Real-time monitoring of ischemic and contralateral brain pO2 during stroke by variable length multisite resonators

Abstract

Purpose Electron paramagnetic resonance (EPR) oximetry using variable length multi-probe implantable resonator (IR), was used to investigate the temporal changes in the ischemic and contralateral brain pO2 during stroke in rats. Material and Methods The EPR signal to noise ratio (S/N) of the IR with four sensor loops at a depth of up to11 mm were compared with direct implantation of lithium phthalocyanine (LiPc, oximetry probe) deposits in vitro. These IRs were used to follow the temporal changes in pO2 at two sites in each hemisphere during ischemia induced by left middle cerebral artery occlusion (MCAO) in rats breathing 30% O2 or 100% O2. Results The S/N ratios of the IRs were significantly greater than the LiPc deposits. A similar pO2 at two sites in each hemisphere prior to the onset of ischemia was observed in rats breathing 30% O2. However, a significant decline in the pO2 of the left cortex and striatum occurred during ischemia but no change in the pO2 of the contralateral brain was observed. A significant increase in the pO2 of only the contralateral non-ischemic brain was observed in the rats breathing 100% O2. No significant difference in the infarct volume was evident between the animals breathing 30% O2 or 100% O2 during ischemia. Conclusions EPR oximetry with IRs can repeatedly assess temporal changes in the brain pO2 at four sites simultaneously during stroke. This oximetry approach can be used to test and develop interventions to rescue ischemic tissue by modulating cerebral pO2 during stroke.

Multi-modal assessment of neurovascular coupling during cerebral ischaemia and reperfusion using remote middle cerebral artery occlusion

“…The remote MCAO model leads to changes in CBF and brain oxygenation consistent with the conventional intraluminal filament MCAO model. 22 We showed here that evoked CBF responses were diminished during ischaemia compared with pre-MCAO, alongside attenuated evoked tpO 2 , CMRO 2 and neuronal activity. Upon reperfusion, while evoked excitatory neuronal activity recovered, there was only partial restoration of evoked CBF and CMRO 2 indicative of disrupted neurovascular coupling.…”

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

“…We have previously reported the effect of breathing hypoxic (10-15% O 2 ) and hyperoxic (100% O 2 , carbogen and hyperbaric oxygen therapy) challenges on the brain pO 2 in rats and rabbits with the goal to understand the sensitivity of IRs to local changes of brain pO 2 and how improved oxygen levels protect brain from ischemic stroke in the brain [28,29,32,33]. …”

“…The entire resonator was coated with a gas-permeable and biocompatible Teflon AF2400 [38]. The implantable resonators are well tolerated by the animals (mice, rats, or rabbits) [32, 39-42]. The mean area of the oximetry probe at the surface of each sensor loop was 1.3 - 1.6 mm 2 .…”

“…However, these studies have also indicated the areas in which progress is needed, particularly the need for technological developments that can enable measurements in tissues at depths of greater than 10 mm. We have developed EPR oximetry using implantable oxygen sensors to repeatedly measure cerebral pO 2 in the regions directly affected by ischemic stroke as well as the contralateral regions of the rat brain [32]. We have also systematically developed sensors that can be used to assess pO 2 at depths greater than 10 mm from the surface [33].…”

In vivo electron paramagnetic resonance oximetry and applications in the brain

“…Therefore, the potential that NBO is a viable neuroprotective strategy for acute ischemic stroke is compelling 4. Furthermore, if two LiPc crystals are implanted in the ischemic core and the contralateral hemisphere respectively, the pO 2 can be followed at both the ischemic and non-ischemic (contralateral) sides simultaneously,84 and more recently, an implantable resonator with multiple sensor loops loaded with LiPc at varying depths and positions allow for multisite determination of cerebral pO 2 at depths > 1 cm by EPR 747585…”