Threshold of ischemic depolarization for neuronal injury following four-vessel occlusion in the rat cortex

Previous studies have indicated that prolonging the onset of ischemic depolarization reduces neuronal damage. However, the relationship between the duration of ischemic depolarization and its histological outcome has not been quantitatively evaluated. Rats were anesthetized (with 1% halothane), intubated, and placed in a stereotaxic frame. Direct current (DC)-potential in the 5th layer of the parietal cortex was measured. Changes in cerebral blood flow (CBF) were monitored by a laser-Doppler flow probe placed adjacent to the DC-electrode. Animals were subjected to four-vessel occlusion for 5 minutes, 10 minutes, or 20 minutes. The histological outcome was evaluated at the DC-recorded site 7 days after the insult. Initiation of ischemia reduced CBF to 9%-28% of the preischemic value. Initial DC-deflection (14+/-3 mV), indicating ischemic depolarization, was observed at 172+/-112 seconds after the onset of ischemia. Total durations of ischemic depolarization were 6.4+/-1.5 minutes, 10.6+/-3.5 minutes and 19.8+/-4.6 minutes in rats in which ischemia was induced for 5 minutes, 10 minutes, and 20 minutes, respectively. The regression curve showed that there was a close relationship between percentage of damaged neurons and duration of ischemic depolarization (r2 = 0.80, P = .001). The durations of ischemic depolarization for neuronal injury in 30%, 50%, and 70% of pyramidal neurons in the parietal cortex were 15.6 minutes (95% confidence interval, 14.2-17.0 minutes), 20.3 minutes (18.5-22.7 minutes) and 25.0 minutes (22.7-28.5 minutes), respectively. It is thought that shortening the duration of ischemic depolarization is a rational approach for reducing the severity of ischemic injury.