Center for Translational Neuromedicine, Division of Glial Disease and Therapeutics, University of Rochester, Rochester, NY, USA.
Department of Mechanical Engineering, University of Rochester, Rochester, NY, USA.
Nat Aging. 2024 Oct;4(10):1418-1431. doi: 10.1038/s43587-024-00691-3. Epub 2024 Aug 15.
Cervical lymphatic vessels (cLVs) have been shown to drain solutes and cerebrospinal fluid (CSF) from the brain. However, their hydrodynamical properties have never been evaluated in vivo. Here, we developed two-photon optical imaging with particle tracking in vivo of CSF tracers (2P-OPTIC) in superficial and deep cLVs of mice, characterizing their flow and showing that the major driver is intrinsic pumping by contraction of the lymphatic vessel wall. Moreover, contraction frequency and flow velocity were reduced in aged mice, which coincided with a reduction in smooth muscle actin expression. Slowed flow in aged mice was rescued using topical application of prostaglandin F, a prostanoid that increases smooth muscle contractility, which restored lymphatic function in aged mice and enhanced central nervous system clearance. We show that cLVs are important regulators of CSF drainage and that restoring their function is an effective therapy for improving clearance in aging.
颈淋巴导管（cLVs）已被证明可从大脑中排出溶质和脑脊液（CSF）。然而，它们的流体动力学特性从未在体内进行过评估。在这里，我们开发了用于浅层和深层小鼠 cLVs 的双光子光学成像与粒子示踪技术（2P-OPTIC），对其流动进行了特征描述，并表明主要驱动力是淋巴管壁收缩引起的内在泵送作用。此外，在老年小鼠中，收缩频率和流速降低，这与平滑肌肌动蛋白表达减少相一致。通过局部应用前列腺素 F（一种增加平滑肌收缩性的前列腺素）来减缓老年小鼠的流速，可恢复其淋巴功能，并增强中枢神经系统清除率。我们表明 cLVs 是 CSF 引流的重要调节因子，恢复其功能是改善衰老时清除率的有效治疗方法。
