Some Aspects of Acid-Base Metabolism in the Immature Central Nervous System

  • C. D. Withrow
Part of the Advances in Behavioral Biology book series (ABBI, volume 8)


Tissue acid-base metabolism is an important, but often neglected, area of investigation for several reasons. In the first place, the millieu in which cellular enzymatic reactions occur and in which many drug effects are exerted is intracellular fluid rather than extracellular fluid or blood. Second, tissue pH affects drug distribution, particularly if the drugs are weak electrolytes and non-ionic diffusion is an important determinant of their tissue-plasma ratios. Third, the processes, both active and passive, that are responsible for cellular hydrogen ion homeostasis are perhaps closely linked with other cellular activities of demonstrated significance, e.g., sodium transport. Finally, in the central nervous system (CNS), tissue acid-base balance is intimately related to cerebrospinal fluid (CSF) acid-base parameters and their regulation. Thus, it is appropriate to include a discussion of CNS and CSF acid-base metabolism in a symposium concerned with drug effects and distribution in the developing nervous system. There are, however, few data available concerned with acid-base regulation in the immature CNS and CSF. The purpose of this report is to summarize this information, and, more importantly, to point out what is not known about CNS acid-base balance in the immature animal. It is hoped that the questions not answered, and, in some cases not even directly proposed, will serve as a stimulus for more inquiry in this special research area.


