Mechanisms of Glial Swelling from Lactacidosis and High K⁺ Levels in the Extracellular Compartment

Abstract

An important manifestation of ischemic brain edema is swelling of glial cells and dendrites, i.e., cytotoxic brain edema [1,10].The underlying mechanisms resulting in ischemic brain edema are far from understood. This may be attributable to the fact that in ischemia a multitude of processes becomes simultaneously activated in a particularly complex tissue. Therefore, assessment of molecular mechanisms underlying ischemic cell swelling and cell damage is rather difficult. Acidosis and accumulation of K⁺ ions in the extracellular compartment are regularly observed in cerebral ischemia. These factors may lead to cytotoxic brain edema and, eventually, damage to astrocytes and neurons. It has been shown that in cerebral ischemia the extracellular pH can fall to pH 6.0 and below, and that lactic acid accumulates to a level of 20–30 μmol/g [11,16]. Simultaneously, interstitial potassium concentrations in cerebral cortex may rise to 80 mM [16].