Kwon Sunkuk, Janssen Christopher F, Velasquez Fred Christian, Sevick-Muraca Eva M
Center for Molecular Imaging, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, United States.
Center for Laboratory Animal Medicine and Care, University of Texas Health Science Center at Houston, Houston, TX 77030, United States.
J Immunol Methods. 2017 Oct;449:37-43. doi: 10.1016/j.jim.2017.06.010. Epub 2017 Jun 22.
Cerebrospinal fluid (CSF) is known to be reabsorbed by the lymphatic vessels and drain into the lymph nodes (LNs) through peripheral lymphatic vessels. In the peripheral lymphatics, the contractile pumping action of lymphangions mediates lymph drainage; yet it is unknown whether lymphatic vessels draining cranial and spinal CSF show similar function. Herein, we used non-invasive near-infrared fluorescence imaging (NIRFI) to image (i) indocyanine green (ICG) distribution along the neuraxis and (ii) routes of ICG-laden CSF outflow into the lymphatics following intrathecal lumbar administration. We demonstrate lymphatic contractile function in peripheral lymphatics draining from the nasal lymphatics to the mandibular LNs. In addition, we observed afferent sciatic lymphatic vessels, which also show contractile activity and transport spinal CSF into the sciatic LNs. This drainage pattern was also visualized by NIRFI following intrathecal thoracic injection. In situ intravital imaging following intrathecal lumbar injection of blue dye shows similar distributions to that seen in vivo with ICG. NIRFI could be used as a tool to probe CSF pathology including neurological disorders by imaging CSF outflow dynamics to lymphatics.
已知脑脊液（CSF）由淋巴管重吸收，并通过外周淋巴管引流至淋巴结（LN）。在外周淋巴管中，淋巴管节段的收缩泵吸作用介导淋巴引流；然而，引流颅部和脊髓脑脊液的淋巴管是否具有类似功能尚不清楚。在此，我们使用非侵入性近红外荧光成像（NIRFI）来成像：（i）吲哚菁绿（ICG）沿神经轴的分布，以及（ii）鞘内腰椎给药后载有ICG的脑脊液流出至淋巴管的途径。我们证明了从鼻淋巴管引流至下颌淋巴结的外周淋巴管具有淋巴收缩功能。此外，我们观察到传入坐骨淋巴管，其也表现出收缩活性，并将脊髓脑脊液输送至坐骨淋巴结。鞘内胸腔注射后，这种引流模式也通过NIRFI可视化。鞘内腰椎注射蓝色染料后的原位活体成像显示出与ICG在体内所见相似的分布。NIRFI可作为一种工具，通过成像脑脊液向淋巴管的流出动力学来探究包括神经系统疾病在内的脑脊液病理学。
