Cerebral tissue pO₂ response to stimulation is preserved with age in awake mice

Compromised oxygen supply to cerebral tissue could be an important mechanism contributing to age-related cognition decline. We recently showed in awake mice that resting cerebral tissue pO₂ decreases with age, a phenomenon that manifests mainly after middle-age. To extend these findings, here we aimed to study how tissue pO₂ response to neuronal stimulation is affected by aging. We used two-photon phosphorescence lifetime microscopy to directly measure the brain tissue pO₂ response to whisker stimulation in healthy awake young, middle-aged and old mice. We show that despite a decrease in baseline tissue pO₂, the amplitude of the tissue pO₂ response to stimulation is well preserved with age. However, the response dynamics are altered towards a slower response with reduced post-stimulus undershoot in older ages, possibly due to stiffer vessel wall among other factors. An estimation of the net oxygen consumption rate using a modified Krogh model suggests that the O₂ overshoot during stimulation may be necessary to secure a higher capillary O₂ delivery to the tissue proportional to increased CMRO₂ to maintain the capillary tissue pO₂. It was observed that the coupling between the CMRO₂ and capillary O₂ delivery is preserved with age.