Dynamic EPR Oximetry of Changes in Intracerebral Oxygen Tension During Induced Thromboembolism

Cerebral tissue oxygenation (oxygen tension, pO₂) is a critical parameter that is closely linked to brain metabolism, function, and pathophysiology. In this work, we have used electron paramagnetic resonance oximetry with a deep-tissue multi-site oxygen-sensing probe, called implantable resonator, to monitor temporal changes in cerebral pO₂ simultaneously at four sites in a rabbit model of ischemic stroke induced by embolic clot. The pO₂ values in healthy brain were not significantly different among the four sites measured over a period of 4 weeks. During exposure to 15% O₂ (hypoxia), a sudden and significant decrease in pO₂ was observed in all four sites. On the other hand, brief exposure to breathing carbogen gas (95% O₂ + 5% CO₂) showed a significant increase in the cerebral pO₂ from baseline value. During ischemic stroke, induced by embolic clot in the left brain, a significant decline in the pO₂ of the left cortex (ischemic core) was observed without any change in the contralateral sites. While the pO₂ in the non-infarct regions returned to baseline at 24-h post-stroke, pO₂ in the infarct core was consistently lower compared to the baseline and other regions of the brain. The results demonstrated that electron paramagnetic resonance oximetry with the implantable resonator can repeatedly and simultaneously report temporal changes in cerebral pO₂ at multiple sites. This oximetry approach can be used to develop interventions to rescue hypoxic/ischemic tissue by modulating cerebral pO₂ during hypoxic and stroke injury.