The brain interstitial system: Anatomy, modeling, in vivo measurement, and applications

Lei, Yiming; Han, Hongbin; Yuan, Fan; Javeed, Aqeel; Zhao, Yong

doi:10.1016/j.pneurobio.2015.12.007

Cited by 165 publications

(175 citation statements)

References 230 publications

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“…The CSF is produced by the choroid plexus (up to 80%) filling the lateral, third, and fourth ventricles, while the remaining 20% may derive from the ependymal cells lining the ventricles and from the subarachnoid space. 23 The ISF has a unique composition of ions, proteins, peptides, and neurotransmitters, essential to maintain the isotonicity of the brain cellular microenvironment. 19,21 A component of the CSF flows along the Virchow-Robin space and in the perivascular space (pia and the glia limitans).…”

Section: Box 1: Cns Fluidsmentioning

confidence: 99%

“…The ISF fills the extracellular space within the brain parenchyma (15%-20% of total brain volume). 23 The ISF has a unique composition of ions, proteins, peptides, and neurotransmitters, essential to maintain the isotonicity of the brain cellular microenvironment. 20 The ISF derives at the BBB from secretion processes, where water follows ionic transport into the brain and across the endothelium (reviewed in Brinker et al 19 ).…”

Section: Box 1: Cns Fluidsmentioning

confidence: 99%

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Central nervous system lymphatic unit, immunity, and epilepsy: Is there a link?

Noè

Marchi

2019

Epilepsia Open

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Summary The recent definition of a network of lymphatic vessels in the meninges surrounding the brain and the spinal cord has advanced our knowledge on the functional anatomy of fluid movement within the central nervous system (CNS). Meningeal lymphatic vessels along dural sinuses and main nerves contribute to cerebrospinal fluid (CSF) drainage, integrating the cerebrovascular and periventricular routes, and forming a circuit that we here define as the CNS‐lymphatic unit. The latter unit is important for parenchymal waste clearance, brain homeostasis, and the regulation of immune or inflammatory processes within the brain. Disruption of fluid drain mechanisms may promote or sustain CNS disease, conceivably applicable to epilepsy where extracellular accumulation of macromolecules and metabolic by‐products occur in the interstitial and perivascular spaces. Herein we address an emerging concept and propose a theoretical framework on: (a) how a defect of brain clearance of macromolecules could favor neuronal hyperexcitability and seizures, and (b) whether meningeal lymphatic vessel dysfunction contributes to the neuroimmune cross‐talk in epileptic pathophysiology. We propose possible molecular interventions targeting meningeal lymphatic dysfunctions, a potential target for immune‐mediated epilepsy.

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Section: Box 1: Cns Fluidsmentioning

confidence: 99%

Section: Box 1: Cns Fluidsmentioning

confidence: 99%

Central nervous system lymphatic unit, immunity, and epilepsy: Is there a link?

Noè

Marchi

2019

Epilepsia Open

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“…9, respectively. Permeability coefficient of the contact surface of brain tissue and ventricular system to sodium 10 6 (cm s −1 ) A large value was used Permeability coefficient of the contact surface of brain tissue and subarachnoid space to sodium 10 6 (cm s −1 ) A large value was used ISF/brain volume fraction 0.2 (dimensionless) [8,21] Rat brain density 1 (g cm −3 ) [8] ′ and ′ were calculated assuming that the CSF sodium level is in equilibrium with the brain tissue sodium concentration at t=0 (steady state):…”

Section: Formulation Of the Modelmentioning

confidence: 99%

Regulation of CSF and brain tissue sodium levels by the blood-CSF and blood-brain barriers during migraine

Ghaffari

Grant²,

Petzold

et al. 2019

Preprint

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BackgroundCerebrospinal fluid (CSF) and brain tissue sodium levels increase during migraine. However, little is known regarding the underlying mechanisms of sodium homeostasis disturbance in the brain during the onset and propagation of migraine. Exploring the cause of sodium dysregulation in the brain is important, since correction of the altered sodium homeostasis could potentially treat migraine. Under the hypothesis that disturbances in sodium transport mechanisms at the blood-CSF barrier (BCSFB) and/or the blood-brain barrier (BBB) are the underlying cause of the elevated CSF and brain tissue sodium levels during migraines, we developed a mechanistic, differential equation model of a rat's brain to compare the significance of the BCSFB and the BBB in controlling CSF and brain tissue sodium levels. The model includes the ventricular system, subarachnoid space, brain tissue and blood. Sodium transport from blood to CSF across the BCSFB, and from blood to brain tissue across the BBB were modeled by influx permeability coefficients and , respectively, while sodium movement from CSF into blood across the BCSFB, and from brain tissue to blood across the BBB were modeled by efflux permeability coefficients ′ and ′ , respectively. We then performed a global sensitivity analysis to investigate the sensitivity of the ventricular CSF, subarachnoid CSF and brain tissue sodium concentrations to pathophysiological variations in , , ′ and ′ . Our results show that the ventricular CSF sodium concentration is highly influenced by perturbations of , and to a much lesser extent by perturbations of ′ . Brain tissue and subarachnoid CSF sodium concentrations are more sensitive to pathophysiological variations of and ′ than variations of and ′ within 30 minutes of the onset of the perturbations. However, is the most sensitive model parameter, followed by and ′ , in controlling brain tissue and subarachnoid CSF sodium levels within 2 hours of the perturbation onset.

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“…It occupies roughly 15%-20% of total brain volume and is composed of interstitial fluid (ISF) and extracellular matrix. [9] Because the interstitial space is very narrow and tortuous, diffusion within the ISF is "hindered" with apparent diffusion coefficients being 30% to 60% lower than TCP Transl Clin Pharmacol their expected free-water values. An estimated 20% of total CSF production is generated in the interstitial space by extrachoroidal secretion and cerebral capillaries that cross the blood-brain barrier.…”

Section: Underlying Physiologymentioning

confidence: 99%

Intracerebroventricular drug administration

Atkinson

2017

Transl Clin Pharmacol

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Among the various routes of drug administration, perhaps the least studied is intracerebroventricular (ICV) administration. This route has been shown to be particularly useful in administering to the central nervous system (CNS) drugs that do not cross the blood-brain barrier readily. As such, the ICV route is a valuable option for providing therapeutic CNS drug concentrations to treat patients with CNS infectious and neoplastic diseases. This route of drug administration also has the advantage of minimizing systemic toxicity.

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The brain interstitial system: Anatomy, modeling, in vivo measurement, and applications

Cited by 165 publications

References 230 publications

Central nervous system lymphatic unit, immunity, and epilepsy: Is there a link?

Central nervous system lymphatic unit, immunity, and epilepsy: Is there a link?

Regulation of CSF and brain tissue sodium levels by the blood-CSF and blood-brain barriers during migraine

Intracerebroventricular drug administration

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