Damisah Eyiyemisi C, Hill Robert A, Tong Lei, Murray Katie N, Grutzendler Jaime
Department of Neurology, Yale School of Medicine, New Haven, Connecticut, USA.
Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut, USA.
Nat Neurosci. 2017 Jul;20(7):1023-1032. doi: 10.1038/nn.4564. Epub 2017 May 15.
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.
周细胞和平滑肌细胞是脑微血管的重要组成部分。然而，目前尚无明确鉴定这些细胞类型的技术，这极大地限制了它们在体内的研究。在此，我们表明荧光尼氏染料NeuroTrace 500/525能特异性标记脑周细胞，从而在活体小鼠中实现高分辨率光学成像。我们证明毛细血管周细胞是一类具有独特形态、分子和功能特征的壁细胞，与表达前毛细血管或小动脉平滑肌肌动蛋白的细胞并不重叠。染料摄取的显著特异性表明周细胞具有其他脑细胞所没有的分子转运机制。我们证明了在微血管发育、衰老过程中以及脑缺血和阿尔茨海默病模型中对周细胞进行纵向成像的可行性。在任何小鼠模型中轻松标记周细胞的能力为广泛研究血管发育、神经血管耦合和神经病理学中的壁细胞开辟了可能性。
