Tightness of the blood-brain barrier and evidence for brain interstitial fluid flow in the cuttlefish, Sepia officinalis.

L-glutamine (Gln) is the most abundant amino acid in plasma and cerebrospinal fluid and a precursor for the main central nervous system excitatory (L-glutamate) and inhibitory (γ-aminobutyric acid (GABA)) neurotransmitters. Concentrations of Gln and 13 other brain interstitial fluid amino acids were measured in awake, freely moving mice by hippocampal microdialysis using an extrapolation to zero flow rate method. Interstitial fluid levels for all amino acids including Gln were ∼5–10 times lower than in cerebrospinal fluid. Although the large increase in plasma Gln by intraperitoneal (IP) injection of 15N2-labeled Gln (hGln) did not increase total interstitial fluid Gln, low levels of hGln were detected in microdialysis samples. Competitive inhibition of system A (SLC38A1&2; SNAT1&2) or system L (SLC7A5&8; LAT1&2) transporters in brain by perfusion with α-(methylamino)-isobutyric acid (MeAIB) or 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) respectively, was tested. The data showed a significantly greater increase in interstitial fluid Gln upon BCH than MeAIB treatment. Furthermore, brain BCH perfusion also strongly increased the influx of hGln into interstitial fluid following IP injection consistent with transstimulation of LAT1-mediated transendothelial transport. Taken together, the data support the independent homeostatic regulation of amino acids in interstitial fluid vs. cerebrospinal fluid and the role of the blood–brain barrier expressed SLC7A5/LAT1 as a key interstitial fluid gatekeeper.

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Insulin transport into the brain

AJP Cell Physiology ◽

10.1152/ajpcell.00240.2017 ◽

2018 ◽

Vol 315 (2) ◽

pp. C125-C136 ◽

Cited By ~ 7

Author(s):

Sarah M. Gray ◽

Eugene J. Barrett

Keyword(s):

Blood Brain Barrier ◽

Interstitial Fluid ◽

Brain Barrier ◽

Status Report ◽

Amyloid Peptides ◽

Brain Interstitial Fluid ◽

Insulin Transport ◽

Blood Brain ◽

Brain Insulin ◽

The Brain

While there is a growing consensus that insulin has diverse and important regulatory actions on the brain, seemingly important aspects of brain insulin physiology are poorly understood. Examples include: what is the insulin concentration within brain interstitial fluid under normal physiologic conditions; whether insulin is made in the brain and acts locally; does insulin from the circulation cross the blood-brain barrier or the blood-CSF barrier in a fashion that facilitates its signaling in brain; is insulin degraded within the brain; do privileged areas with a “leaky” blood-brain barrier serve as signaling nodes for transmitting peripheral insulin signaling; does insulin action in the brain include regulation of amyloid peptides; whether insulin resistance is a cause or consequence of processes involved in cognitive decline. Heretofore, nearly all of the studies examining brain insulin physiology have employed techniques and methodologies that do not appreciate the complex fluid compartmentation and flow throughout the brain. This review attempts to provide a status report on historical and recent work that begins to address some of these issues. It is undertaken in an effort to suggest a framework for studies going forward. Such studies are inevitably influenced by recent physiologic and genetic studies of insulin accessing and acting in brain, discoveries relating to brain fluid dynamics and the interplay of cerebrospinal fluid, brain interstitial fluid, and brain lymphatics, and advances in clinical neuroimaging that underscore the dynamic role of neurovascular coupling.

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Slowly Changing Bioelectric Potentials Associated With the Blood-Brain Barrier

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1958.195.1.7 ◽

1958 ◽

Vol 195 (1) ◽

pp. 7-22 ◽

Cited By ~ 86

Author(s):

Robert D. Tschirgi ◽

J. Langdon Taylor

Keyword(s):

