Functional recovery of cortical neurons as related to degree and duration of ischemia

Abstract

Imultaneous recordings of spontaneous single cell activity and local cerebral blood flow were obtained from 72 cortical neurons and adjacent brain in 54 cats before, during, and after ischemia induced by reversible occulsion of the middle cerebral artery. In most cells spontaneous electrical activity ceased at flow values of about 0.18 ml/gmm/in (range, 0.06 to 0.22 ml/gm/min). No signal was obtained from 28 neurons during reperfusion following ischemia of varying degree and duration. Overall, neurons exposed to a residual flow of 0.14 ml/gm/min or less for more than 45 minutes had a poorer prognosis compared to any other combination of degree and duration of ischemia. A discriminant curve was estimated to define the border line between recovering and nonrecovering cells. Regions showing irreversible neuronal failure contained selective neuronal necrosis or areas of infarction by histological examination. Reperfusion restored neuronal function in 44 cells. In this group of neurons, there was a joint interaction of duration of ischemia, ischemic residual flow, and recovery time: cells exposed to moderate ischemia (0.09 to 0.22 ml/gm/min) for up to 20 minutes recovered rapidly; most neurons subjected either to extreme ischemia (less than 0.09 ml/gm/min) of short duration (less than 20 minutes) or to moderate ischemia (0.09 to 0.22 ml/gm/min) for longer periods (20 to 141 minutes) required from 19 to 50 minutes for recovery. A few resistant neurons tolerated less than 0.09 ml/gm/min for more than 20 minutes. Cell survival and functional recovery following ischemia depend not only on separate effects of residual flow and duration of ischemia but on their combined influence. Selective vulnerability forms the natural basis of scattered cell survival.