Biochemical Development Immature Animal Carbonic Anhydrase Activity Fetal Lamb Immature Central Nervous System 
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  1. Addanki, S. and Sotos, J.F., 1969, Observations on intramitochondrial pH and ion transport by the 5, 5-dimethyl 2, 4-oxazolidinedione (DMO) method, Ann. N.Y. Acad. Sci. 147: 756.PubMedCrossRefGoogle Scholar
  2. Ames, A., III, Sakanoue, M. and Shinichiro, E., 1964, Na, K, Ca, Mg, and Cl concentrations in chroid plexus fluid and cisternal fluid compared with plasma ultrafiltrate, J. Neurophysiol. 27: 672.PubMedGoogle Scholar
  3. Brodie, D.A. and Woodbury, D.M., 1958, Acid-base changes in brain and blood of rats exposed to high concentrations of carbon dioxide, Am. J. Physiol. 192: 91.PubMedGoogle Scholar
  4. Fencl, V., 1971, Distribution of H+ and HCO8 in cerebral fluids. In: “Ion Homeostasis of the Brain”, (Siesjö and Sørensen, eds.), Academic Press, New York.Google Scholar
  5. Ferguson, R.K. and Woodbury, D.M., 1969, Penetration of 14C-inulin and 14C-sucrose into brain, cerebrospinal fluid, and skeletal muscle of developing rats, Exp. Brain Res. 7: 181.PubMedCrossRefGoogle Scholar
  6. Friede, R.L. and Hu, K., 1971, Hydrogen ion transfer and pH control in bowfin brain in vitro, Brain Res. 25: 161.PubMedCrossRefGoogle Scholar
  7. Granholm, L. and Pontén, U., 1969, The in vitro CO2 buffer curve of the intracellular space of cat cerebral cortex, Acta Neurol. Scand. 45: 493.PubMedCrossRefGoogle Scholar
  8. Grayman, G., Bradbury, M.W.B. and Kleeman, C.R., 1968, Intracellular pH of the amphibian brain incubated in vitro, Life Sci. 7: 499.PubMedCrossRefGoogle Scholar
  9. Herrington, R.T., Harned, H.S., Ferreiro, J.I. and Griffin, C.A., 1971, The role of the central nervous system in perinatal respiration studies of chemoregulatory mechanisms in the term lamb, Pediatrics 47: 857.PubMedGoogle Scholar
  10. Hertz, L., Schousboe, A. and Weiss, G.B., 1970, Estimation of ionic concentrations and intracellular pH in slices from different areas of rat brain, Acta Physiol. Scand. 79: 506.PubMedCrossRefGoogle Scholar
  11. Hodson, W.A., Fenner, A., Brumley, G., Chernick, V. and Avery, M.E., 1968, Cerebrospinal fluid and blood acid-base relationships in fetal and neonatal lambs and pregnant ewes, Res. Physiol. 4: 322.CrossRefGoogle Scholar
  12. Kibler, R.F., O’Neill, R.P. and Robin, E.D., 1964, Intracellular acid-base relations of dog brain with reference to the brain extracellular volume, J. Clin. Invest. 43: 431.PubMedCrossRefGoogle Scholar
  13. Kjällquist, A., Messeter, K. and Siesjö, B.K, 1970, The in vivo CO2 buffer capacity of rat brain tissue under carbonic anhydrase inhibition, Acta Physiol. Scand. 78: 94.PubMedCrossRefGoogle Scholar
  14. Koch, A. and Woodbury, D.M., 1960, Carbonic anhydrase inhibition and brain electrolyte composition, Am. J. Physiol. 198: 434.PubMedGoogle Scholar
  15. Leusen, I., 1972, Regulation of cerebrospinal fluid composition with reference to breathing, Physiol. Rev. 52: 1.PubMedGoogle Scholar
  16. Maklâri, E. and Kovâch, A.G.B., 1968, Carbon dioxide content of brain tissue and acid-base balance in haemorrhagic shock after pretreatment with dibenzyline, Acta Medica Academiae Scientiarum Ungaricae 25: 13.Google Scholar
  17. Messeter, K. and Siesjö, B.K., 1971, Electrochemical gradients for H+ and HCO3 between blood and CSF during sustained acid-base changes. In: “Ion Homeostasis of the Brain,” (Siesjö and Sørenson, eds.), Academic Press, New York.Google Scholar
  18. Messeter, K. and Siesjö, B.K., 1970, Regulation of intracellular pH in the rat brain in chronic hypercapnia, Acta Physiol. Scand. 79: 136.PubMedCrossRefGoogle Scholar
  19. Millichap, J.G., 1957, Development of seizure patterns in newborn animals. Significance of brain carbonic anhydrase, Proc. Soc. Exp. Biol. Med. 97: 125.Google Scholar
  20. Millichap, J.G., Balter, M. and Hernandez, P., 1958, Development of susceptibility to seizures in young animals III. Brain water, electrolyte and acid-base metabolism, Proc. Soc. Exp. Biol. Med. 99: 6.PubMedGoogle Scholar
  21. Miner, L.C. and Reed, D.J., 1972, Composition of fluid obtained from choroid plexus tissue isolated in a chamber in situ, J. Physiol. 227: 127.PubMedGoogle Scholar
  22. Mines, A.H. and Sorensen, S.C., 1971, Changes in the electrochemical potential difference for HCO3 between blood and cerebrospinal fluid and in cerebrospinal fluid lactate concentration during isocarbic hypoxia, Acta Physiol. Scand. 81: 225.PubMedCrossRefGoogle Scholar
