Effects of lactic acid on astrocytes in primary culture

Excessive tissue lactic acidosis is considered to be detrimental to the central nervous system (CNS) and may adversely affect recovery from anoxia, ischemia, trauma and epilepsy. Since astrocytes are believed to play a role in pH regulation in the CNS, we studied the effect of this acid on primary astrocyte cultures. Cells exposed to lactic acid showed chromatin clumping, an increase of lipid and dense bodies, a loss of polyribosomal clusters, slightly increased cytoplasmic lucency, swollen mitochondria and tangled intermediate filaments. These alterations progressed with lower pH and longer exposure. Irreversible changes occurred one to two hours after exposure at pH 6; after 30 to 60 minutes (min) at pH 5.5 and after ten to 30 min at pH 5. Comparable results were obtained with the use of other weak acids indicating that the observed changes were due to increased hydrogen ion concentration rather than secondary to lactate per se. Additionally, various concentrations of lactic acid adjusted to identical pH produced similar morphologic alterations. Thus, while lactic acid caused marked and at times irreversible alterations in astrocytes, severe and prolonged acidosis was required to produce such injurious effects. This relative resistance of astrocytes to acidosis is in keeping with their potential role in pH regulation in brain.