Is glia disfunction the initial cause of neuronal death in ischemic penumbra?

The supportive role of glial cells on neuronal function and survival has been studied in anesthetized rats by using the selective gliotoxin fluorocitrate. Disabling glia operation reproduced many features of ischemic penumbra. An initial mild acidosis and increased interstitial potassium but not glutamate was followed after 3-4 h by repetitive spreading depression waves. These gradually provoked higher levels of acidosis, potassium and glutamate, gradual neuronal function decay and finally, neuron death. We conclude that neurons become highly vulnerable to spreading depression waves only in absence of normal glia operation. Our findings directly associate early glial disfunction to neuronal loss and lead to new insights for the understanding of ischemic pathology.