Identification of key molecular biomarkers involved in reactive and neurodegenerative processes present in inherited congenital hydrocephalus
ConclusionOur results identify possible biomarkers of hydrocephalus in the cerebral grey and white matter. In the white matter, OPCs could be reacting to acquire a neuroprotective role or as a delay in the oligodendrocyte maturation. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - July 2, 2021 Category: Neuroscience Source Type: research

Increased extracellular fluid is associated with white matter fiber degeneration in CADASIL: in vivo evidence from diffusion magnetic resonance imaging
ConclusionsOur study demonstrated that increased ECF was associated with WM degeneration and the occurrence of lacunes and microbleeds, providing important new insights into the role of ECF in CADASIL pathology. Improving  ECF drainage might become a therapeutic strategy in future. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - June 30, 2021 Category: Neuroscience Source Type: research

Comparative assessment of in vitro BBB tight junction integrity following exposure to cigarette smoke and e-cigarette vapor: a quantitative evaluation of the protective effects of metformin using small-molecular-weight paracellular markers
ConclusionIn agreement with previous studies, our data showed the metformin could counteract the negative impact of TS and EC on BBB integrity, thus suggesting the possibility of repurposing this drug to afford cerebrovascular protection. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - June 22, 2021 Category: Neuroscience Source Type: research

Brain endothelial LRP1 maintains blood –brain barrier integrity
AbstractThe entry of blood-borne molecules into the brain is restricted by the blood –brain barrier (BBB). Various physical, transport and immune properties tightly regulate molecule movement between the blood and the brain to maintain brain homeostasis. A recent study utilizing a pan-endothelial, constitutiveTie2-Cre showed that paracellular passage of blood proteins into the brain is governed by endocytic and cell signaling protein low-density lipoprotein receptor –related protein 1 (LRP1). Taking advantage of conditionalSlco1c1-CreERT2 specific to CNS endothelial cells and choroid plexus epithelial cells we now supp...
Source: Fluids and Barriers of the CNS - June 19, 2021 Category: Neuroscience Source Type: research

Brain pharmacokinetics of two BBB penetrating bispecific antibodies of different size
ConclusionA smaller size and lower TfR1 avidity are likely important for fast parenchymal delivery, while elimination of brain-associated bispecific antibodies may not be dependent on these characteristics. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - June 2, 2021 Category: Neuroscience Source Type: research

Intracranial pressure waveform characteristics in idiopathic normal pressure hydrocephalus and late-onset idiopathic aqueductal stenosis
ConclusionsICP is higher in LIAS than in iNPH patients, likely due to the chronically obstructed CSF flow through the aqueduct, but still in a range considered normal. Interestingly, AMP/MWA was higher in iNPH patients, suggesting a possible role of high ICP pulse pressure amplitudes in iNPH pathophysiology. Cerebrospinal reserve capacity and intracranial compliance is impaired in both groups and the pressure-volume relationship might be shifted towards lower ICP values in iNPH. The physiological influence of age on ICP and AMP/MWA requires further research. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - May 26, 2021 Category: Neuroscience Source Type: research

Brain Barriers and brain fluids research in 2020 and the fluids and barriers of the CNS thematic series on advances in in vitro modeling of the blood –brain barrier and neurovascular unit
AbstractThis editorial discusses advances in brain barrier and brain fluid research in 2020. Topics include: the cerebral endothelium and the neurovascular unit; the choroid plexus; the meninges; cerebrospinal fluid and the glymphatic system; disease states impacting the brain barriers and brain fluids; drug delivery to the brain. This editorial also highlights the recently completedFluids Barriers CNS thematic series entitled, ‘Advances in in vitro modeling of the blood–brain barrier and neurovascular unit’. Such in vitro modeling is progressing rapidly. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - May 21, 2021 Category: Neuroscience Source Type: research

Lumbar and ventricular CSF concentrations of extracellular matrix proteins before and after shunt surgery in idiopathic normal pressure hydrocephalus
ConclusionLevels of the CNS-specific proteins brevican and neurocan did not differ between the lumbar and ventricular CSF, whereas the increase of several CNS-unspecific MMPs and TIMP-1 in lumbar CSF suggests contribution from peripheral tissues. The increase of ECM proteins in CSF following shunt surgery could indicate disturbed ECM dynamics in iNPH that are restored by restitution of CSF dynamics. (Source: Fluids and Barriers of the CNS)
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
ConclusionProgressive cognitive improvement occurred over the 2-STT and changes were more significant after the second LP in all cognitive domains except for RAVLT (A7). Encephalic alert system ‘arousal’ seems to participate in early improvements observed during 2-STT. The second LP increased the sensitivity of the drainage test to detect changes in cognitive variables, and consequently improved the quality of the method. (Source: Fluids and Barriers of the CNS)
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 epige...
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