plexus is a major contributor to the generation of cerebrospinal fluid (CSF) and the maintenance of its electrolyte and metabolite balance. Here, we sought to characterize the blood flow dynamics of the choroid plexus using arterial spin labeling (ASL) MRI to establish ASL as a non-invasive tool for choroid plexus function and disease studies.MethodsSeven healthy volunteers were imaged on a 3T MR scanner. ASL images were acquired with 12 labeling durations and post labeling delays. Regions of the choroid plexus were manually segmented on high-resolution T1 weighted images. Choroid plexus perfu...
Source: Fluids and Barriers of the CNS - September 21, 2020 Category: Neuroscience Source Type: research

Diabetes is associated with familial idiopathic normal pressure hydrocephalus: a case –control comparison with family members
ConclusionsDiabetes is associated with fNPH and a possible risk factor for fNPH. Diabetes could contribute to the pathogenesis of iNPH/fNPH, which motivates to further prospective and gene-environmental studies to decipher the disease modelling of iNPH/fNPH. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - September 14, 2020 Category: Neuroscience Source Type: research

David S. Miller: Scientist, Mentor, Friend —a tribute and thank you
AbstractDavid S. Miller was Acting Scientific Director of the Division of Intramural Research at the National Institute of Environmental Health Sciences, National Institutes of Health, and Head of the Intracellular Regulation Group in the Laboratory of Toxicology and Pharmacology before he retired in 2016. David received his Ph.D. in biochemistry from the University of Maine in 1973. David was a Group Leader at the Michigan Cancer Foundation before joining the NIEHS in 1985. His research covered a wide range from renal excretory transport mechanisms to regulation of transporters at the blood –CSF and blood–brai...
Source: Fluids and Barriers of the CNS - September 13, 2020 Category: Neuroscience Source Type: research

The potential role of microvascular pathology in the neurological manifestations of coronavirus infection
We present the hypothesis that pre-existing vascular damage (due to aging, cardiovascular disease, diabetes, hypertension or other conditions) facilitates infiltration of the virus into the central nervous system (CNS), increasing neuro-inflammation and the likelihood o f neurological symptoms. We also discuss the role of a neuroinflammatory cytokine profile in both blood–brain barrier dysfunction and macrovascular disease (e.g. ischemic stroke and thromboembolism). Future studies are needed to better understand the involvement of the microvasculature in coronavi rus neuropathology, and to test the diagnostic potenti...
Source: Fluids and Barriers of the CNS - September 9, 2020 Category: Neuroscience Source Type: research

Chemically defined human vascular laminins for biologically relevant culture of hiPSC-derived brain microvascular endothelial cells
ConclusionLN 511 improves the functionality and long-term barrier stability of iBMECs. Our findings suggest that incorporation of physiologically relevant LN 511 in iBMEC culture would be beneficial for disease modeling applications and BBB-on-a-chip platforms that accommodate fluid flow. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - September 9, 2020 Category: Neuroscience Source Type: research

A face-to-face comparison of claudin-5 transduced human brain endothelial (hCMEC/D3) cells with porcine brain endothelial cells as blood –brain barrier models for drug transport studies
ConclusionsThe claudin-5 transduced hCMEC/D3 cells provide a tool to studying the contribution of claudin-5 to barrier tightness and how this can be further enhanced by additional transfections or other manipulations of this widely used in vitro model of the BBB. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - August 25, 2020 Category: Neuroscience Source Type: research

Functional hyperemia drives fluid exchange in the paravascular space
AbstractThe brain lacks a conventional lymphatic system to remove metabolic waste. It has been proposed that directional fluid movement through the arteriolar paravascular space (PVS) promotes metabolite clearance. We performed simulations to examine if arteriolar pulsations and dilations can drive directional CSF flow in the PVS and found that arteriolar wall movements do not drive directional CSF flow. We propose an alternative method of metabolite clearance from the PVS, namely fluid exchange between the PVS and the subarachnoid space (SAS). In simulations with compliant brain tissue, arteriolar pulsations did not drive...
Source: Fluids and Barriers of the CNS - August 19, 2020 Category: Neuroscience Source Type: research

Advancing brain barriers RNA sequencing: guidelines from experimental design to publication
ConclusionNext generation transcriptomic profiling of the brain barriers provides a novel resource for understanding the development, function and pathology of these barrier cells, which is essential for understanding CNS homeostasis and disease. Continuous advancement and sophistication of RNA-Seq will require interdisciplinary approaches between brain barrier researchers and bioinformaticians as successfully performed in BtRAIN. The present guidelines are built on the BtRAIN interdisciplinary experience and aim to facilitate collaboration of brain barriers researchers with bioinformaticians to advance RNA-Seq study desig...
Source: Fluids and Barriers of the CNS - August 17, 2020 Category: Neuroscience Source Type: research

Chronic extradural compression of spinal cord leads to syringomyelia in rat model
ConclusionExtradural blockade of CSF flow can induce syringomyelia in rats. Temporary locomotor deficit occurred in some rats. This reproducible rat model of syringomyelia, which mimics syringomyelia in humans, can provide a good model for the study of disease mechanisms and therapies. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - July 30, 2020 Category: Neuroscience Source Type: research

Location matters: highly divergent protein levels in samples from different CNS compartments in a clinical trial of rituximab for progressive MS
ConclusionA substantial heterogeneity in the protein levels of samples obtained from different CNS compartments was seen. Therefore, data obtained from analysis of lumbar CSF should be interpreted with caution when making conclusions about pathophysiological processes in brain tissue. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - July 28, 2020 Category: Neuroscience Source Type: research

Contribution of brain pericytes in blood –brain barrier formation and maintenance: a transcriptomic study of cocultured human endothelial cells derived from hematopoietic stem cells
AbstractFormation, maintenance, and repair of the blood –brain barrier (BBB) are critical for central nervous system homeostasis. The interaction of endothelial cells (ECs) with brain pericytes is known to induce BBB characteristics in brain ECs during embryogenesis and can be used to differentiate human ECs from stem cell source in in vitro BBB models . However, the molecular events involved in BBB maturation are not fully understood. To this end, human ECs derived from hematopoietic stem cells were cultivated with either primary bovine or cell line-derived human brain pericytes to induce BBB formation. Subsequently...
Source: Fluids and Barriers of the CNS - July 27, 2020 Category: Neuroscience Source Type: research

Differential expression of receptors mediating receptor-mediated transcytosis (RMT) in brain microvessels, brain parenchyma and peripheral tissues of the mouse and the human
This study provides a molecular transcriptomics map of key RMT receptors in mouse and human brain microvessels and peripheral tissues, important to translational studies of biodistribution, efficacy and safety of antibodies developed against these receptors. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - July 21, 2020 Category: Neuroscience Source Type: research

Preterm intraventricular hemorrhage in vitro: modeling the cytopathology of the ventricular zone
DiscussionThis protocol will allow investigators to test cytopathological mechanisms contributing to the pathology of IVH with high temporal resolution and query the impact of injury to the maturation of the VZ. This technique recapitulates features of normal maturation of the VZ in vitro, offering the capacity to investigate the developmental features of VZ biogenesis. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - July 19, 2020 Category: Neuroscience Source Type: research