Higher levels of neurofilament light chain and total tau in CSF are associated with negative outcome after shunt surgery in patients with normal pressure hydrocephalus
ConclusionsHigher levels of T-tau and NfL were associated with a less favorable response to shunt surgery, suggesting a more active neurodegeneration in this group of patients. However, CSF levels of these biomarkers can be elevated also in patients who respond to shunt surgery. Thus, none of these CSF biomarkers, alone or used in combination, are suitable for excluding patients from surgery. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - February 14, 2022 Category: Neuroscience Source Type: research

CNS endothelial derived extracellular vesicles are biomarkers of active disease in multiple sclerosis
Conclusions: For the first time, we have identified a method to identify CNS endothelial derived EV in circulation from human blood samples. Results from our pilot study indicate that increased levels of CNS endothelial derived EV may be a biomarker of BBB permeability and active dise ase in MS. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - February 8, 2022 Category: Neuroscience Source Type: research

Changes in intrathoracic pressure, not arterial pulsations, exert the greatest effect on tracer influx in the spinal cord
ConclusionsIntrathoracic pressure changes that occur over the respiratory cycle, particularly decreased intrathoracic pressures generated during inspiration, have a profound effect on tracer movement after injection into spinal CSF and increase cord parenchymal tracer influx. Arterial pulsations likely drive fluid transport from perivascular spaces into the surrounding interstitium, but their overall impact is less than that of the respiratory cycle on net tracer influx. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - February 8, 2022 Category: Neuroscience Source Type: research

Prolonged culturing of iPSC-derived brain endothelial-like cells is associated with quiescence, downregulation of glycolysis, and resistance to disruption by an Alzheimer ’s brain milieu
ConclusioniBECs can be used to study responses to disease-relevant stimuli in proliferating vs. more quiescent endothelial cell states, which may provide insight into BBB vulnerabilities in contexts of development, brain injury, and neurodegenerative disease. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - February 5, 2022 Category: Neuroscience Source Type: research

k-Shape clustering for extracting macro-patterns in intracranial pressure signals
ConclusionsWe provide the starting point for future researchers to use a computational approach to characterize ICP recordings from a wide cohort of disorders. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - February 5, 2022 Category: Neuroscience Source Type: research

Cerebrospinal fluid biomarkers that reflect clinical symptoms in idiopathic normal pressure hydrocephalus patients
ConclusionsCSF biomarkers of neurodegeneration appeared to correlate with pre- and postoperative cognition, providing a window into neuropathological processes. In addition, preoperative CSF neurodegeneration biomarkers may have potential in the prediction of gait and cognitive outcomes after shunt surgery. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - February 5, 2022 Category: Neuroscience Source Type: research

The glymphatic hypothesis: the theory and the evidence
AbstractThe glymphatic hypothesis proposes a mechanism for extravascular transport into and out of the brain of hydrophilic solutes unable to cross the blood –brain barrier. It suggests that there is a circulation of fluid carrying solutes inwards via periarterial routes, through the interstitium and outwards via perivenous routes. This review critically analyses the evidence surrounding the mechanisms involved in each of these stages. There is good ev idence that both influx and efflux of solutes occur along periarterial routes but no evidence that the principal route of outflow is perivenous. Furthermore, periarterial ...
Source: Fluids and Barriers of the CNS - February 3, 2022 Category: Neuroscience Source Type: research

Human in silico trials for parametric computational fluid dynamics investigation of cerebrospinal fluid drug delivery: impact of injection location, injection protocol, and physiology
ConclusionThe computational modeling approach provides ability to conduct in silico trials representative of CSF injection protocols. Taken together, the findings indicate a strong potential for delivery protocols to be optimized to reach a target region(s) of the spine and/or brain with a needed therapeutic dose. Parametric modification of bolus rate/volume and flush volume was found to have impact on tracer distribution; albeit to a smaller degree than injection location, with CM and ICV injections resulting in greater therapeutic dose to brain regions compared to LP. CSF stroke volume and frequency both played an import...
Source: Fluids and Barriers of the CNS - January 28, 2022 Category: Neuroscience Source Type: research

