The Role of Organic Osmolytes in the Response of Cultured Astrocytes to Hyperosmolarity

Abstract

Idiogenic osmoles are volume-regulatory organic solutes that accumulate within a cell in response to hyperosmolar conditions such as those found in diabetic ketoacidosis or hypernatremic dehydration in infants. Intracellular metabolites known to play this role include certain amino acids and taurine, polyols, and trimethylamines. In this study, in vitro astrocyte cultures prepared from the cerebral cortices of 1-day-old Sprague-Dawley rats were exposed to graded conditions of hypernatremia (325-375 mOsm/kg), a range that can be observed in vivo, for 24, 48, and 72 hours. Cell survival and generation of idiogenic osmoles were determined. Next, we assessed the ability of selected exogenous osmoles to protect the cultured cells from the effects of hypernatremia. Significant cell loss occurred after 48 to 72 hours of exposure and was proportional to the degree of hyperosmolarity. Addition of myoinositol (1 mM) to the cultures reduced cell loss resulting from hypernatremia by approximately 50%. In agreement with previous studies, intracellular levels of myoinositol and taurine correlated with the degree of in vitro hypernatremic exposure and play a significant role in increasing survival of astrocytes subjected to hypertonic insult.