Neural progenitor cells resist excitatory amino acid-induced neurotoxicity

The applications of neural progenitor cells in clinical therapy for neural degeneration, such as Parkinson's disease, Huntington's disease, and cerebral infarction, have long been explored widely. It had been suggested that these cells may block the apoptosis of ischemia-induced neuronal damage and may themselves resist neurotoxic factors. In the present study, neural progenitor cells derived from the cortex of rodent embryos were cultured with the mitogenic agent epidermal growth factor. It was observed that these progenitor cells could self-renew and differentiate into a number of types of neurons and glial cells. By using sodium nitroprusside, glutamate, and N-methyl-D-aspartate, these neural progenitor cells were shown to have a higher resistance to neurotoxicity induced by these drugs compared with primary neuronal cells. However, the release of nitric oxide in response to glutamate by these neural progenitor cells was similar to the released by primary neuronal cells. Also, when the glutamate-stimulated increase in intracellular free Ca(2+) concentration was measured, stimulation of the glutamate receptors could not induce a significant influx of Ca(2+) into these progenitor cells until they differentiated. Our results suggest that the resistance of neural progenitor cells to neurotoxicity may be partially due to a lack of response to glutamate. In addition, some progenitor-generated neurotrophic factors may contribute to the resistance of these cells to nitric oxide-induced neurotoxicity.