The authors thank Nancy Cruz for her expert technical assistance and Donna Brackett for help in the preparation of the manuscript. This study was supported by the National Institute of Neurological Diseases and Stroke (grant NS-32059) and grants from the University of Wisconsin Departments of Anesthesiology and Neurological Surgery.

  • 1
    Ackerman J.J.H., Berkowitz B.A., Deuel R.K. (1984a) Phosphorus-31 NMR of rat brain in vivo with bloodless perfluorocarbon perfused rat.Biochem. Biophys. Res. Commun. 119,913919.
  • 2
    Ackerman J.J.H., Evelhoch J.L., Berkowitz B.A., Kichura G.M., Deuel R.K., Lown K.S. (1984b) Selective suppression of the cranial bone resonance from 31P NMR experiments with rat brain in vivo. J. Magn. Res. 56,318322.
  • 3
    Ackerman J.J.H., Soto G.E., Spees W.M., Zhu Z., Evelhoch J.L. (1996) The NMR chemical shift pH measurement revisited : analysis of error and modeling of a pH dependent reference.Magn. Res. Med. 36,674683.
  • 4
    Altman P.L. & Dittmer D.S. (1974) Biology Data Book, pp. 100101. Federation of American Societies for Experimental Biology, Bethesda.
  • 5
    Ammann D., Lanter F., Steiner R.A., Schulthess P., Shijo Y., Simon W. (1981) Neutral carrier based hydrogen ion selective microelectrode for extra- and intracellular studies.Anal. Chem. 53,22672269.
  • 6
    Benveniste H., Drejer J., Schousboe A., Diemer N.H. (1984) Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis.J. Neurochem. 43,13691374.
  • 7
    Bradley R.D. & Semple S.J. (1962) A comparison of certain acid-base characteristic of arterial blood, jugular venous blood and cerebrospinal fluid in man, and the effect on them of some acute and chronic acid-base disturbances.J. Physiol. (Lond.) 160,381391.
  • 8
    Bungay P.M., Morrison P.F., Dedrick R.L. (1990) Steady-state theory for quantitative microdialysis of solutes and water in vivo and in vitro.Life Sci. 46,105119.
  • 9
    Corbett R.J., Laptook A.R., Nunnally R.L. (1987) The use of the chemical shift of the phosphomonoester P-31 magnetic resonance peak for the determination of intracellular pH in the brains of neonates.Neurology 37,17711779.
  • 10
    Davies K.R., Finnegan W., Richardson G., Acuff V., Fenstermacher J.D. (1997) How many capillaries does it take to make a venule ?Soc. Neurosci. Abstr. 23,1574.
  • 11
    Duong T.Q., Ying H.S., Neil J.J. (1998) Evaluation of extra-and intracellular apparent diffusion in normal and globally ischemic rat brain via 19F NMR. Magn. Res. Med. 40,113.
  • 12
    Fishman R.A. (1980) Cerebrospinal Fluid in Diseases of the Nervous System, pp. 5051. Saunders, Philadelphia.
  • 13
    Fitzpatrick J.H.J, Kintner D., Anderson M., Westler W.M., Emoto S.E., Gilboe D.D. (1996) NMR studies of Pi-containing extracellular and cytoplasmic compartments in brain. J. Neurochem. 66,26122620.
  • 14
    Gilboe D.D., Kintner D., Anderson M.E., Fitzpatrick J.H., Emoto S.E., Markley J.L. (1993) Inorganic phosphate compartmentation in the normal isolated canine brain.J. Neurochem. 60,21922203.
  • 15
    Harris R.J. & Symon L. (1984) Extracellular pH, potassium, and calcium activities in progressive ischaemia of rat cortex.J. Cereb. Blood Flow Metab. 4,178186.
  • 16
    Hellums J.D., Nair P.K., Huang N.S., Ohshima N. (1996) Simulation of intraluminal gas transport processes in the microcirculation.Ann. Biomed. Eng. 24,124.
  • 17
    Hoffman W.E., Charbel F.T., Edelman G. (1996) Brain tissue oxygen, carbon dioxide, and pH in neurosurgical patients at risk for ischemia.Anesth. Analg. 82,582586.
  • 18
    Javaheri S., De Hemptinne A., Vanheel B., Leusen I. (1983a) Changes in brain ECF pH during metabolic acidosis and alkalosis : a microelectrode study.J. Appl. Physiol. 55,18491853.
  • 19
    Javaheri S., Weyne J., Demeester G. (1983b) Changes in the brain surface pH and cisternal cerebrospinal fluid acid-base variables in respiratory arrest.Respir. Physiol. 51,3143.
  • 20
    Katsura K., Ekholm A., Asplund B., Siesjö B.K. (1991) Extracellular pH in the brain during ischemia : relationship to the severity of lactic acidosis.J. Cereb. Blood Flow Metab. 11,597599.
  • 21
    Katsura K., Asplund B., Ekholm A., Siesjö B.K. (1992) Extra-and intracellular pH in the brain during ischaemia, related to tissue lactate content in normo- and hypercapnic rats.Eur. J. Neurosci. 4,166176.
