Akt activation improves microregional oxygen supply/consumption balance after cerebral ischemia-reperfusion

There have been reports that activation of Akt may provide neuroprotection after cerebral ischemia-reperfusion. We tested the hypothesis that activation of Akt would decrease infarct size and improve microregional O₂ supply/consumption balance after cerebral ischemia-reperfusion. This hypothesis was tested in isoflurane-anesthetized rats with middle cerebral artery blockade for 1 h and reperfusion for 2 h with or without SC-79 (Akt activator, 0.05 mg/kg, three doses). Regional cerebral blood flow was determined using a C¹⁴-iodoantipyrine autoradiographic technique. Regional small vessel (20-60 μm diameter) arterial and venous oxygen saturations were determined microspectrophotometrically. Akt phosphorylation was determined by Western blot. There were no significant hemodynamic or blood gas differences between groups. The control ischemic-reperfused cortex had a similar O₂ consumption, but lower blood flow and higher O₂ extraction compared to the contralateral cortex. However, microregional O₂ supply/consumption balance was significantly reduced in the ischemic-reperfused cortex with many areas of low O₂ saturation (42 of 80 veins with O₂ saturation below 50%). SC-79 did not significantly affect cerebral O₂ consumption, but significantly improved O₂ supply/consumption balance in the reperfused area (18 of 80 veins with O₂ saturation below 50%). This was associated with a reduced cortical infarct size (13.3 ± 0.5% control vs 6.7 ± 0.3% SC-79). In control, Akt phosphorylation was elevated at 2 h after ischemia. With SC-79, Akt was activated at 15 min but not at 2 h in the ischemic reperfused area. These results suggest that early Akt activation is important for not only cell survival, but also for the control of local oxygen balance after cerebral ischemia-reperfusion.