Die Feinstruktur des molekularen Rindengraues und ihre physiologische Bedeutung

Horstmann, Ernst; Meves, H.

doi:10.1007/bf00338866

Cited by 201 publications

(36 citation statements)

References 97 publications

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“…Electron microscopy studies focused on neuropil ultrastructure have long indicated a brain ECS width of approximately 10-20 nm [21,75,81,136] and, importantly, that these narrow spaces could be accessed with tracers such as HRP (40 kDa) following intracerebroventricular injection [20,21].…”

Section: Diffusion or Flow Of The Isf In The Brain Ecs?mentioning

confidence: 99%

The role of brain barriers in fluid movement in the CNS: is there a ‘glymphatic’ system?

et al. 2018

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Brain fluids are rigidly regulated to provide stable environments for neuronal function, e.g., low K + , Ca 2+ , and protein to optimise signalling and minimise neurotoxicity. At the same time, neuronal and astroglial waste must be promptly removed. The interstitial fluid (ISF) of the brain tissue and the cerebrospinal fluid (CSF) bathing the CNS are integral to this homeostasis and the idea of a glia-lymph or 'glymphatic' system for waste clearance from brain has developed over the last 5 years. This links bulk (convective) flow of CSF into brain along the outside of penetrating arteries, glia-mediated convective transport of fluid and solutes through the brain extracellular space (ECS) involving the aquaporin-4 (AQP4) water channel, and finally delivery of fluid to venules for clearance along peri-venous spaces. However, recent evidence favours important amendments to the 'glymphatic' hypothesis, particularly concerning the role of glia and transfer of solutes within the ECS. This review discusses studies which question the role of AQP4 in ISF flow and the lack of evidence for its ability to transport solutes; summarizes attributes of brain ECS that strongly favour the diffusion of small and large molecules without ISF flow; discusses work on hydraulic conductivity and the nature of the extracellular matrix which may impede fluid movement; and reconsiders the roles of the perivascular space (PVS) in CSF-ISF exchange and drainage. We also consider the extent to which CSF-ISF exchange is possible and desirable, the impact of neuropathology on fluid drainage, and why using CSF as a proxy measure of brain components or drug delivery is problematic. We propose that new work and key historical studies both support the concept of a perivascular fluid system, whereby CSF enters the brain via PVS convective flow or dispersion along larger caliber arteries/arterioles, diffusion predominantly regulates CSF/ISF exchange at the level of the neurovascular unit associated with CNS microvessels, and, finally, a mixture of CSF/ISF/waste products is normally cleared along the PVS of venules/veins as well as other pathways; such a system may or may not constitute a true 'circulation', but, at the least, suggests a comprehensive re-evaluation of the previously proposed 'glymphatic' concepts in favour of a new system better taking into account basic cerebrovascular physiology and fluid transport considerations.

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Section: Diffusion or Flow Of The Isf In The Brain Ecs?mentioning

confidence: 99%

The role of brain barriers in fluid movement in the CNS: is there a ‘glymphatic’ system?

et al. 2018

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“…Many estimates of volume fraction have been made over the years, based on a variety of techniques including the analysis of electron micrographs, impedance measurements and radiotracer studies. An early impedance study by Horstmann & Meves (1959), together with electron micrographic evidence, suggested that the volume fraction was about 0 04. This estimate was contested in several papers by Van Harreveld and co-workers (Van Harreveld, Crowell & Malhotra, 1965;Van Harreveld & Malhotra, 1967;Van Harreveld, 1972) who claimed that the anatomical evidence was based on a misleading occlusion of extracellular spaces during the processing of the tissue and that the actual extracellular volume fractions were 0-18-0 25.…”

Section: Diffusion Of Ions In the Brain Diffusion In Agar And Brainmentioning

confidence: 99%

Ion diffusion modified by tortuosity and volume fraction in the extracellular microenvironment of the rat cerebellum.