  • 22
    Katsura K., Kristian T., Nair R., Siesjö B.K. (1994) Regulation of intra-and extracellular pH in the rat brain in acute hypercapnia : a re-appraisal.Brain Res. 651,4756.
  • 23
    Kauppinen R.A., Williams S.R., Busza A.L., Van Bruggen N. (1993) Applications of magnetic resonance spectroscopy and diffusion-weighted imaging to the study of brain biochemistry and pathology.Trends Neurosci. 16,8895.
  • 24
    Kraig R.P., Ferreira-Filho C.R., Nicholson C. (1983) Alkaline and acid transients in cerebellar microenvironment.J. Neurophysiol. 49,831850.
  • 25
    Lagerwall K., Daneryd P., Schersten T., Soussi B. (1995) In vivo 31P nuclear magnetic resonance evidence of the salvage effect of ascorbate on the postischemic reperfused rat skeletal muscle. Life Sci. 56,389397.
  • 26
    Lambertsen C.J. (1960) Carbon dioxide and respiration in acid-base homeostasis.Anesthesiology 21,642651.
  • 27
    Ljunggren B., Schutz H., Siesjö B.K. (1974) Changes in energy state and acid-base parameters of the rat brain during complete compression ischemia.Brain Res. 73,277289.
  • 28
    McKinley B.A., Morris W.P., Parmley C.L., Butler B.D. (1996) Brain parenchyma pO2, pCO2, and pH during and after hypoxic, ischemic brain insult in dogs.Crit. Care. Med. 24,18581868.
  • 29
    Moon R.B. & Richards J.H. (1973) Determination of intracellular pH by 31P magnetic resonance. J. Biol. Chem. 248,72767278.
  • 30
    Murphy-Boesch J. & Koretsky A.P. (1983) An in vivo NMR probe circuit for improved sensitivity.J. Magn. Res. 54,526532.
  • 31
    Mutch W.A. & Hansen A.J. (1984) Extracellular pH changes during spreading depression and cerebral ischemia : mechanisms of brain pH regulation.J. Cereb. Blood Flow Metab. 4,1727.
  • 32
    Nedergaard M., Kraig R.P., Tanabe J., Pulsinelli W.A. (1991) Dynamics of interstitial and intracellular pH in evolving brain infarct.Am. J. Physiol. 260,R581R588.
  • 33
    Ohno M., Obrenovitch T.P., Hartell N., Barratt S., Bachelard H.S., Symon L. (1989) Simultaneous recording of tissue pCO2, interstitial pH and potassium activity in the rat cerebral cortex during anoxia and the subsequent recovery period.Neurol. Res. 11,153159.
  • 34
    Pappenheimer J.R., Fencl V., Heisey S.R., Held D. (1965) Role of cerebral fluids in control of respiration as studied in unanesthetized goats.Am. J. Physiol. 208,436450.
  • 35
    Pontén U. & Siesjö B.K. (1966) Gradients of CO2 tension in the brain.Acta Physiol. Scand. 67,129140.
  • 36
    Portman M.A., Lassen N.A., Cooper T.G., Sills A.M., Potchen E.J. (1991) Intra-and extracellular pH of the brain in vivo studied by 31P-NMR during hyper- and hypocapnia. J. Appl. Physiol. 71,21682172.
  • 37
    Scheller D., Kolb J., Tegtmeier F., Lehmenkuhler A. (1992) Extracellular changes of inorganic phosphate are different during spreading depression and global cerebral ischemia of rats.Neurosci. Lett. 141,269272.
  • 38
    Siesjö B.K., Von Hanwehr R., Nergelius G., Nevander G., Ingvar M. (1985) Extra- and intracellular pH in the brain during seizures and in the recovery period following the arrest of seizure activity.J. Cereb. Blood Flow Metab. 5,4757.
  • 39
    Soto G.E., Zhu Z., Evelhoch J.L., Ackerman J.J.H. (1996) Tumor 31P NMR pH measurements in vivo : a comparison of inorganic phosphate and intracellular 2-deoxyglucose-6-phosphate as pH NMR indicators in murine radiation-induced fibrosarcoma-1. Magn. Res. Med. 36,698704.
  • 40
    Szerb J.C. & Redondo I.M. (1993) Astrocytes and the entry of circulating ammonia into the brain : effect of fluoroacetate.Metab. Brain Disord. 8,217234.
  • 41
    Taylor D.L., Obrenovitch T.P., Symon L. (1996) Changes in extracellular acid-base homeostasis in cerebral ischemia.Neurochem. Res. 21,10131021.
  • 42
    Van der Ploeg C.P., Dankelman J., Spaan J.A. (1994) Classical Krogh model does not apply well to coronary oxygen exchange.Adv. Exp. Med. Biol. 345,299304.
  • 43
    Waterfall A.H., Singh G., Fry J.R., Marsden C.A. (1995) Detection of the lipid peroxidation product malonaldehyde in rat brain in vivo.Neurosci. Lett. 200,6972.
  • 44
    Waterfall A.H., Singh G., Fry J.R., Marsden C.A. (1996) Acute acidosis elevates malonaldehyde in rat brain in vivo.Brain Res. 712,102106.