SUSCEPTIBILITY OF HIPPOCAMPAL AND CORTICAL-NEURONS TO ARGON-MEDIATED IN-VITRO ISCHEMIA

Neurons from cerebral cortex and hippocampal CA1 sector exhibit a stri king difference in vulnerability to transient ischemia. To establish w hether this difference is due to the inherent (pathoclitic) properties of these neurons, the ischemic susceptibility was studied in primary cortical and hippocampal cultures by using a new model of argon-induce d in vitro ischemia. Neuronal cultures were exposed at 37 degrees C fo r 10-30 min to argon-equilibrated glucose-free medium. During argon eq uilibration, PO2 declined to <2.5 torr within 1 min and stabilized sho rtly later at similar to 1.3 torr. After 30 min of in vitro ischemia, total adenylate was <45% and ATP content <15% of control in both types of culture. Cytosolic calcium activity increased from 15 to 50 nM. Re oxygenation of cultures after in vitro ischemia led to delayed neurona l death, the severity of which depended on the duration of in vitro is chemia but not on the type of neuronal cultures. Energy charge of aden ylate transiently returned to similar to 90% of control after 3 h, but ATP content recovered only to 40% and protein synthesis to <35%. Cyto solic calcium activity continued to rise after ischemia and reached va lues of similar to 500 nM after 3 h, The new argon-induced in vitro is chemia model offers major advantages over previous methods, but despit e this improvement it was not possible to replicate the differences in cortical and hippocampal vulnerability observed in vivo. Our study do es not support the hypothesis that selective vulnerability is due to a n inherent pathoclitic hypersensitivity.