Abstract
To study the potentially different roles of the excitatory amino acids glutamate and aspartate in the development of ischemic injury of the spinal cord, we measured their release from cultured neurons and glial cells under ischemic conditions. We also examined changes in intracellular Ca^2+^ concentration and the damage elicited in cultured neurons by glutamate and aspartate. Hypoxicβhypoglycemic treatment (in vitro ischemia) elicited a rapid release of the excitatory amino acids from cultured spinal cord neurons and glial cells, but the release was greater from glial cells than from neurons. The ischemiaβinduced glutamate release from glial cells was transient: the aspartate release lasted longer, although the peak level was smaller than that of glutamate. In cultured neurons, a remarkable elevation in intracellular Ca^2+^ concentration was induced by glutamate but not by a lower concentration (10 ΞΌ__M__) of aspartate, which is below the neurotoxic dose. At the higher concentration (100 ΞΌ__M__), both excitatory amino acids induced a marked elevation in intracellular Ca^2+^ concentration and neuronal death. These results indicate that aspartate is less potent than glutamate in eliciting excitatory neurotransmission under normal physiological conditions. However, under pathological conditions such as ischemia, the increased release of aspartate from glial cells may add to the damage to neighboring neurons.