Astrocytic GPCR-Induced Ca Signaling Is Not Causally Related to Local Cerebral Blood Flow Changes.

Activation of Gq-type G protein-coupled receptors (GPCRs) gives rise to large cytosolic Ca elevations in astrocytes. Previous in vitro and in vivo studies have indicated that astrocytic Ca elevations are closely associated with diameter changes in the nearby blood vessels, which astrocytes enwrap with their endfeet. However, the causal relationship between astrocytic Ca elevations and blood vessel diameter changes has been questioned, as mice with diminished astrocytic Ca signaling show normal sensory hyperemia.

Virally induced CRISPR/Cas9-based knock-in of fluorescent albumin allows long-term visualization of cerebral circulation in infant and adult mice.

Albumin, a protein produced by liver hepatocytes, represents the most abundant protein in blood plasma. We have previously engineered a liver-targeting adeno-associated viral vector (AAV) that expresses fluorescent protein-tagged albumin to visualize blood plasma in mice. While this approach is versatile for imaging in adult mice, transgene expression vanishes when AAV is administered in neonates due to dilution of the episomal AAV genome in the rapidly growing liver.

Liver-secreted fluorescent blood plasma markers enable chronic imaging of the microcirculation.

Studying blood microcirculation is vital for gaining insights into vascular diseases. Blood flow imaging in deep tissue is currently achieved by acute administration of fluorescent dyes in the blood plasma. This is an invasive process, and the plasma fluorescence decreases within an hour of administration.