Characterization of passive permeability after low intensity focused ultrasound mediated blood –brain barrier disruption in a preclinical model
ConclusionThe magnitude of LiFUS mediated BBB opening correlates with concentration of microbubbles, cavitation dose as well as time of tracer administration post-sonication. These data help define the window of maximal BBB opening and applicable sonication parameters on a clinically translatable and commercially available FUS system that can be used to improve passive permeability and accumulation of therapeutics targeting the brain. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - September 8, 2022 Category: Neuroscience Source Type: research
ROS attenuates TET2-dependent ZO-1 epigenetic expression in cerebral vascular endothelial cells
ConclusionsThese findings suggest that TET activity is essential in regulating ZO-1 expression of BBB. It might be a potential target for neuroprotection during aging and in diverse neurological conditions. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - September 8, 2022 Category: Neuroscience Source Type: research
In vivo assessment of Lewy body and beta-amyloid copathologies in idiopathic normal pressure hydrocephalus: prevalence and associations with clinical features and surgery outcome
ConclusionsPrevalent LB- and AD-related neurodegenerative pathologies affect a significant proportion of iNPH patients and contribute to cognitive decline (both) and motor impairment (only LB pathology) but do not significantly influence the surgical outcome at 6 months. Their effect on the clinical benefit after surgery over a more extended period remains to be determined. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - September 7, 2022 Category: Neuroscience Source Type: research
Lysophosphatidic acid as a CSF lipid in posthemorrhagic hydrocephalus that drives CSF accumulation via TRPV4-induced hyperactivation of NKCC1
ConclusionsTogether, our data reveal that a serum lipid present in brain pathologies with hemorrhagic events promotes CSF hypersecretion and ensuing brain water accumulation via its direct action on TRPV4 and its downstream regulation of NKCC1. TRPV4 may therefore be a promising future pharmacological target for pathologies involving brain water accumulation. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - September 6, 2022 Category: Neuroscience Source Type: research
Activation of NMDA receptors in brain endothelial cells increases transcellular permeability
In this study, we hypothesized that N-methyl-D-aspartate (NMDA) receptor signaling, the most well characterized neurotransmitter signaling system which regulates delivery of essential molecules through the blood –brain barrier (BBB). Upon application of NMDA in both in vitro and in vivo models, increased delivery of bioactive molecules that was mediated through modulation of molecules involved in molecular delivery, including clathrin and caveolin were observed. Also, NMDA activation induced structural ch anges in the BBB and increased transcellular permeability that showed regional heterogeneity in its responses. Moreov...
Source: Fluids and Barriers of the CNS - September 6, 2022 Category: Neuroscience Source Type: research
Distinct volumetric features of cerebrospinal fluid distribution in idiopathic normal-pressure hydrocephalus and Alzheimer ’s disease
ConclusionsAssociations between CSF volumes suggest that there might be different mechanisms between INPH and AD to explain their respective lateral ventricular dilations. The ratio of lateral ventricle to high-convexity subarachnoid space volumes distinguishes INPH from AD with good diagnostic sensitivity and specificity. We propose to refer to this ratio as the VOSS (ventricle over subarachnoid space) index. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - September 1, 2022 Category: Neuroscience Source Type: research
Microglia-derived CCL2 has a prime role in neocortex neuroinflammation
ConclusionsThis finding supports relevant pathogenetic and clinical aspects of the human disease, while the demonstrated early control of neuroinflammation and BBB permeability exerted by treatment with MSCs may have important therapeutic implications. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - August 30, 2022 Category: Neuroscience Source Type: research
Mathematical modelling of the CSF system: effects of microstructures and posture on optic nerve subarachnoid space dynamics
ConclusionsMicrostructures affect pressure transmission along the ONSAS, potentially contributing to ONSAS compartmentalization in upright postures. Different pathways for ocular glymphatic flow were predicted for different postures. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - August 30, 2022 Category: Neuroscience Source Type: research
