7 results on '"Bulk flow"'
Search Results
2. Is bulk flow plausible in perivascular, paravascular and paravenous channels?
- Author
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Faghih MM and Sharp MK
- Subjects
- Basement Membrane metabolism, Brain blood supply, Brain metabolism, Humans, Viscosity, Blood Vessels metabolism, Cerebrospinal Fluid metabolism, Extracellular Fluid metabolism, Models, Biological
- Abstract
Background: Transport of solutes has been observed in the spaces surrounding cerebral arteries and veins. Indeed, transport has been found in opposite directions in two different spaces around arteries. These findings have motivated hypotheses of bulk flow within these spaces. The glymphatic circulation hypothesis involves flow of cerebrospinal fluid from the cortical subarachnoid space to the parenchyma along the paraarterial (extramural, Virchow-Robin) space around arteries, and return flow to the cerebrospinal fluid (CSF) space via paravenous channels. The second hypothesis involves flow of interstitial fluid from the parenchyma to lymphatic vessels along basement membranes between arterial smooth muscle cells., Methods: This article evaluates the plausibility of steady, pressure-driven flow in these channels with one-dimensional branching models., Results: According to the models, the hydraulic resistance of arterial basement membranes is too large to accommodate estimated interstitial perfusion of the brain, unless the flow empties to lymphatic ducts after only several generations (still within the parenchyma). The estimated pressure drops required to drive paraarterial and paravenous flows of the same magnitude are not large, but paravenous flow back to the CSF space means that the total pressure difference driving both flows is limited to local pressure differences among the different CSF compartments, which are estimated to be small., Conclusions: Periarterial flow and glymphatic circulation driven by steady pressure are both found to be implausible, given current estimates of anatomical and fluid dynamic parameters.
- Published
- 2018
- Full Text
- View/download PDF
3. Interactions of brain, blood, and CSF: a novel mathematical model of cerebral edema.
- Author
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Doron, Omer, Zadka, Yuliya, Barnea, Ofer, and Rosenthal, Guy
- Subjects
- *
CEREBRAL edema , *FLUID injection , *CEREBRAL circulation , *EXTRACELLULAR fluid , *INTRACRANIAL pressure - Abstract
Background: Previous models of intracranial pressure (ICP) dynamics have not included flow of cerebral interstitial fluid (ISF) and changes in resistance to its flow when brain swelling occurs. We sought to develop a mathematical model that incorporates resistance to the bulk flow of cerebral ISF to better simulate the physiological changes that occur in pathologies in which brain swelling predominates and to assess the model's ability to depict changes in cerebral physiology associated with cerebral edema. Methods: We developed a lumped parameter model which includes a representation of cerebral ISF flow within brain tissue and its interactions with CSF flow and cerebral blood flow (CBF). The model is based on an electrical analog circuit with four intracranial compartments: the (1) subarachnoid space, (2) brain, (3) ventricles, (4) cerebral vasculature and the extracranial spinal thecal sac. We determined changes in pressure and volume within cerebral compartments at steady-state and simulated physiological perturbations including rapid injection of fluid into the intracranial space, hyperventilation, and hypoventilation. We simulated changes in resistance to flow or absorption of CSF and cerebral ISF to model hydrocephalus, cerebral edema, and to simulate disruption of the blood–brain barrier (BBB). Results: The model accurately replicates well-accepted features of intracranial physiology including the exponential-like pressure–volume curve with rapid fluid injection, increased ICP pulse pressure with rising ICP, hydrocephalus resulting from increased resistance to CSF outflow, and changes associated with hyperventilation and hypoventilation. Importantly, modeling cerebral edema with increased resistance to cerebral ISF flow mimics key features of brain swelling including elevated ICP, increased brain volume, markedly reduced ventricular volume, and a contracted subarachnoid space. Similarly, a decreased resistance to flow of fluid across the BBB leads to an exponential-like rise in ICP and ventricular collapse. Conclusions: The model accurately depicts the complex interactions that occur between pressure, volume, and resistances to flow in the different intracranial compartments under specific pathophysiological conditions. In modelling resistance to bulk flow of cerebral ISF, it may serve as a platform for improved modelling of cerebral edema and blood–brain barrier disruption that occur following brain injury. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
4. Tissue Barriers : Diffusion, Bulk Flow, and Volume Transmission of Proteins and Peptides within the Brain
- Author
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Johanson, Conrad E., Borchardt, Ronald T., editor, Audus, Kenneth L., editor, and Raub, Thomas J., editor
