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Vasomotor influences on glymphatic-lymphatic coupling and solute trafficking in the central nervous system

Authors :
Jeffrey J. Iliff
James R. Goodman
Source :
J Cereb Blood Flow Metab
Publication Year :
2019
Publisher :
SAGE Publications, 2019.

Abstract

Despite the recent description of meningeal lymphatic vessels draining solutes from the brain interstitium and cerebrospinal fluid (CSF), the physiological factors governing cranial lymphatic efflux remain largely unexplored. In agreement with recent findings, cervical lymphatic drainage of 70 kD and 2000 kD fluorescent tracers injected into the adult mouse cortex was significantly impaired in the anesthetized compared to waking animals (tracer distribution across 2.1 ± 4.5% and 23.7 ± 15.8% of deep cervical lymph nodes, respectively); however, free-breathing anesthetized mice were markedly hypercapnic and acidemic (paCO2 = 64 ± 8 mmHg; pH = 7.22 ± 0.05). Mechanical ventilation normalized arterial blood gases in anesthetized animals, and rescued lymphatic efflux of interstitial solutes in anesthetized mice. Experimental hypercapnia blocked cervical lymphatic efflux of intraparenchymal tracers. When tracers were injected into the subarachnoid CSF compartment, glymphatic influx into brain tissue was virtually abolished by hypercapnia, while lymphatic drainage was not appreciably altered. These findings demonstrate that cervical lymphatic drainage of interstitial solutes is, in part, regulated by upstream changes in glymphatic CSF-interstitial fluid exchange. Further, they suggest that maintaining physiological blood gas values in studies of glymphatic exchange and meningeal lymphatic drainage may be critical to defining the physiological regulation of these processes.

Details

ISSN :
15597016 and 0271678X
Volume :
40
Database :
OpenAIRE
Journal :
Journal of Cerebral Blood Flow & Metabolism
Accession number :
edsair.doi.dedup.....4292bd9dfc473c0dad3faf9962949b69
Full Text :
https://doi.org/10.1177/0271678x19874134