"So our discovery may have resulted from the fact that our oligodendrocyte cultures were older than those that had been studied previously," Goldberg says. "Or it may have been due to the fact that they were cultured with astrocytes and therefore behaved more like they do in the brain."
To mimic the conditions that follow stroke, Goldberg and McDonald transiently deprived cultured oligodendrocytes of oxygen and glucose. The treatment caused widespread oligodendrocyte death, which again was attenuated by an AMPA antagonist.
Damage to the living brain
To see what happens in the living brain, the researchers injected AMPA into precisely located portions of white matter in rats. An NMDA antagonist also was included. After 24 hours, only 40 percent of the oligodendrocytes in these regions had survived. In contrast, there was little oligodendrocyte death in rats that received only the NMDA antagonist. The same was true for rats that received only NMDA, though this compound killed overlying neurons. The researchers then showed that oligodendrocytes really do express AMPA receptors while they are still in living animals. Recent experiments in which rats suffered traumatic spinal cord injury or stroke have produced the same results.
"The fact that these receptors are expressed and can lead to the death of cells
suggests that maybe excitotoxicity of AMPA/kainate receptors is the mechanism of
injury in disease states such as head injury and stroke," Goldberg says.
"It also may end up being a very
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Contact: Linda Sage
sage@medicine.wustl.edu
314-286-0119
Washington University in St. Louis
10-Apr-1998