- Published
- 1993
- Full Text
- View/download PDF
5. Is bulk flow plausible in perivascular, paravascular and paravenous channels?
- Author
-
Mohammad M. Faghih and M. Keith Sharp
- Subjects
0301 basic medicine ,Cerebral arteries ,Models, Biological ,Basement Membrane ,lcsh:RC346-429 ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Cerebrospinal fluid ,Developmental Neuroscience ,Interstitial fluid ,Parenchyma ,medicine ,Humans ,Paravenous flow ,lcsh:Neurology. Diseases of the nervous system ,Cerebrospinal Fluid ,Paravascular flow ,Bulk flow ,Viscosity ,Research ,Perivascular flow ,Brain ,Extracellular Fluid ,Brain clearance system ,General Medicine ,Anatomy ,030104 developmental biology ,medicine.anatomical_structure ,Neurology ,Flow (mathematics) ,Blood Vessels ,Glymphatic system ,Subarachnoid space ,Current (fluid) ,030217 neurology & neurosurgery ,Geology - Abstract
Background Transport of solutes has been observed in the spaces surrounding cerebral arteries and veins. Indeed, transport has been found in opposite directions in two different spaces around arteries. These findings have motivated hypotheses of bulk flow within these spaces. The glymphatic circulation hypothesis involves flow of cerebrospinal fluid from the cortical subarachnoid space to the parenchyma along the paraarterial (extramural, Virchow–Robin) space around arteries, and return flow to the cerebrospinal fluid (CSF) space via paravenous channels. The second hypothesis involves flow of interstitial fluid from the parenchyma to lymphatic vessels along basement membranes between arterial smooth muscle cells. Methods This article evaluates the plausibility of steady, pressure-driven flow in these channels with one-dimensional branching models. Results According to the models, the hydraulic resistance of arterial basement membranes is too large to accommodate estimated interstitial perfusion of the brain, unless the flow empties to lymphatic ducts after only several generations (still within the parenchyma). The estimated pressure drops required to drive paraarterial and paravenous flows of the same magnitude are not large, but paravenous flow back to the CSF space means that the total pressure difference driving both flows is limited to local pressure differences among the different CSF compartments, which are estimated to be small. Conclusions Periarterial flow and glymphatic circulation driven by steady pressure are both found to be implausible, given current estimates of anatomical and fluid dynamic parameters.
- Published
- 2018
6. A Generic Multi-Compartmental CNS Distribution Model Structure for 9 Drugs Allows Prediction of Human Brain Target Site Concentrations
- Author
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Willem van den Brink, Yin Cheong Wong, Meindert Danhof, Pyry A. J. Välitalo, Johannes H. Proost, Dymphy Huntjens, An Vermeulen, Elizabeth C. M. de Lange, William Couet, Walter Krauwinkel, Claire Dahyot-Fizelier, Dirk-Jan van den Berg, Robin Hartman, Vincent Aranzana-Climent, Sandrine Marchand, Suruchi Bakshi, Yumi Yamamoto, Johan G. C. van Hasselt, Biopharmaceuticals, Discovery, Design and Delivery (BDDD), Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Center for Liver, Digestive and Metabolic Diseases (CLDM), Nanomedicine & Drug Targeting, National cerebral and cardiovascular center research institute, Leiden University, Janssen Pharmaceutica [Beerse], University of Groningen [Groningen], Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, and Leiden Amsterdam Center for Drug Research (LACDR)
- Subjects
Male ,CISTERNA-MAGNA ,[SDV]Life Sciences [q-bio] ,Pharmaceutical Science ,Pharmacology ,030226 pharmacology & pharmacy ,0302 clinical medicine ,Cerebrospinal fluid ,BARRIER PERMEABILITY ,Extracellular fluid ,Pharmacology (medical) ,Tissue Distribution ,ComputingMilieux_MISCELLANEOUS ,media_common ,Morphine ,Brain ,P-GLYCOPROTEIN ,Human brain ,[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences ,3. Good health ,medicine.anatomical_structure ,Target site ,Molecular Medicine ,human prediction ,pharmacokinetics ,Biotechnology ,Research Paper ,Drug ,media_common.quotation_subject ,Central nervous system ,BULK FLOW ,Computational biology ,Biology ,Blood–brain barrier ,RAT-BRAIN ,Models, Biological ,03 medical and health sciences ,central nervous system (CNS) ,PHARMACOKINETIC MODEL ,Pharmacokinetics ,translational model ,medicine ,Animals ,Humans ,Rats, Wistar ,Acetaminophen ,PLASMA-PROTEIN BINDING ,Organic Chemistry ,CENTRAL-NERVOUS-SYSTEM ,CEREBROSPINAL-FLUID SYSTEM ,Models, Theoretical ,blood-brain barrier ,Rats ,CHOROID-PLEXUS ,030217 neurology & neurosurgery - Abstract
Purpose Predicting target site drug concentration in the brain is of key importance for the successful development of drugs acting on the central nervous system. We propose a generic mathematical model to describe the pharmacokinetics in brain compartments, and apply this model to predict human brain disposition. Methods A mathematical model consisting of several physiological brain compartments in the rat was developed using rich concentration-time profiles from nine structurally diverse drugs in plasma, brain extracellular fluid, and two cerebrospinal fluid compartments. The effect of active drug transporters was also accounted for. Subsequently, the model was translated to predict human concentration-time profiles for acetaminophen and morphine, by scaling or replacing system- and drug-specific parameters in the model. Results A common model structure was identified that adequately described the rat pharmacokinetic profiles for each of the nine drugs across brain compartments, with good precision of structural model parameters (relative standard error
- Published
- 2017
7. Rebuttal from Matthew Simon and Jeffrey Iliff.
- Author
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Simon, Matthew and Iliff, Jeffrey
- Subjects
- *
CEREBROSPINAL fluid , *BRAIN anatomy , *EXTRACELLULAR fluid - Abstract
Several studies have demonstrated size-independent solute efflux from brain tissue, reflecting a bulk flow-dependent process (Cserr I et al i . Careful anatomical studies defined routes of interstitial solute efflux to the CSF and the cervical lymphatic drainage (Louveau I et al i . A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid beta. [Extracted from the article]
- Published
- 2019
- Full Text
- View/download PDF
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