  23. Mines, A.H., Morril, C.G. and Sorensen, S.C., 1971, The effect of iso- carbic metabolic acidosis in blood on (H+) and HC0) in CSF with deductions about the regulation of an active transport of H+/HCOq between blood and CSF, Acta Physiol. Scand. 81: 234.PubMedCrossRefGoogle Scholar
  24. Nichols, G., Jr., 1958, Serial changes in tissue carbon dioxide content during acute respiratory acidosis, J. Clin. Invest. 37:1111PubMedCrossRefGoogle Scholar
  25. Pannier, J.L., Weyne, J. and Leusen, I., 1971, The CSF blood potential and the regulation of the bicarbonate concentration of CSF during acidosis in the cat, Life Sci. 10: 287.CrossRefGoogle Scholar
  26. Pontén, U. and Siesjö, B.K., 1964a, A method for the determination of total carbon dioxide content of frozen tissues, Acta Physiol. Scand. 60: 297.CrossRefGoogle Scholar
  27. Pontén, U. and Siesjö, B.D., 1964b, Acid-labile carbon dioxide of rat brain after freezing the tissue in situ, Acta Physiol. Scand. 60: 309.CrossRefGoogle Scholar
  28. Robin, E.D., Murdaugh, H.V., Jr., and Weiss, E., 1964, Acid-base, fluid and electrolyte metabolism in the elasmonbranch, I. Ionic composition of erythrocytes, muscle and brain, J. Cell Comp. Physiol. 64: 409.CrossRefGoogle Scholar
  29. Rollins, D.E., Withrow, C.D. and Woodbury, D.M., 1970, Tissue acidbase balance in acetazolamide-treated rats, J. Pharmac. Exp. Ther. 174: 535.Google Scholar
  30. Roos, A., 1971, Intracellular pH and buffering power of rat brain, Am. J. Physiol. 221: 176.PubMedGoogle Scholar
  31. Roos, A., 1965, Intracellular pH and intracellular buffering power of the cat brain, Am. J. Physiol. 209: 1233.PubMedGoogle Scholar
  32. Siesjö, B.K., 1972, The regulation of cerebrospinal fluid pH, Kidney International 1: 360.PubMedCrossRefGoogle Scholar
  33. Siesjö, B.K. and Kjällquist, A., 1969, A new theory for the regulation of the extracellular pH in the brain, Scand. J. Clin. Lab. Invest. 24: 1.PubMedCrossRefGoogle Scholar
  34. Siesjö, B.K. and Messeter, K., 1971, Factors determining intracellular pH. In: “Ion Homeostasis of the Brain,” (Siesjö and Sørensen, eds.), Academic Press, New York.Google Scholar
  35. Siesjö, B.K. and Pontén, U., 1966a, Intracellular pH - True parameter or misnomer?, Ann. N.Y. Acad. Sci. 133: 78.CrossRefGoogle Scholar
  36. Siesjö, B.K. and Pontên, U., 1966b, Acid-base changes in the brain in nonrespiratory acidosis and alkalosis, Exp. Br. Res. 2: 176.CrossRefGoogle Scholar
  37. Siesjö, B.K. and Sorensen, S.C., eds., 1971, “Ion Homeostasis of the Brain,” Academic Press, New York.Google Scholar
  38. Thompson, A.M. and Brown, E.B., Jr., 1960, Tissue carbon dioxide concentrations in rats during acute respiratory acidosis, J. Appl. Physiol. 15: 49.PubMedGoogle Scholar
  39. Waddell, W.J., 1972, Subcellar and molecular aspects of intracellular pH, Chest 61: 56S.Google Scholar
  40. Waddell, W.J. and Bates, R.G., 1969, Intracellular pH, Physiol. Rev. 49: 285.PubMedGoogle Scholar
  41. Weyne, J., Demeester, G. and Leusen, I., 1968, Bicarbonate and chloride shifts in rat brain during acute and prolonged respiratory acid-base changes, Arch. Int. Physiol. et de Biochimie 76: 415.CrossRefGoogle Scholar
  42. Weyne, J., Pannier, J.L., Demeester, G. and Leusen, I., 1970, Bicarbonate and chloride of rat brain during infusion-induced changes in bicarbonate concentration of blood, Pflugers Arch. 320: 45.PubMedCrossRefGoogle Scholar
  43. Wills, M.R., 1970, Fundamental physiological role of parathyroid hormone in acid-base homeostasis, Lancet 2: 802.PubMedCrossRefGoogle Scholar
  44. Withrow, C.D. and Woodbury, D.M., 1964, Tissue acid-base changes during maturation. In: “Progress in Brain Research,” (Himwich and Himwich, eds.), Vol. 9, Elsevier Publishing Company, Amsterdam.Google Scholar
  45. Withrow, C.D., Woodbury, D.M. and Wilcox, W.D., 1964, Acid-base changes in brain and skeletal muscle of maturing rats, Am. J. Physiol. 206: 521.PubMedGoogle Scholar
  46. Withrow, C.D., Elsmore, T., Williams, J.A. and Woodbury, D.M., 1971, Hydrogen ion distribution and regulation in various rat tissues. In: “Ion Homeostasis of the Brain,” (Siesjö and Sorensen, eds.), Academic Press, New York.Google Scholar
  47. Woodbury, J.W., 1971, Fluxes of H+ and HCO3 across frog skeletal muscle cell membrane. In: “Ion Homeostasis of the Brain,” (Siesjö and Sorensen, eds.), Academic Press, New York.Google Scholar

Copyright information

© Plenum Press, New York 1974

Authors and Affiliations

  • C. D. Withrow
    • 1
  1. 1.Department of Pharmacology, College of MedicineUniversity of UtahSalt Lake CityUSA

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