Glutamate metabolism in the injured spinal cord

Glutamate is used in the central nervous system (CNS) as an excitatory neurotransmitter, as a precursor for gamma-aminobutyric acid (GABA), and as a carbon source for energy production. Glutamate levels are maintained in the CNS in a ôglutamine cycleö by the neuronal enzyme, glutaminase (GT), and the astrocytic enzyme, glutamine synthetase (GS). Following trauma to the CNS, glutamate is released acutely in large amounts. Chronically, reactive astrocytosis and reorganization of glutamatergic and GABAergic pathways occur. Following spinal transection in the rat, reactive astrocytes in the white and gray matter have increased mRNA for GS within hours and have increased GS immunoreactivity and/or enzyme activity which lasts for weeks. Decreased GT enzyme activity occurs several days following spinal transection, predominantly in the gray matter. These changes in GS and GT lead to altered levels of glutamate and glutamine in the white and gray matter both rostral and caudal to the injury site. The altered glutamate metabolism in the spinal cord may contribute to nervous tissue reorganization and to pathophysiological conditions following spinal cord injury.