Despite the possible role of impaired cerebral tissue oxygenation in age-related cognition decline, much is still unknown about the changes in brain tissue pO2 with age. Using a detailed investigation of the age-related changes in cerebral tissue oxygenation in the barrel cortex of healthy, awake aged mice, we demonstrate decreased arteriolar and tissue pO2 with age. These changes are exacerbated after middle-age. We further uncovered evidence of the presence of hypoxic micro-pockets in the cortex of awake old mice. Our data suggests that from young to middle-age, a well-regulated capillary oxygen supply maintains the oxygen availability in cerebral tissue, despite decreased tissue pO2 next to arterioles. After middle-age, due to decreased hematocrit, reduced capillary density and higher capillary transit time heterogeneity, the capillary network fails to compensate for larger decreases in arterial pO2. The substantial decrease in brain tissue pO2, and the presence of hypoxic micro-pockets after middle-age are of significant importance, as these factors may be related to cognitive decline in elderly people.

Neurovascular coupling (NVC) underlying the local increase in blood flow during neural activity forms the basis of functional brain imaging and is altered in epilepsy. Because astrocytic calcium (Ca) signaling is involved in NVC, this study investigates the role of this pathway in epilepsy. Here, we exploit 4-AP induced epileptic events to show that absolute Ca concentration in cortical astrocyte endfeet in vivo correlates with the diameter of precapillary arterioles during neural activity. We simultaneously monitored free Ca concentration in astrocytic endfeet with the Ca-sensitive indicator OGB-1 and diameter of adjacent arterioles in the somatosensory cortex of adult mice by two-photon fluorescence lifetime measurements following 4-AP injection. Our results reveal that, regardless of the mechanism by which astrocytic endfoot Ca was elevated during epileptic events, increases in Ca associated with vasodilation for each individual ictal event in the focus. In the remote area, increases in Ca correlated with vasoconstriction at the onset of seizure and vasodilation during the later part of the seizure. Furthermore, a slow increase in absolute Ca with time following multiple seizures was observed, which in turn, correlated with a trend of arteriolar constriction both at the epileptic focus and remote areas.

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