The anatomy and metabolome of the lymphatic system in the brain in health and disease

Abstract

Recent studies have demonstrated that the brain is equipped with a lymphatic drainage system that is actively involved in parenchymal waste clearance, brain homeostasis and immune regulation. However, the exact anatomic drainage routes of brain lymph fluid (BLF) remain elusive, hampering the physiological study and clinical application of this system. In this study, we systematically dissected the anatomy of the BLF pathways in a rat model. Moreover, we developed a protocol to collect BLF from the afferent lymphatic vessels of deep cervical lymph nodes (dcLNs) and cerebrospinal fluid (CSF) from the fourth ventricle. Nuclear magnetic resonance spectroscopy showed that BLF contains more metabolites than CSF, suggesting that BLF might be a more sensitive indicator of brain dynamics under physiological and pathological conditions. Finally, we identified several metabolites as potential diagnostic biomarkers for glioma, Parkinson's disease and CNS infectious diseases. Together, these data may provide insight into the physiology of the lymphatic system in the brain and into the clinical diagnosis of CNS disorders.

Strategies to package recombinant Adeno-Associated Virus expressing the N-terminal gasdermin domain for tumor treatment

“…All rats were purchased from the Experimental Animal Center of Huazhong Agricultural University. In order to construct a GBM rat model, C6-luc cells (1 × 10 6 ) in 10 μl of F-12K medium were stereotactically injected into the left striatum of Wistar male rats (180–220 g) 34 .…”

Brain Barriers and brain fluids research in 2020 and the fluids and barriers of the CNS thematic series on advances in in vitro modeling of the blood–brain barrier and neurovascular unit

“…He et al [79] have developed an interesting approach for sampling brain lymph fluid from the afferent lymph vessels of deep cervical lymph nodes. A different analyte profile may result from this fluid compared to the CSF sampled from the usual sites (e.g., lumbar puncture).…”

Impediment of Cerebrospinal Fluid Drainage Through Glymphatic System in Glioma

“…Recent studies have confirmed three outflow pathways of CSF in healthy mice and rats (2,3,(6)(7)(8)(30)(31)(32). However, in the glioma model, CSF drainage along the exiting cranial nerves and downstream lymph nodes was shown to be reduced (7).…”

“…Traditional theories of CSF drainage suggest that CSF is generated by the ventricles and flows into the subarachnoid space, absorbed by the arachnoid particles and arachnoid villi, and carried to the venous sinuses (1)(2)(3)(4)(5). However, recent studies have revealed other CSF exit pathways (1): along the nerves, such as the olfactory and spinal nerves, leaving the skull to reach the cervical and spinal lymph nodes (2,3,6,7); flowing out through the "glymphatic system" (8)(9)(10)(11)(12)(13). In 2012, Iliff et al (8) discovered the "glymphatic system" in the mouse brain for the first time.…”