Hypo-osmotic swelling-activated release of organic osmolytes in brain slices: implications for brain oedema in vivo

J Neurochem. 2001 Jun;77(6):1632-40. doi: 10.1046/j.1471-4159.2001.00403.x.


A decrease in the intracellular levels of osmotically active species has invariably been seen after swelling of mammalian brain tissue preparations. The exact identity of the species, and the manner of their decrease, remain to be described. We investigated the swelling-activated decrease of organic osmolytes in rat cortical brain slices using (1)H- and (31)P-magnetic resonance spectroscopy. We found that acute hypo-osmotic shock causes decreases in the levels of a range of intracellular amino acids and amino acid derivatives, N-acetyl-aspartate, creatine, GABA, glutamate, hypotaurine, and also in the levels of the methylamines glycerol-phosphorylcholine, phosphorylcholine and choline. Incubation of cortical slices with the anion channel blockers niflumic acid and tamoxifen caused inhibition of organic osmolyte efflux, suggesting that such osmolyte efflux occurs through anion channels. Intracellular phosphocreatine was also seen to decrease during acute hypo-osmotic superfusion, although intracellular ATP remained constant. In addition, the acidification of an intracellular compartment was observed during hypo-osmotic superfusion. Our results suggest a link between brain energy reserve and brain osmoregulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Anions / metabolism
  • Antineoplastic Agents, Hormonal / pharmacology
  • Brain Edema / metabolism*
  • Cerebral Cortex / metabolism*
  • Cyclooxygenase Inhibitors / pharmacology
  • Female
  • Hypotonic Solutions
  • Ion Channels / antagonists & inhibitors
  • Isotonic Solutions / pharmacology
  • Magnetic Resonance Spectroscopy
  • Niflumic Acid / pharmacology
  • Organ Culture Techniques
  • Osmotic Pressure*
  • Phosphocreatine / metabolism
  • Phosphorus Isotopes
  • Protons
  • Rats
  • Rats, Wistar
  • Tamoxifen / pharmacology


  • Anions
  • Antineoplastic Agents, Hormonal
  • Cyclooxygenase Inhibitors
  • Hypotonic Solutions
  • Ion Channels
  • Isotonic Solutions
  • Phosphorus Isotopes
  • Protons
  • Phosphocreatine
  • Tamoxifen
  • Niflumic Acid
  • Adenosine Triphosphate