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J.M. Phillips

Bio: J.M. Phillips is an academic researcher from New York University. The author has contributed to research in topics: Diffusion (business) & Tortuosity. The author has an hindex of 5, co-authored 5 publications receiving 1027 citations.

Papers
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Journal ArticleDOI
TL;DR: The 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.
Abstract: 1. 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 (alpha) and tortuosity (lambda) 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 alpha-naphthalene sulphonate and hexafluoro-arsenate, all of which remained essentially extracellular during the measurements. Diffusion parameters were measured for a period of 50s and over distances of the order of 0.1 mm. 4. Measurements of the 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 alpha = 0.21 +/- 0.02 (mean +/- S.E. of mean) and lambda = 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. lambda 2) 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 lambda 2/alpha, 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.

767 citations

Journal ArticleDOI
TL;DR: It is shown both theoretically and experimentally that the above solution must be generalized for iontophoresis of ions which are confined to the extracellular space of the brain and that K ÷ behaves anomalously and therefore probably migrates by transcellular routes.

156 citations

Journal ArticleDOI
TL;DR: The experiments indicate an anion channel of defined size becomes active during SD and that the size is apparently larger than that of some, but not all, inhibitory channels found in the mammalian central nervous system, and direct evidence that the extracellular space shrinks during SD is provided.

124 citations

Book ChapterDOI
01 Jan 1981
TL;DR: The use of anions, novel to the brain, are described as probes for the diffusion properties of the extracellular space, and as indicators ofextracellular volume changes and changes in membrane permeability during spreading depression.
Abstract: The dynamic behavior of the extracellular ions of the brain has been revealed with a new clarity through the use of ion-selective micropipettes (ISMs) Numerous studies have revealed changes in [K+]0, [Ca2+]0, [Na+]0 and [Cl-]0 (see ref. 10 for review). One can go beyond the study of these endogenous brain ions, however, by the introduction of exogenous ionic “probes”, and the subsequent monitoring of their behavior with appropriately chosen ion exchangers in ISMs. In this paper we describe the use of anions, novel to the brain, as probes for the diffusion properties of the extracellular space, and as indicators of extracellular volume changes and changes in membrane permeability during spreading depression.

5 citations


Cited by
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Journal ArticleDOI
TL;DR: The concepts behind diffusion tensor imaging are reviewed and potential applications, including fiber tracking in the brain, which, in combination with functional MRI, might open a window on the important issue of connectivity.
Abstract: The success of diffusion magnetic resonance imaging (MRI) is deeply rooted in the powerful concept that during their random, diffusion-driven displacements molecules probe tissue structure at a microscopic scale well beyond the usual image resolution. As diffusion is truly a three-dimensional process, molecular mobility in tissues may be anisotropic, as in brain white matter. With diffusion tensor imaging (DTI), diffusion anisotropy effects can be fully extracted, characterized, and exploited, providing even more exquisite details on tissue microstructure. The most advanced application is certainly that of fiber tracking in the brain, which, in combination with functional MRI, might open a window on the important issue of connectivity. DTI has also been used to demonstrate subtle abnormalities in a variety of diseases (including stroke, multiple sclerosis, dyslexia, and schizophrenia) and is currently becoming part of many routine clinical protocols. The aim of this article is to review the concepts behind DTI and to present potential applications.

3,353 citations

Journal ArticleDOI
18 Oct 2013-Science
TL;DR: It is reported that sleep has a critical function in ensuring metabolic homeostasis and convective fluxes of interstitial fluid increased the rate of β-amyloid clearance during sleep, suggesting the restorative function of sleep may be a consequence of the enhanced removal of potentially neurotoxic waste products that accumulate in the awake central nervous system.
Abstract: The conservation of sleep across all animal species suggests that sleep serves a vital function. We here report that sleep has a critical function in ensuring metabolic homeostasis. Using real-time assessments of tetramethylammonium diffusion and two-photon imaging in live mice, we show that natural sleep or anesthesia are associated with a 60% increase in the interstitial space, resulting in a striking increase in convective exchange of cerebrospinal fluid with interstitial fluid. In turn, convective fluxes of interstitial fluid increased the rate of β-amyloid clearance during sleep. Thus, the restorative function of sleep may be a consequence of the enhanced removal of potentially neurotoxic waste products that accumulate in the awake central nervous system.

3,303 citations

Journal ArticleDOI
TL;DR: Experimental studies with the real-time iontophoresis method employing the cation tetramethylammonium in normal brain tissue improve the conception of ECS structure and the roles of glia and extracellular matrix in modulating the ECS microenvironment.
Abstract: Diffusion in the extracellular space (ECS) of the brain is constrained by the volume fraction and the tortuosity and a modified diffusion equation represents the transport behavior of many molecule...

1,215 citations

Journal ArticleDOI
TL;DR: The hypothesis predicts that loss of cellular calcium ho­ meostasis underlies selective neuronal vulnerability in ischemia, hypoglycemia, and epileptic seizures and that some cells are more vulner­ able than others because they have a higher density of calcium channels in their plasma membranes.
Abstract: It has been commonly assumed that calcium, which normally serves important functions as a membrane stabilizer, metabolic regulator, and sec­ ond messenger, also can mediate anoxic and toxic cell death (Schanne et aI., 1979; Farber, 1981; Trump et aI., 1981). It is then postulated that when the plasma membrane becomes unduly permeable to calcium, the free cytosolic concentration (Ca2+) rises to toxic levels. As applied to the brain, this hypothesis predicts that loss of cellular calcium ho­ meostasis underlies selective neuronal vulnerability in ischemia, hypoglycemia, and epileptic seizures (Siesj6, 1981; Meldrum, 1983; Raichle, 1983; for further literature, see Siesj6 and Wieloch, 1985; Siesj6, 1988). It should be clearly understood that ischemia, particularly if dense, causes all cells to loose their calcium homeostasis. The hypothesis predicts, therefore, that some cells are more vulner­ able than others because they have a higher density of calcium channels in their plasma membranes. Presumably, this could lead to untolerable local in­ creases in calcium concentration. In a recent extension of the calcium hypothesis, it was speculated that increased calcium cycling across ischemia-damaged membranes leads to a sustained rise in Ca2 + j and slow calcium overload of mitochondria, thereby causing delayed neuronal death (Deshpande et aI., 1987; see also Martins et aI., 1988). Dux et aI. (1987), inducing transient isch­ emia in the gerbil, recently assessed the time course of mitochondrial calcium deposits in glia cells and in pyramidal cells of the hippocampus CAl sector and

1,212 citations