Abstract
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 pO(2) decreases with age, a phenomenon that manifests mainly after middle-age. To extend these findings, here we aimed to study how tissue pO(2) response to neuronal stimulation is affected by aging. We used two-photon phosphorescence lifetime microscopy to directly measure the brain tissue pO(2) response to whisker stimulation in healthy awake young, middle-aged and old mice. We show that despite a decrease in baseline tissue pO(2), the amplitude of the tissue pO(2) 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 O(2) overshoot during stimulation may be necessary to secure a higher capillary O(2) delivery to the tissue proportional to increased CMRO(2) to maintain the capillary tissue pO(2). It was observed that the coupling between the CMRO(2) and capillary O(2) delivery is preserved with age.