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Updated: Jan 21, 2026
Two-vessel Occlusion Mouse Model of Cerebral Ischemia-reperfusion
Published on: March 1, 2019
Improvement in Microregional Oxygen Supply/Consumption Balance and Infarct Size After Cerebral Ischemia-Reperfusion
Harvey R Weiss1, Scott J Mellender1, Geza K Kiss1
1Rutgers Robert Wood Johnson Medical School, Neuroscience & Cell Biology, Piscataway, New Jersey.
Background:
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.
Methods:
This was tested in isoflurane-anesthetized rats with middle cerebral artery blockade for 1 hour and reperfusion for 2 hours with or without PF-4708671 (S6K1 inhibitor, 75 mg/kg, 15 minutes 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.
Results:
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 (23 of 80 veins with O2 saturation below 45%). PF-4708671 did not significantly alter cerebral blood flow or O2 consumption. However, it significantly reduced the number of small veins with low O2 saturations in the reperfused region (6 of 80 veins with O2 saturation below 45%). This was associated with a significantly reduced cortical infarct size after S6K1 inhibition (12.9 ± .8% control versus 6.6 ± .3% PF-4708671).
Conclusion:
This suggests that S6K1 inhibition is important for cell survival and that it reduces the number of small microregions with reduced local oxygen balance after cerebral ischemia-reperfusion.
Insights
Inhibition of p70 ribosomal S6 kinase (S6K1) reduces infarct size after cerebral ischemia-reperfusion. S6K1 inhibition improves microregional oxygen balance and enhances cell survival in affected brain tissue.
Area of Science:
- Neuroscience
- Cardiovascular Research
- Biochemistry
Background:
- Cerebral ischemia-reperfusion injury leads to significant brain damage.
- Understanding mechanisms to reduce infarct size is crucial for neuroprotection.
- p70 ribosomal S6 kinase (S6K1) is a potential therapeutic target.
Purpose of the Study:
- To investigate if inhibiting S6K1 reduces infarct size after cerebral ischemia-reperfusion.
- To assess the effect of S6K1 inhibition on microregional oxygen supply/consumption balance.
- To evaluate the impact of S6K1 inhibition on cell survival in ischemic brain tissue.
Main Methods:
- Rats underwent middle cerebral artery blockade followed by reperfusion.
- The S6K1 inhibitor PF-4708671 was administered.
- Regional cerebral blood flow, oxygen consumption, and microregional oxygen saturations were measured.
Main Results:
- S6K1 inhibition did not alter overall cerebral blood flow or oxygen consumption.
- PF-4708671 significantly reduced the number of small veins with low oxygen saturation in the reperfused cortex.
- Cortical infarct size was significantly reduced by approximately 50% in the PF-4708671 treated group.
Conclusions:
- S6K1 inhibition is a promising strategy for reducing infarct size in cerebral ischemia-reperfusion.
- Inhibition of S6K1 improves microregional oxygen balance, contributing to neuroprotection.
- S6K1 inhibition appears to be important for cell survival following ischemic events.
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