A fluoro-Nissl dye identifies pericytes as distinct vascular mural cells during in vivo brain imaging

No techniques exist for the precise identification of vascular pericytes. Here the authors identify and characterize a fluorescent dye that exclusively labels pericytes. Using this tool for intravital imaging of the mouse brain, the authors provide conclusive evidence that these cells are molecularly and functionally distinct from all other brain and vascular cells. Pericytes and smooth muscle cells are integral components of the brain microvasculature. However, no techniques exist to unambiguously identify these cell types, greatly limiting their investigation in vivo. Here we show that the fluorescent Nissl dye NeuroTrace 500/525 labels brain pericytes with specificity, allowing high-resolution optical imaging in the live mouse. We demonstrate that capillary pericytes are a population of mural cells with distinct morphological, molecular and functional features that do not overlap with precapillary or arteriolar smooth muscle actin-expressing cells. The remarkable specificity for dye uptake suggests that pericytes have molecular transport mechanisms not present in other brain cells. We demonstrate feasibility of longitudinal pericyte imaging during microvascular development and aging and in models of brain ischemia and Alzheimer's disease. The ability to easily label pericytes in any mouse model opens the possibility of a broad range of investigations of mural cells in vascular development, neurovascular coupling and neuropathology.