Hypoxic neuronal injury in vitro depends on extracellular glutamine

Hypoxic neuronal injury (HNI) in cortical cell cultures was enhanced in a concentration-dependent fashion by the presence of 500 μM to 2 mM (EC₅₀ about 500 μM) glutamine in the medium, concentrations approximating those normally present in cerebrospinal fluid (CSF). Regardless of the glutamine concentration, glutamate receptor antagonists 2-amino-5-phosphonovalerate or dextrorphan could substantially reduce HNI. Thus, the availability of extracellular glutamine could be a determinant of hypoxic neuronal injury in vivo, most likely reflecting its importance in the synthesis of the neurotransmitter excitotoxins glutamate and aspartate.