Cerebral Cortex ◽

Blood Brain Barrier ◽

Interstitial Fluid ◽

Brain Barrier ◽

Membrane Diffusion ◽

Arterial Blood ◽

Blood Ph ◽

Blood Brain ◽

The Central Nervous System ◽

Bioelectric Potentials

A slowly changing bioelectric potential difference (P.D.) is measured in rats, rabbits, cats and dogs between various regions of the central nervous system (CNS) and the blood within the jugular vein. It is shown that the CNS-blood P.D. is very sensitive to alterations in alveolar CO2 tension, but this relationship is dependent upon the H+ concentration rather than CO2 per se. Whereas increasing intravenous H+ concentration increases CNS positivity, topical application of acid solutions directly to the cerebral cortex decreases CNS positivity. The same relationship is found for intravenous and topical K+. Anoxia and circulatory failure produce CNS negative deflections, often exceeding 15 mv, which do not return to zero for over 24 hours after death. Simultaneous measurements of arterial blood pH, cerebral cortex pH and CNS-blood P.D. reveal the following relationship among these variables: ΔP.D. = κ Δ log10 [H+]a/[H+]i where [H+]a is the H+ concentration of the arterial blood and [H+]i is the H+ concentration of the CNS interstitial fluid. For the CNS-blood P.D. between cerebral cortex and jugular blood of rabbits and rats, κ is found to be 29 ± 5. These results are interpreted as indicating a source of emf across the pan-vascular blood-brain barrier which resembles a membrane diffusion potential. The blood-brain barrier is postulated to be more permeable to H+ and K+ than to anions and other cations.

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Autoradiographic Patterns of Brain Interstitial Fluid Flow After Collagenase-induced Haemorrhage in Rat

Brain Edema VIII ◽

10.1007/978-3-7091-9115-6_95 ◽

1990 ◽

pp. 280-282

Author(s):

G. A. Rosenberg ◽

E. Estrada ◽

M. Wesley ◽

W. T. Kyner

Keyword(s):

Fluid Flow ◽

Interstitial Fluid ◽

Interstitial Fluid Flow ◽

Brain Interstitial Fluid

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Fluid Flow-Trypanosome Interaction at the Blood Brain Barrier

Journal of Surgical Research ◽

10.1016/j.jss.2013.11.1075 ◽

2014 ◽

Vol 186 (2) ◽

pp. 692

Author(s):

B.J. Sumpio ◽

D. Grab ◽

G. Chitragari ◽

S. Shalby ◽

B.E. Sumpio

Keyword(s):

Fluid Flow ◽

Blood Brain Barrier ◽

Brain Barrier ◽

Blood Brain

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Acanthamoeba interactions with the blood–brain barrier under dynamic fluid flow

Experimental Parasitology ◽

10.1016/j.exppara.2012.08.012 ◽

2012 ◽

Vol 132 (3) ◽

pp. 367-372 ◽

Cited By ~ 2

Author(s):

James Edwards-Smallbone ◽

Richard J. Pleass ◽

Naveed A. Khan ◽

Robin J. Flynn

Keyword(s):

Fluid Flow ◽

Blood Brain Barrier ◽

Brain Barrier ◽

Blood Brain

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Flow induces barrier and glycocalyx-related genes and negative surface charge in a lab-on-a-chip human blood-brain barrier model

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x21992638 ◽

2021 ◽

pp. 0271678X2199263

Author(s):

Ana R Santa-Maria ◽

Fruzsina R Walter ◽

Ricardo Figueiredo ◽

András Kincses ◽

Judit P Vigh ◽

...

Keyword(s):

Endothelial Cells ◽

Fluid Flow ◽

Surface Charge ◽

Blood Brain Barrier ◽

Lab On A Chip ◽

Brain Barrier ◽

Dynamic Conditions ◽

Blood Brain ◽

Negative Surface ◽

Negative Surface Charge

Microfluidic lab-on-a-chip (LOC) devices allow the study of blood-brain barrier (BBB) properties in dynamic conditions. We studied a BBB model, consisting of human endothelial cells derived from hematopoietic stem cells in co-culture with brain pericytes, in an LOC device to study fluid flow in the regulation of endothelial, BBB and glycocalyx-related genes and surface charge. The highly negatively charged endothelial surface glycocalyx functions as mechano-sensor detecting shear forces generated by blood flow on the luminal side of brain endothelial cells and contributes to the physical barrier of the BBB. Despite the importance of glycocalyx in the regulation of BBB permeability in physiological conditions and in diseases, the underlying mechanisms remained unclear. The MACE-seq gene expression profiling analysis showed differentially expressed endothelial, BBB and glycocalyx core protein genes after fluid flow, as well as enriched pathways for the extracellular matrix molecules. We observed increased barrier properties, a higher intensity glycocalyx staining and a more negative surface charge of human brain-like endothelial cells (BLECs) in dynamic conditions. Our work is the first study to provide data on BBB properties and glycocalyx of BLECs in an LOC device under dynamic conditions and confirms the importance of fluid flow for BBB culture models.

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