SWELLING OF GLIAL-CELLS IN LACTACIDOSIS AND BY GLUTAMATE - SIGNIFICANCE OF CL(-)-TRANSPORT

Swelling of glial and nerve cells is characteristic of brain damage in cerebral ischemia or trauma. The therapeutical efficiency of inhibiti on of Cl--transport by a novel antagonist, the diuretic torasemide, on cytotoxic swelling of glial cells from lactacidosis, or glutamate was analyzed. Lactacidosis and the interstitial accumulation of glutamate are hallmarks of the pathophysiological alterations in ischemic or tr aumatic brain tissue. C6 glioma cells harvested from culture and suspe nded in a physiological medium were either exposed to pH 6.2, or 5.0 b y lactic acid, or exposed to 1 mM glutamate at normal pH. Cell swellin g and viability were quantified by flow cytometry. Lactacidosis of pH 6.2 led to an increase in cell volume to 117.9 +/- 0.7% within 60 min. Torasemide (1 mM) inhibited the swelling response by 50% (P < 0.01). Cell swelling at pH 5.0, although more severe, was again attenuated by torasemide (P < 0.01). No effect was seen on the decrease in cell via bility at this level of acidosis. Addition of glutamate led to a stead y increase in cell volume which, contrary to cell swelling from lactac idosis, was not inhibited by torasemide. Inhibition of cell swelling f rom acidosis by this diuretic may be attributed to blocking of Cl-/HCO 3- exchange mechanisms activated by acidosis. The lack of effect by to rasemide in glial cell swelling from glutamate indicates operation of a different mechanism inducing cell swelling, for example cellular acc umulation of the amino acid together with Na+ and water.