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Stimulation-Induced Decreases in the Diffusion of Extra-vascular Water in the Human Visual Cortex: a Window in Time and Space on Mechanisms of Brain Water Transport and Economy

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Abstract

In a human magnetic resonance diffusion-weighted imaging (DWI) investigation at 3 T and high diffusion sensitivity weighting (b = 1,800 s/mm2), which emphasizes the contribution of water in the extra-vascular compartment and minimizes that of the vascular compartment, we observed that visual stimulation with a flashing checkerboard at 8 Hz for a period of 600 s in eight subjects resulted in significant increases in DWI signals (mean +2.70%, range +0.51 to 8.54%). The increases in DWI signals in activated areas of the visual cortex indicated that during stimulation, the apparent diffusion coefficient (ADC) of extra-vascular compartment water decreased. In response to continuous stimulation, DWI signals gradually increased from pre-stimulation controls, leveling off after 400–500 s. During recovery from stimulation, DWI signals gradually decreased, approaching control levels in 300–400 s. In this study, we show for the first time that the effects of visual stimulation on DWI signals in the human visual cortex are cumulative over an extended period of time. We propose that these relatively slow stimulation-induced changes in the ADC of water in the extra-vascular compartment are due to transient changes in the ratio of faster diffusing free water to slower diffusing bound water and reflect brain water transport processes between the vascular and extra-vascular compartments at the cellular level. The nature of these processes including possible roles of the putative glucose water import and N-acetylaspartate water export molecular water pumps in brain function are discussed.

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Abbreviations

ADC:

Apparent diffusion coefficient

AQP4:

Aquaporin 4

ASPA:

Aspartoacylase

BOLD:

Blood oxygenation level dependent

CD:

Canavan disease

D :

Diffusion coefficient

DWI:

Diffusion-weighted imaging

ECF:

Extracellular fluid

fMRI:

Functional magnetic resonance imaging

Glc:

Glucose

Hz:

Hertz

MWP:

Molecular water pump

NAA:

N-Acetylaspartate

ROI:

Region of interest

T:

Tesla

References

  • Agre P, King LS, Yasui M, Guggino WB, Ottersen OP, Fujiyoshi Y, Engel A, Neilsen S (2002) Aquaporin water channels—from atomic structure to clinical medicine. J Physiol 542:3–16

    Article  PubMed  CAS  Google Scholar 

  • Andrew RD, Labron MW, Boehnke SE, Carnduff L, Kirov SA (2007) Physiological evidence that pyramidal neurons lack functional water channels. Cereb Cortex 17:787–802

    Article  PubMed  Google Scholar 

  • Bammer R, Stollberger R, Augustin M, Simbrunner J, Offenbacher H, Kooijman H, Ropele S, Kapeller P, Wach P, Ebner F, Fazekas F (1999) Diffusion-weighted imaging with navigated interleaved echo-planar imaging and a conventional gradient system. Radiology 211:799–806

    PubMed  CAS  Google Scholar 

  • Baslow MH (1998) Function of the N-acetyl-L-histidine system in the vertebrate eye. Evidence in support of a role as a molecular water pump. J Mol Neurosci 10:193–208

    Article  PubMed  CAS  Google Scholar 

  • Baslow MH (1999) The existence of molecular water pumps in the nervous system. A review of the evidence. Neurochem Int 34:77–90

    Article  PubMed  CAS  Google Scholar 

  • Baslow MH (2010) Evidence that the tri-cellular metabolism of N-acetylaspartate functions as the brain’s “operating system”: how NAA metabolism supports meaningful intercellular frequency-encoded communications. Amino Acids 39(5):1139–1145

    Article  PubMed  CAS  Google Scholar 

  • Baslow MH, Guilfoyle DN (2002) Effect of N-acetylaspartic acid on the diffusion coefficient of water: a proton magnetic resonance phantom method for measurement of osmolyte-obligated water. Analyt Biochem 311(2):133–138

    Article  PubMed  CAS  Google Scholar 

  • Baslow MH, Guilfoyle DN (2007) Using proton magnetic resonance imaging and spectroscopy to understand brain “activation”. Brain Lang 102:153–164

    Article  PubMed  Google Scholar 

  • Baslow MH, Hrabe J, Guilfoyle DN (2007) Dynamic relationship between neurostimulation and N-acetylaspartate metabolism in the human visual cortex. Evidence that NAA functions as a molecular water pump during visual stimulation. J Mol Neurosci 32:235–245

    Article  PubMed  CAS  Google Scholar 

  • Buffoli B (2010) Aquaporin biology and nervous system. Curr Neuropharmacol 8:97–104

    Article  Google Scholar 

  • Choe S, Rosenberg JM, Abramson J, Wright EM, Grabe M (2010) Water permeation through the sodium-dependent galactose cotransporter vSGLT. Biophys J 99(7):L56–L58

    Article  PubMed  CAS  Google Scholar 

  • Darquie A, Poline J-B, Poupon C, Saint-Jalmes H, Le Bihan D (2001) Transient decrease in water diffusion observed in human occipital cortex during visual stimulation. PNAS 98:9391–9395

