Effect of lactacidosis on cell volume and intracellular pH of astrocytes

Acute traumatic or ischemic cerebral Lesions are associated with tissue aci dosis leading to cytotoxic brain edema, predominantly affecting :astrocytes . Glial swelling from acidosis is believed to be the attempt of cells to ma intain a physiological intracellular pH (pH(i)). However, this concept, pot entially important for the development of new treatment strategies for cyto toxic brain edema, has not been validated experimentally. In the present st udy, cell volume and pHi of astrocytes were measured simultaneously in vitr o. Exposure of suspended astrocytes to levels of acidosis found in vivo dur ing ischemia and trauma (pH 6.8-6.2) led to a maximal increase in cell volu me of 121.2% after 60 min (n = 5, p < 0.05) and to immediate intracellular acidification close to extracellular levels (pH 6.2, n = 5, p < 0.05). Inhi bition of membrane transporters responsible for pHi regulation (0.1 mM amil oride for the Na+/H+ antiporter or 1 mM SITS for HCO3--dependent transporte rs) inhibited cell swelling from acidosis but did not affect the profound i ntracellular acidification. In addition, acidosis-induced cell swelling and intracellular acidification were partly prevented by the addition of ZnCl2 (0.1 mM), an inhibitor of selective proton channels not yet described in a strocytes (n = 5, p < 0.05). In conclusion, these data demonstrate that gli al swelling from acidosis is not a cellular response to defend the normal P Hi, as had been thought. If these results obtained in vitro are transferabl e to in vivo conditions, the development of blood-brain barrier-permeable a gents for the inhibition of acidosis-induced cytotoxic edema might be thera peutically useful, since they do not enhance intracellular acidosis and thu s cell damage.