Clearance of cerebrospinal fluid from the sacral spine through lymphatic vessels

Abstract

The pathways of circulation and clearance of cerebrospinal fluid (CSF) in the spine have yet to be elucidated. We have recently shown with dynamic in vivo imaging that routes of outflow of CSF in mice occur along cranial nerves to extracranial lymphatic vessels. Here, we use near-infrared and magnetic resonance imaging to demonstrate the flow of CSF tracers within the spinal column and reveal the major spinal pathways for outflow to lymphatic vessels in mice. We found that after intraventricular injection, a spread of CSF tracers occurs within both the central canal and the spinal subarachnoid space toward the caudal end of the spine. Outflow of CSF tracers from the spinal subarachnoid space occurred predominantly from intravertebral regions of the sacral spine to lymphatic vessels, leading to sacral and iliac LNs. Clearance of CSF from the spine to lymphatic vessels may have significance for many conditions, including multiple sclerosis and spinal cord injury.

Meningeal lymphatic vessels regulate brain tumor drainage and immunity

“…In contrast to the above findings that were obtained with the MLVs located at the dorsal part of the skull, 7,8 several recent studies support the role of the basal MLVs in drainage of fluid from the CNS. [14][15][16] Consistently, a very recent study showed that the MLVs located at the basal part of the skull appeared to be morphologically distinct and have stronger draining functions than dorsal MLVs. 11 Therefore, the structural and functional relationships and interdependence of these MLVs need to be further investigated.…”

“…11,14,44 Along this line, some studies using tracer infusion indicated that basal MLVs are the major pathway for CSF outflow. [14][15][16] Furthermore, a very recent report showed a reduction in lymphatic outflow of CSF in GL261 glioma model. 46 In this study, we also found that basal MLVs underwent remodeling and exhibited tumor cell invasion (Supplementary information, Figs.…”

Meningeal lymphatic network: The middleman of neuroinflammation

“…LV can be found not only in the brain meninges, but also in the spinal cord meninges ( Figure 1). 24,25 The different sections of the spinal cord lymphatics will drain into different lymph nodes corresponding to the spinal region: the cervical region appears to drain into the cervical lymph nodes, the thoracic lymphatic into the mediastinal lymph nodes, whereas the lumbar lymphatic drain into the renal and lumbar lymph nodes. 8 Instead of running along veins, they appear to be localized around each nerve root.…”

“…8,23 In the spinal cord region, the LV harbor an initial lymphatic phenotype that suggests they have a capacity to drain the surrounding CSF and interstitial fluid. 24,25 Although we are elucidating the anatomical complexity of the meningeal lymphatic network from the brain to the spinal cord, further studies are necessary to understand the potential regional specificity and their contribution to pathological conditions. 8,24 Recent light sheet microscopy and functional studies have shown the complex architecture of the spinal cord lymphatics and their connection to the peripheral lymph nodes.…”

“…24,25 The different sections of the spinal cord lymphatics will drain into different lymph nodes corresponding to the spinal region: the cervical region appears to drain into the cervical lymph nodes, the thoracic lymphatic into the mediastinal lymph nodes, whereas the lumbar lymphatic drain into the renal and lumbar lymph nodes. 24,25 Although we are elucidating the anatomical complexity of the meningeal lymphatic network from the brain to the spinal cord, further studies are necessary to understand the potential regional specificity and their contribution to pathological conditions. Indeed, it has been shown that the dorsal and the basal meningeal lymphatic are differentially responding to normal aging and growth factor deprivation.…”