IS GLIA DYSFUNCTION THE INITIAL CAUSE OF NEURONAL DEATH IN ISCHEMIC PENUMBRA

The supportive role of glial cells on neuronal function and survival h as been studied in anesthetized rats by using the selective gliotoxin fluorocitrate. Disabling glia operation reproduced many features of is chemic penumbra. An initial mild acidosis and increased interstitial p otassium but not glutamate was followed after 3-4 h by repetitive spre ading depression waves. These gradually provoked higher levels of acid osis, potassium and glutamate, gradual neuronal function decay and fin ally, 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 pathol ogy.