scholarly journals CrossTalk proposal: The glymphatic system supports convective exchange of cerebrospinal fluid and brain interstitial fluid that is mediated by perivascular aquaporin‐4

2019 ◽  
Vol 597 (17) ◽  
pp. 4417-4419 ◽  
Author(s):  
Jeffrey Iliff ◽  
Matthew Simon
Keyword(s):  
Cerebrospinal Fluid ◽  
Interstitial Fluid ◽  
Aquaporin 4 ◽  
Glymphatic System ◽  
Brain Interstitial Fluid ◽  
Convective Exchange

scholarly journals Impairment of the glymphatic system after diabetes

2016 ◽  
Vol 37 (4) ◽  
pp. 1326-1337 ◽  
Author(s):  
Quan Jiang ◽  
Li Zhang ◽  
Guangliang Ding ◽  
Esmaeil Davoodi-Bojd ◽  
Qingjiang Li ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cerebrospinal Fluid ◽  
Type 2 Diabetes Mellitus ◽  
Cognitive Deficits ◽  
Interstitial Fluid ◽  
Brain Mri ◽  
Fluid Exchange ◽  
Glymphatic System

The glymphatic system has recently been shown to clear brain extracellular solutes and abnormalities in glymphatic clearance system may contribute to both initiation and progression of neurological diseases. Despite that diabetes is known as a risk factor for vascular diseases, little is known how diabetes affects the glymphatic system. The current study is the first investigation of the effect of diabetes on the glymphatic system and the link between alteration of glymphatic clearance and cognitive impairment in Type-2 diabetes mellitus rats. MRI analysis revealed that clearance of cerebrospinal fluid contrast agent Gd-DTPA from the interstitial space was slowed by a factor of three in the hippocampus of Type-2 diabetes mellitus rats compared to the non-DM rats and confirmed by florescence imaging analysis. Cognitive deficits detected by behavioral tests were highly and inversely correlated to the retention of Gd-DTPA contrast and fluorescent tracer in the hippocampus of Type-2 diabetes mellitus rats. Type-2 diabetes mellitus suppresses clearance of interstitial fluid in the hippocampus and hypothalamus, suggesting that an impairment of the glymphatic system contributes to Type-2 diabetes mellitus-induced cognitive deficits. Whole brain MRI provides a sensitive, non-invasive tool to quantitatively evaluate cerebrospinal fluid and interstitial fluid exchange in Type-2 diabetes mellitus and possibly in other neurological disorders, with potential clinical application.

scholarly journals The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans

Science ◽  
2019 ◽  
Vol 363 (6429) ◽  
pp. 880-884 ◽  
Author(s):  
Jerrah K. Holth ◽  
Sarah K. Fritschi ◽  
Chanung Wang ◽  
Nigel P. Pedersen ◽  
John R. Cirrito ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Sleep Deprivation ◽  
Interstitial Fluid ◽  
Tau Pathology ◽  
Brain Interstitial Fluid ◽  
Spreading Model ◽  
Csf Levels ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Chronic Sleep

The sleep-wake cycle regulates interstitial fluid (ISF) and cerebrospinal fluid (CSF) levels of β-amyloid (Aβ) that accumulates in Alzheimer’s disease (AD). Furthermore, chronic sleep deprivation (SD) increases Aβ plaques. However, tau, not Aβ, accumulation appears to drive AD neurodegeneration. We tested whether ISF/CSF tau and tau seeding and spreading were influenced by the sleep-wake cycle and SD. Mouse ISF tau was increased ~90% during normal wakefulness versus sleep and ~100% during SD. Human CSF tau also increased more than 50% during SD. In a tau seeding-and-spreading model, chronic SD increased tau pathology spreading. Chemogenetically driven wakefulness in mice also significantly increased both ISF Aβ and tau. Thus, the sleep-wake cycle regulates ISF tau, and SD increases ISF and CSF tau as well as tau pathology spreading.

scholarly journals Fluid Dynamics Inside the Brain Barrier: Current Concept of Interstitial Flow, Glymphatic Flow, and Cerebrospinal Fluid Circulation in the Brain

2018 ◽  
Vol 25 (2) ◽  
pp. 155-166 ◽  
Author(s):  
Tsutomu Nakada ◽  
Ingrid L. Kwee
Keyword(s):  
Fluid Dynamics ◽  
Cerebrospinal Fluid ◽  
Interstitial Fluid ◽  
Systemic Circulation ◽  
Free Access ◽  
Alternative Mechanism ◽  
Interstitial Flow ◽  
Fluid Circulation ◽  
Brain Interstitial Fluid ◽  
The Brain

