Oxygen glucose deprivation-pretreated astrocyte-derived exosomes attenuates intracerebral hemorrhage (ICH)-induced BBB disruption through miR-27a-3p /ARHGAP25/Wnt/ β-catenin axis
ConclusionTaken together, these findings firstly revealed that miR-27a-3p, as one of the main components of OGD-pretreated ADEVs, attenuated BBB destruction and improved neurological deficits following ICH by regulating endothelial ARHGAP25/Wnt/ β-catenin axis. OGD-ADEVs might be a novel strategy for the treatment of ICH.this study implicates that EVs from OGD pre-stimulated astrocytes.Graphical Abstract (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - January 19, 2024 Category: Neuroscience Source Type: research
Hydraulic resistance of three-dimensional pial perivascular spaces in the brain
ConclusionsNeglecting off-axis velocity components underestimates the average resistance, but the error can be reduced with a simple correction factor. These results could increase the accuracy of future models of brain-wide and local CSF flow, enabling better prediction of clearance, for example, as it varies with age, brain state, and pathological conditions. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - January 11, 2024 Category: Neuroscience Source Type: research
Comparative analysis of hippocampal extracellular space uncovers widely altered peptidome upon epileptic seizure in urethane-anaesthetized rats
ConclusionsWe have detected several consequences of epileptic seizures at the peptidomic level, as altered peptide abundances of proteins that regulate epilepsy-related cellular processes. Thus, our results indicate that analyzing brain ECF by in vivo microdialysis and omics techniques is useful for monitoring brain processes, and it can be an alternative method in the discovery and analysis of CNS disease markers besides peripheral fluid analysis. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - January 11, 2024 Category: Neuroscience Source Type: research
Cocaine regulates antiretroviral therapy CNS access through pregnane-x receptor-mediated drug transporter and metabolizing enzyme modulation at the blood brain barrier
ConclusionOur findings indicate that additional considerations are needed in CNS HIV treatment strategies for people who use cocaine, as it may limit ART efficacy through regulation of drug transport and metabolizing pathways at the BBB. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - January 10, 2024 Category: Neuroscience Source Type: research
Postnatal meningeal CSF transport is primarily mediated by the arachnoid and pia maters and is not altered after intraventricular hemorrhage-posthemorrhagic hydrocephalus
ConclusionsDifferential CSF tracer handling by the meninges suggests that there are distinct roles for CSF handling between the arachnoid-pia and dura maters in the developing brain. Similarly, differences in apical vs. luminal choroid plexus CSF handling may provide insight into particle-size dependent CSF transport at the CSF-choroid plexus border. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - January 8, 2024 Category: Neuroscience Source Type: research
Blood –brain borders: a proposal to address limitations of historical blood–brain barrier terminology
AbstractMany neuroscientists use the term Blood –Brain Barrier (BBB) to emphasize restrictiveness, often equating or reducing the notion of BBB properties to tight junction molecules physically sealing cerebral endothelial cells, rather than pointing out the complexity of this biological interface with respect to its selectivity and variety of exchange between the general blood circulation and the central nervous tissue. Several authors in the field find it unfortunate that the exquisitely dynamic interfaces between blood and brain continue to be viewed primarily as obstructive barriers to transport. Although the term bl...
Source: Fluids and Barriers of the CNS - January 5, 2024 Category: Neuroscience Source Type: research
Sex, hormones and cerebrovascular function: from development to disorder
AbstractProper cerebrovascular development and neurogliovascular unit assembly are essential for brain growth and function throughout life, ensuring the continuous supply of nutrients and oxygen. This involves crucial events during pre- and postnatal stages through key pathways, including vascular endothelial growth factor (VEGF) and Wnt signaling. These pathways are pivotal for brain vascular growth, expansion, and blood –brain barrier (BBB) maturation. Interestingly, during fetal and neonatal life, cerebrovascular formation coincides with the early peak activity of the hypothalamic-pituitary-gonadal axis, supporting th...