Membrane transporters control cerebrospinal fluid formation independently of conventional osmosis to modulate intracranial pressure
ConclusionsCSF secretion appears to not rely on conventional osmosis, but rather occur by a concerted effort of different choroidal transporters, possibly via a molecular mode of water transport inherent in the proteins themselves. Therapeutic modulation of the rate of CSF secretion may be employed as a strategy to modulate ICP. These insights identify new promising therapeutic targets against brain pathologies associated with elevated ICP. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - August 29, 2022 Category: Neuroscience Source Type: research
A transcriptomic analysis of cerebral microvessels reveals the involvement of Notch1 signaling in endothelial mitochondrial-dysfunction-dependent BBB disruption
ConclusionThese results suggest that the Notch1 signaling pathway acts as an upstream regulator of DEGs and can be a target to regulate the changes involved with endothelial mitochondrial dysfunction-dependent BBB disruption. Thus, treatment methods that activate Notch1 may be beneficial in acute brain injuries by protecting BBB integrity. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - August 26, 2022 Category: Neuroscience Source Type: research
Role of aging in Blood –Brain Barrier dysfunction and susceptibility to SARS-CoV-2 infection: impacts on neurological symptoms of COVID-19
AbstractCOVID-19, which is caused by Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), has resulted in devastating morbidity and mortality worldwide due to lethal pneumonia and respiratory distress. In addition, the central nervous system (CNS) is well documented to be a target of SARS-CoV-2, and studies detected SARS-CoV-2 in the brain and the cerebrospinal fluid of COVID-19 patients. The blood –brain barrier (BBB) was suggested to be the major route of SARS-CoV-2 infection of the brain. Functionally, the BBB is created by an interactome between endothelial cells, pericytes, astrocytes, microglia, and neuro...
Source: Fluids and Barriers of the CNS - August 18, 2022 Category: Neuroscience Source Type: research
Posthemorrhagic hydrocephalus associates with elevated inflammation and CSF hypersecretion via activation of choroidal transporters
ConclusionsCSF hypersecretion may contribute to PHH development, likely due to hyperactivity of choroid plexus transporters. The hemorrhage-induced inflammation detected in CSF and in the choroid plexus tissue may represent the underlying pathology. Therapeutic targeting of such pathways may be employed in future treatment strategies towards PHH patients. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - August 10, 2022 Category: Neuroscience Source Type: research
Antibody indices of infectious pathogens from serum and cerebrospinal fluid in patients with schizophrenia spectrum disorders
ConclusionsEvidence for the role of intrathecal EBV antibody synthesis was found in patients with chronic SSD compared to those first diagnosed. Apart from a possible infectious factor in SSD pathophysiology, the evidence for polyspecific immune response in outlier patients may also suggest the involvement of further immunological processes in a small subgroup of SSD patients. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - July 29, 2022 Category: Neuroscience Source Type: research
Extracellular vesicles through the blood –brain barrier: a review
AbstractExtracellular vesicles (EVs) are particles naturally released from cells that are delimited by a lipid bilayer and are unable to replicate. How the EVs cross the Blood –Brain barrier (BBB) in a bidirectional manner between the bloodstream and brain parenchyma remains poorly understood. Most in vitro models that have evaluated this event have relied on monolayer transwell or microfluidic organ-on-a-chip techniques that do not account for the combined effect of al l cellular layers that constitute the BBB at different sites of the Central Nervous System. There has not been direct transcytosis visualization through ...
Source: Fluids and Barriers of the CNS - July 25, 2022 Category: Neuroscience Source Type: research
Ventricular volume in relation to lumbar CSF levels of amyloid- β 1–42, tau and phosphorylated tau in iNPH, is there a dilution effect?
ConclusionsThe findings did not support a major dilution effect in iNPH, at least not in females. The only result in favor for dilution was a weak negative correlation between VV and A β42 but not with the other lumbar CSF biomarkers. The different results between males and females suggest that future investigations of the CSF pattern in iNPH would gain from sex-based subgroup analysis. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - July 17, 2022 Category: Neuroscience Source Type: research