Met-RANTES preserves the blood –brain barrier through inhibiting CCR1/SRC/Rac1 pathway after intracerebral hemorrhage in mice
ConclusionsOur findings demonstrate that CCR5 inhibition by Met-R improves neurological deficits after ICH by preserving BBB integrity through inhibiting CCR1/SRC/Rac1 signaling pathway in mice. Thus, Met-R has therapeutic potential in the management of ICH patients. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - January 21, 2022 Category: Neuroscience Source Type: research

Pericyte, but not astrocyte, hypoxia inducible factor-1 (HIF-1) drives hypoxia-induced vascular permeability in vivo
ConclusionThis study shows that pericyte but not astrocyte HIF-1 stabilization modulates endothelial tight junction functionality and thereby plays a pivotal role in hypoxia-induced vascular dysfunction. Whether the cells respond similarly or differentially to other injury stimuli will be of significant relevance. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - January 15, 2022 Category: Neuroscience Source Type: research

Chronic effects of blast injury on the microvasculature in a transgenic mouse model of Alzheimer ’s disease related Aβ amyloidosis
ConclusionIn conditions of high brain concentrations of human A β, bTBI exposure results in reduced AQP4 expression at the astroglia-microvascular interface, and in chronic capillary proliferation like what has been reported in AD. Long term microvascular changes after bTBI may contribute to the risk for developing chronic neurodegenerative disease later in lif e. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - January 10, 2022 Category: Neuroscience Source Type: research

The timed up and go test in idiopathic normal pressure hydrocephalus: a Nationwide Study of 1300 patients
ConclusionsThis study establishes the distribution of TUG in iNPH patients and shows that the test captures important clinical features that improve after surgery independent of sex and in all age groups, confirming the clinical value of the TUG test. TUG performance is associated with performance on the 10MWT pre- and post-operatively. However, the weak correlations in post-operative change to the 10MWT and other established outcome measures indicate an additional value of TUG when assessing the effects of shunt surgery. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - January 10, 2022 Category: Neuroscience Source Type: research

Facilitating drug delivery in the central nervous system by opening the blood-cerebrospinal fluid barrier with a single low energy shockwave pulse
ConclusionThis is the first study to demonstrate and validate a method for noninvasively and selectively opening the BCSFB to enhance drug delivery into CSF circulation. Potential applications may include treatments for neurodegenerative diseases, CNS infections, brain tumors, and leptomeningeal carcinomatosis. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - January 6, 2022 Category: Neuroscience Source Type: research

Hypoxia increases expression of selected blood –brain barrier transporters GLUT-1, P-gp, SLC7A5 and TFRC, while maintaining barrier integrity, in brain capillary endothelial monolayers
ConclusionsOur findings collectively suggest that hypoxic conditions increase some BBB transporters' expression via HIF-1 α stabilization, without compromising monolayer integrity. This may in part explain why brain capillaries show early maturation, in terms of barrier tightness and protein expression, during embryogenesis, and provides a novel methodological tool for optimal brain endothelial culture. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - January 4, 2022 Category: Neuroscience Source Type: research

Intercompartmental communication between the cerebrospinal and adjacent spaces during intrathecal infusions in an acute ovine in-vivo model
ConclusionsStandardized infusion tests with multi-compartmental pressure recordings in sheep have helped capture distinct reactions between the intrathecal, intracranial, arterial, and venous systems. Volumetric pressure changes in the intrathecal space have been shown to propagate to the intraventricular and arterial systems in our sample, and to the venous side in individual cases. These results represent an important step into achieving a more complete quantitative understanding of how an acute rise in intrathecal pressure can propagate and influence other systems. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - January 4, 2022 Category: Neuroscience Source Type: research