Inhibition of p70 ribosomal S6 kinase (S6K1) reduces infarct size without improving microregional oxygen supply/consumption balance after cerebral ischemia‐reperfusion

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We tested the hypothesis that inhibition of p70 ribosomal S6 kinase (S6K1) would decrease infarct size and improve microregional O2 supply/consumption balance after cerebral ischemia‐reperfusion. This was tested in isoflurane anesthetized rats with middle cerebral artery blockade for 1 hr and reperfusion for 2 hr with or without PF‐4708671 (S6K1 inhibitor, 75 mg/kg, 15 min after blockade). 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. There were no significant hemodynamic or arterial blood gas differences between groups. The control ischemic‐reperfused cortex had a similar O2 consumption 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 (48 of 80 veins with O2 saturation below 50%). PF‐4708671 did not significantly alter cerebral blood flow or O2 consumption. It also did not affect O2 supply/consumption balance in the reperfused area (41 of 80 veins with O2 saturation below 50%). However, this was associated with a significantly reduced cortical infarct size after S6K1 inhibition (12.9 ± 0.8% control vs 6.6 ± 0.3% PF‐4708671). This suggests that S6K1 inhibition is important for cell survival, but does not significantly improve local oxygen balance after cerebral ischemia‐reperfusion.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.