Brain Tissue Oxygen Dynamics Under Localised Hypoxia in the Awake State and the Physical Neuroprotective Effects of General Anaesthesia.

Brain health directly depends on maintaining a level of tissue oxygen that is high enough to avoid global hypoxia and local brain ischaemia. It is well documented that general anaesthesia has an anti-hypoxic neuroprotective effect. Previous studies of this effect primarily assessed the biochemical actions of anaesthetics. Physical actions were not well studied because the quantification of oxygen dynamics has only recently been described. Based on known oxygen, blood, and neuronal measurements, under various anaesthesia protocols and in the awake state, we mathematically analysed physical anaesthesia effects on oxygen distribution for localised hypoxia. From this, we built a universal equation of oxygen dynamics which can be applied to both animal and human subjects in awake and anaesthetised states, under normoxia, hyperoxia, and hypoxia. Using this equation, we determined that a proper anaesthesia protocol can protect up to 167 mm3 of local hypoxic cortical brain tissue via oxygen diffusion from healthy neighbouring areas.

Brain Tissue Oxygen and BOLD fMRI Under Different Levels of Neuronal Activity.

Localized increases in neuronal activity are supported by the hemodynamic response, which delivers oxygen to the brain tissue to support synaptic functions, action potentials and other neuronal processes. However, it remains unknown if changes in baseline neuronal activity, which are expected to reflect neuronal metabolic demand, alter the relationship between the local hemodynamic and oxygen behaviour. In order to better characterize this system, we examine here the relationship between brain tissue oxygen (PO2) and hemodynamic responses (BOLD functional MRI) under different levels of neuronal activity. By comparing the stimulus-evoked responses during different levels of baseline neuronal activity, the awake state vs isoflurane anesthesia, we were able to measure how a known change in neuronal demand affected tissue PO2 as well as the hemodynamic response to stimulation. We observed a high correlation between stimulus-evoked PO2 and BOLD responses in the awake state. Moreover, we found that the evoked PO2 and BOLD responses were still present despite the elevated tissue oxygen baseline and decreased baseline of neuronal activity under low concentration isoflurane, and that the magnitudes of these responses decreased by similar proportions but the relationship between these signals was distorted. Our findings point to distortion of the BOLD-PO2 relationship due to anesthesia. The feedback mechanism to adjust the level of brain tissue oxygen, as well as the correlation between BOLD and PO2 responses, are impaired even by a small dose of anesthetics.