Source: Fluids and Barriers of the CNS - January 4, 2024 Category: Neuroscience Source Type: research
Large molecules from the cerebrospinal fluid enter the optic nerve but not the retina of mice
AbstractIt has been proposed that cerebrospinal fluid (CSF) can enter and leave the retina and optic nerve along perivascular spaces surrounding the central retinal vessels as part of an aquaporin-4 (AQP4) dependent ocular ‘glymphatic’ system. Here, we injected fluorescent dextrans and antibodies into the CSF of mice at the cisterna magna and measured their distribution in the optic nerve and retina. We found that uptake of dextrans in the perivascular spaces and parenchyma of the optic nerve is highly sensitive t o the cisternal injection rate, where high injection rates, in which dextran disperses fully in the sub-ar...
Source: Fluids and Barriers of the CNS - January 4, 2024 Category: Neuroscience Source Type: research
Imaging the neurovascular unit in health and neurodegeneration: a scoping review of interdependencies between MRI measures
AbstractThe neurovascular unit (NVU) is a complex structure that facilitates nutrient delivery and metabolic waste clearance, forms the blood –brain barrier (BBB), and supports fluid homeostasis in the brain. The integrity of NVU subcomponents can be measured in vivo using magnetic resonance imaging (MRI), including quantification of enlarged perivascular spaces (ePVS), BBB permeability, cerebral perfusion and extracellular free water. The breakdown of NVU subparts is individually associated with aging, pathology, and cognition. However, how these subcomponents interact as a system, and how interdependencies are impacted...
Source: Fluids and Barriers of the CNS - December 21, 2023 Category: Neuroscience Source Type: research
Cerebral microvascular endothelial cell-derived extracellular vesicles regulate blood − brain barrier function
In conclusion, our study highligh ts the distinct and opposing effects of BBB-EV subpopulations on the BBB, both in vitro and in vivo. These findings underscore the need for further investigation into the diagnostic and therapeutic potential of BBB-EV in the context of MS. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - December 19, 2023 Category: Neuroscience Source Type: research
Characterization of an iPSC-based barrier model for blood-brain barrier investigations using the SBAD0201 stem cell line
ConclusionsIn conclusion, the novel SBAD0201-derived BBB model formed tight monolayers and was proven useful for studies investigating GLUT-1, LAT-1, and LRP-1 mediated transport across the BBB. However, the model did not express functional P-gp and thus is not suitable for the performance of drug efflux P-gp reletated studies. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - December 19, 2023 Category: Neuroscience Source Type: research
Methodological and analytical considerations for intra-operative microdialysis
ConclusionsIntra-operative HMW microdialysis can feasibly be utilized to sample the live human CNS microenvironment, including both metabolites and drugs, within one surgery. Certain variables, such as perfusate type, must be considered during and after analysis.Trial registration NCT04047264 (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - December 19, 2023 Category: Neuroscience Source Type: research
Structural characterization of SLYM —a 4th meningeal membrane
AbstractTraditionally, the meninges are described as 3 distinct layers, dura, arachnoid and pia. Yet, the classification of the connective meningeal membranes surrounding the brain is based on postmortem macroscopic examination. Ultrastructural and single cell transcriptome analyses have documented that the 3 meningeal layers can be subdivided into several distinct layers based on cellular characteristics. We here re-examined the existence of a 4th meningeal membrane, Subarachnoid Lymphatic-like Membrane or SLYM in Prox1-eGFP reporter mice. Imaging of freshly resected whole brains showed that SLYM covers the entire brain a...
Source: Fluids and Barriers of the CNS - December 14, 2023 Category: Neuroscience Source Type: research
miRNA-ome plasma analysis unveils changes in blood –brain barrier integrity associated with acute liver failure in rats
ConclusionThis work identified, to our knowledge for the first time, potential functional links between alterations in miRs residing in brain endothelium and BBB dysfunction in ALF. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - December 8, 2023 Category: Neuroscience Source Type: research
Identifying molecular tags selectively retained on the surface of brain endothelial cells to generate artificial targets for therapy delivery
AbstractCurrent strategies to identify ligands for brain delivery select candidates based on preferential binding to cell-membrane components (CMC) on brain endothelial cells (EC). However, such strategies generate ligands with inherent brain specificity limitations, as the CMC (e.g., the transferrin receptor TfR1) are also significantly expressed on peripheral EC. Therefore, novel strategies are required to identify molecules allowing increased specificity of therapy brain delivery. Here, we demonstrate that, while individual CMC are shared between brain EC and peripheral EC, their endocytic internalization rate is marked...
Source: Fluids and Barriers of the CNS - December 6, 2023 Category: Neuroscience Source Type: research