The discovery of the water specific channel, aquaporin, and abundant expression of its isoform, aquaporin-4 (AQP-4), on astrocyte endfeet brought about significant advancements in the understanding of brain fluid dynamics. The brain is protected by barriers preventing free access of systemic fluid. The same barrier system, however, also isolates brain interstitial fluid from the hydro-dynamic effect of the systemic circulation. The systolic force of the heart, an essential factor for proper systemic interstitial fluid circulation, cannot be propagated to the interstitial fluid compartment of the brain. Without a proper alternative mechanism, brain interstitial fluid would stay stagnant. Water influx into the peri-capillary Virchow-Robin space (VRS) through the astrocyte AQP-4 system compensates for this hydrodynamic shortage essential for interstitial flow, introducing the condition virtually identical to systemic circulation, which by virtue of its fenestrated capillaries creates appropriate interstitial fluid motion. Interstitial flow in peri-arterial VRS constitutes an essential part of the clearance system for β-amyloid, whereas interstitial flow in peri-venous VRS creates bulk interstitial fluid flow, which, together with the choroid plexus, creates the necessary ventricular cerebrospinal fluid (CSF) volume for proper CSF circulation.

scholarly journals Brain interstitial fluid glutamine homeostasis is controlled by blood–brain barrier SLC7A5/LAT1 amino acid transporter

2016 ◽  
Vol 36 (11) ◽  
pp. 1929-1941 ◽  
Author(s):  
Elena Dolgodilina ◽  
Stefan Imobersteg ◽  
Endre Laczko ◽  
Tobias Welt ◽  
Francois Verrey ◽  
...  
Keyword(s):  
Amino Acids ◽  
Cerebrospinal Fluid ◽  
Amino Acid ◽  
Blood Brain Barrier ◽  
Interstitial Fluid ◽  
Competitive Inhibition ◽  
Brain Barrier ◽  
Brain Interstitial Fluid ◽  
Blood Brain ◽  
System L

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.

Fisiopatología de la hidrocefália idiopática de presión normal (parte 3): sistemaa glinfático

2016 ◽  
Vol 21 (2) ◽  
pp. 28-37
Author(s):  
Oscar Solís-Salgado ◽  
José Luis López-Payares ◽  
Mauricio Ayala-González
Keyword(s):  
Amyloid Beta ◽  
Interstitial Fluid ◽  
Amyloid Β ◽  
Bulk Flow ◽  
Polyethylene Glycols ◽  
Brain Interstitial Fluid ◽  
El Sistema ◽  
Arterial Pulsation ◽  
The Brain

Las vías de drenaje solutos del sistema nervioso central (SNC) participan en el recambio de liquido intersticial con el líquido cefalorraquídeo (LIT-LCR), generando un estado de homeostasis. Las alteraciones dentro de este sistema homeostático afectará la eliminación de solutos del espacio intersticial (EIT) como el péptido βa y proteína tau, los cuales son sustancias neurotóxicas para el SNC. Se han utilizado técnicas experimentales para poder analizar el intercambio LIT-LCR, las cuales revelan que este intercambio tiene una estructura bien organizada. La eliminación de solutos del SNC no tiene una estructura anatómica propiamente, se han descubierto vías de eliminación de solutos a través de marcadores florecentes en el espacio subaracnoideo, cisternas de la base y sistema ventricular que nos permiten observar una serie de vías ampliamente distribuidas en el cerebro. El LCR muestra que tiene una función linfática debido a su recambio con el LIT a lo largo de rutas paravasculares. Estos espacios que rodean la superficie arterial así como los espacios de Virchow-Robin y el pie astrocitico junto con la AQP-4, facilitan la entrada de LCR para-arterial y el aclaramiento de LIT para-venoso dentro del cerebro. El flujo y dirección que toma el LCR por estas estructuras, es conducido por la pulsación arterial. Esta función será la que finalmente llevara a la eliminación de estas sustancias neurotóxicas. En base a la dependencia de este flujo para la eliminación de sustancias se propone que el sistema sea llamado “ la Vía Glinfática”. La bibliografía así como las limitaciones que se encuentran en esta revisión están dadas por la metodología de búsqueda que ha sido realizada principalmente en PubMed utilizando los siguientes términos Mesh: Cerebral Arterial Pulsation, the brain via paravascular, drainage of amyloid-beta, bulk flow of brain interstitial fluid, radiolabeled polyethylene glycols and albumin, amyloid-β, the perivascular astroglial sheath, Brain Glymphatic Transport.

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