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 O ₂ 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 C ¹⁴ -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 O ₂ consumption, but lower blood flow and higher O ₂ extraction compared to the contralateral cortex. However, microregional O ₂ supply/consumption balance was significantly reduced in the ischemic-reperfused cortex with many areas of low O ₂ saturation (42 of 80 veins with O ₂ saturation below 50%). SC-79 did not significantly affect cerebral O ₂ consumption, but significantly improved O ₂ supply/consumption balance in the reperfused area (18 of 80 veins with O ₂ 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.