Nicholson¹,

Phillips²

1981

The Journal of Physiology

755

685

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SUMMARY1. The validity of the macroscopic laws of ion diffusion was critically examined within the microenvironment of the extracellular space in the rat cerebellum using ion-selective micropipettes and ionophoretic point sources.2. The concepts of volume averaging, volume fraction (a) and tortuosity (A) were defined and shown to be theoretically appropriate for quantifying diffusion in a complex medium such as the brain.3. Diffusion studies were made with the cations tetramethylammonium and tetraethylammonium and the anions a-naphthalene sulphonate and hexafluoroarsenate, all of which remained essentially extracellular during the measurements. Diffusion parameters were measured for a period of 50 s and over distances of the order of 0-1 mm. 4. Measurements ofthe diffusion coefficients of the ions in agar gel gave values that were very close to those derivable from the literature, thus confirming the validity of the method.5. Measurements in the cerebellum did not reveal any systematic influences of ionophoretic current strength, electrode separation, anisotropy, inhomogeneity, charge discrimination or uptake, within the limits tested. 6. The pooled data from measurements with all the ions gave a = 0-21 +002 (mean+s.E. of mean) and A = 1-55+0-05 (mean+S.E. of mean).7. These results show that the extracellular space occupies about 20 % of the rat cerebellum and that the diffusion coefficient for small monovalent extracellular ions is reduced by a factor of 2-4 (i.e. A2) without regard to charge sign. The over-all effect of this is to increase the apparent strength of any ionic source in the cerebellum by a factor of A2/a, about 12-fold in the present case, and to modify the time course of diffusion.8. These conclusions confirm that the laws of macroscopic diffusion are closely obeyed in the cerebellum for small ions in the extracellular space, provided that volume fraction and tortuosity are explicitly taken into account. It is likely that these conclusions are generally applicable to other brain regions and other diffusing substances. PHY 321C. NICHOLSON AND J. M. PHILLIPS

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“…T h e trachea was exposed through a midline incision in the neck and a no. 18 T h e midventral incision was then continued down over the a b d o m e n and the skin was reflected on either side. A nick was m a d e in the chest wall at the left costophrenic angle.…”

Section: A T E R I a L S A N D M E T H O D Smentioning

confidence: 99%

“…Bargmann and Knoop used the method for fixation of the lung in amphibia and mammals (3,4) and of the neurohypophysis in kittens and dogs (5). Nylen and Scott (24) obtained fairly satisfactory fixation of growing teeth by means of perfusion, and Horstmann and Meves (18) mention that they used the method for fixing the brain of one kitten but do not provide any illustrations of their results. In addition to these scanty reports, however, it is known that several experienced investigators have attempted vascular perfusion with osmium tetroxide solutions, and that, being unable to obtain satisfactory results, they have abandoned it as a preparative technique.…”

Section: () the Journal Of Cell Biology • Volume ]2 1962mentioning

confidence: 99%

Fixation of Neural Tissues for Electron Microscopy by Perfusion With Solutions of Osmium Tetroxide

Palay

McGEE-RUSSELL

Gordon

et al. 1962

The Journal of Cell Biology

507

114

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This paper describes in detail a method for obtaining nearly uniform fixation of the nervous system by vascular perfusion with solutions of osmium tetroxide. Criteria are given for evaluating the degree of success achieved in the preservation of all the cellular components of the nervous system. The method permits analysis of the structural relations between cells at the electron microscopic level to an extent that has not been possible heretofore.

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Die Feinstruktur des molekularen Rindengraues und ihre physiologische Bedeutung

Cited by 201 publications

References 97 publications

The role of brain barriers in fluid movement in the CNS: is there a ‘glymphatic’ system?

The role of brain barriers in fluid movement in the CNS: is there a ‘glymphatic’ system?

Ion diffusion modified by tortuosity and volume fraction in the extracellular microenvironment of the rat cerebellum.

Fixation of Neural Tissues for Electron Microscopy by Perfusion With Solutions of Osmium Tetroxide

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