PT  - JOURNAL ARTICLE
AU  - Robert Fern
AU  - Thomas Möller
TI  - Rapid Ischemic Cell Death in Immature Oligodendrocytes: A Fatal Glutamate Release Feedback Loop
AID  - 10.1523/JNEUROSCI.20-01-00034.2000
DP  - 2000 Jan 01
TA  - The Journal of Neuroscience
PG  - 34--42
VI  - 20
IP  - 1
4099  - http://www.jneurosci.org/content/20/1/34.short
4100  - http://www.jneurosci.org/content/20/1/34.full
SO  - J. Neurosci.2000 Jan 01; 20
AB  - Ischemic injury of immature oligodendrocytes is a major component of the brain injury associated with cerebral palsy, the most common human birth disorder. We now report that cultured immature oligodendrocytes [O4+/galactoceramide (GC)−] are exquisitely sensitive to ischemic injury (80% of cells were dead after 25.5 min of oxygen and glucose withdrawal). This rapid ischemic cell death was mediated by Ca2+ influx via non-NMDA glutamate receptors. The receptors were gated by the release of glutamate from the immature oligodendrocytes themselves via reverse glutamate transport and included a significant element of autologous feedback of glutamate from cells onto their own receptors. High (≥100 μm) extracellular glutamate was protective against ischemic injury as a result of non-NMDA glutamate receptor desensitization. Other potential pathways of Ca2+ influx, such as voltage-gated Ca2+ channels, NMDA receptors, or the Na+–Ca2+ exchanger, did not significantly contribute to ischemic Ca2+ influx or cell injury. Release of Ca2+ from intracellular stores was also not an important factor. In agreement with previous studies, more mature oligodendrocytes (O4−/GC+) were found to be less sensitive to ischemic injury than were the immature cells studied here.