    Article  PubMed  CAS  Google Scholar 

  • Foglio E, Rodella LF (2010) Aquaporins and neurodegenerative diseases. Curr Neuropharmacol 8:112–121

    Article  PubMed  CAS  Google Scholar 

  • Frahm J, Kruger G, Merboldt KD, Kleinschmidt A (1996) Dynamic uncoupling and recoupling of perfusion and oxidative metabolism during focal brain activation in man. Magn Reson Med 35:143–148

    Article  PubMed  CAS  Google Scholar 

  • Kvittingen EA, Guldal G, Borsting S, Skalpe IO, Stokke O, Jellum E (1986) N-acetylaspartic aciduria in a child with a progressive cerebral atrophy. Clin Chim Acta 158:217–227

    Article  PubMed  CAS  Google Scholar 

  • Le Bihan D, Urayama S, Toshihiko A, Hanakawa T, Fukuyama H (2006) Direct and fast detection of neuronal activation in the human brain with diffusion MRI. PNAS 103:8263–8268

    Article  PubMed  Google Scholar 

  • Liu Z, Zheng D, Wang X, Zhang J, Xie S, Xiao J, Jiang X (2011) Apparent diffusion coefficients of metabolites in patients with MELAS using diffusion-weighted MR spectroscopy. Am J Neuroradiol 32:898–902

    Article  PubMed  CAS  Google Scholar 

  • Mangia S, Tkac I, Gruetter R, Van de Moortele P-F, Maraviglia B, Ugurbil K (2007) Sustained neuronal activation raises oxidative metabolism to a new steady-state level: evidence from 1H NMR spectroscopy in the human visual cortex. J Cereb Blood Flow Metab 27:1055–1063

    PubMed  CAS  Google Scholar 

  • Meinild A-K, Klaerke DA, Loo DDF, Wright EM, Zeuthen T (1998) The human Na+-glucose cotransporter is a molecular water pump. J Physiol 508:15–21

    Article  PubMed  CAS  Google Scholar 

  • Niendorf T, Dijkhuizen RM, Norris DG, van Lookeren Campagne M, Nicolay K (1996) Biexponential diffusion attenuation in various states of brain tissue: implications for diffusion weighted imaging. Magn Reson Med 36:847–857

    Article  PubMed  CAS  Google Scholar 

  • Pfeuffer J, Tkac I, Gruetter R (2000) Extracellular-intracellular distribution of glucose and lactate in the rat brain assessed noninvasively by diffusion-weighted 1H nuclear magnetic resonance spectroscopy in vivo. J Cereb Blood Flow Metab 20:736–746

    Article  PubMed  CAS  Google Scholar 

  • Plumridge TH, Waigh RD (2002) Water structure theory and some implications for drug design. J Pharm Pharmacol 54:1155–1179

    Article  PubMed  CAS  Google Scholar 

  • Pradhan S, Goyal G (2011) Teaching NeuroImages: honeycomb appearance of the brain in a patient with Canavan disease. Neurology 76:e68

    Article  PubMed  Google Scholar 

  • Reese TG, Heid O, Weisskoff RM, Wedeen VJ (2003) Reduction of eddy current induced distortion in diffusion MRI using a twice refocused spin echo. Magn Reson Med 49:177–182

    Article  PubMed  CAS  Google Scholar 

  • Sarchielli P, Tarducci R, Presciutti O, Gobbi G, Pelliccioli GP, Stipa G, Alberti A, Capocchi G (2005) Functional 1H-MRS findings in migraine patients with and without aura assessed interictally. Neuroimage 24:1025–1031

    Article  PubMed  Google Scholar 

  • Tait MJ, Saadoun S, Bell BA, Papadopoulos MC (2008) Water movements in the brain: role of aquaporins. Trends Neurosci 31(1):37–43

    Article  PubMed  CAS  Google Scholar 

  • Wheatley DN (1998) Diffusion theory, the cell and the synapse. Biosystems 45:151–163

    Article  PubMed  CAS  Google Scholar 

  • Wiame E, Tyteca D, Pierrot N, Collard F, Amyere M, Noel G, Desmedt J, Nassogne M-C, Vikkula M, Octave J-N, Vincent M-F, Courtoy PJ, Boltshauser E, Van Shaftingen E (2010) Molecular identification of aspartate N-acetyltransferase and its mutation in hypoacetylaspartia. Biochem J 425:127–136

    Article  CAS  Google Scholar 

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Correspondence to Morris H. Baslow.

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Baslow, M.H., Hu, C. & Guilfoyle, D.N. Stimulation-Induced Decreases in the Diffusion of Extra-vascular Water in the Human Visual Cortex: a Window in Time and Space on Mechanisms of Brain Water Transport and Economy. J Mol Neurosci 47, 639–648 (2012). https://doi.org/10.1007/s12031-011-9700-6

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  • DOI: https://doi.org/10.1007/s12031-011-9700-6

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