Spreading depression and delayed neuronal death

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Spreading depression (SD) in a flow-restricted area of the brain may be prolonged and may become potentially harmful by releasing glutamate. We induced SD in an oligemia model and examined the subsequent glutamate release. In 18 anesthetized male Fischer rats, a laser Doppler flowmeter, an electroenzymatic electrode and microdialysis probe for continuous measurement of glutamate and amino acid assay respectively. And a calomel electrode for measuring DC potential were placed through a cranial window positioned 3 mm away from a second window where KCl-soaked cotton was placed to initiate SD.The left carotid artery or both the common carotid arteries were ligated to suppress reactive hyperemia of SD.SD produced an increase in glutamate from 24.8*13.8 to 33.5*25.3 muM (peak value)(P<0.0001). After ligation of both carotid arteries, the duration of SD increased from 1.5*0.6 mm (before ligation) to 6.4*5.1 mm (P<0.05). Glutamate reached a peak level of 63.9*72.3 muM, then quickly returned to the control value. The dialysate glutamate concentrations were 0.55*0.09, 0.25*0.19, 0.49*0.28 and 0.74*0.48 muM under the control, SD, SD induced after bilateral carotid ligation and reperfusion conditions, respectively. The dialysate glutamate concentrations of the 4 animals that developed AD increased significantly to 2.7*2.4 muM (P<O.05 compared with the control value) and continued to increase after reperfusion to 3.7*1.6 muM (p<O.O5 compared with the control value). The glutamate concentrations did not differ even after SD induction with hypoperfusion (all p>O.O5 cf control), whereas anoxic depolarization caused significantly high glutamate release. It is concluded that prolonged SD is not accompanied by a progressive increase in glutamate. Therefore, glutamate release induced by SD may not exert harmful effects on neurons.