a(CHEBI:macromolecule)
Here we show that meningeal lymphatic vessels have an essential role in maintaining brain homeostasis by draining macromolecules from the CNS (both CSF and ISF) into the cervical lymph nodes PubMed:30046111
Together, three different models of impaired meningeal lymphatic function (pharmacological, surgical and genetic) showed a significant impact on brain perfusion by CSF macromolecules PubMed:30046111
These findings, as has been suggested previously, demonstrate that the efflux of parenchymal and/or ISF macromolecules and the drainage of these macromolecules into dCLNs are impaired as a consequence of meningeal lymphatic ablation, thus functionally connecting meningeal lymphatics with CSF influx and ISF efflux mechanisms PubMed:30046111
These findings, as has been suggested previously, demonstrate that the efflux of parenchymal and/or ISF macromolecules and the drainage of these macromolecules into dCLNs are impaired as a consequence of meningeal lymphatic ablation, thus functionally connecting meningeal lymphatics with CSF influx and ISF efflux mechanisms PubMed:30046111
Notably, the rate of tracer influx into the brain parenchyma was significantly increased as a result of enhanced meningeal lymphatic function (Fig. 2k, l and Extended Data Fig. 6q, r) PubMed:30046111
Indeed, and in agreement with a previous study, old mice demonstrate reduced brain perfusion by CSF macromolecules compared to young counterparts (Extended Data Fig. 6a, b) PubMed:30046111
Impaired brain perfusion by CSF in old mice was accompanied by a decrease in meningeal lymphatic vessel diameter and coverage, as well as decreased drainage of CSF macromolecules into dCLNs in both females and males (Extended Data Fig. 6c–f) PubMed:30046111
Accordingly, the drainage of CSF macromolecules into dCLNs was significantly higher in sham-operated mice treated with mVEGF-C compared to all other groups (Fig. 2s, t) PubMed:30046111
Independently of the model, the level of CSF tracer drained into the dCLNs was comparable between transgenic mice with Alzheimer’s disease and age-matched wild-type littermates (Extended Data Fig. 8p–s) PubMed:30046111
Within the brain parenchyma, it was shown that aquaporin 4 (AQP4) expression by astrocytes plays an important role in the modulation of paravascular CSF macromolecule influx and efflux (through the glymphatic route) PubMed:30046111
Within the brain parenchyma, it was shown that aquaporin 4 (AQP4) expression by astrocytes plays an important role in the modulation of paravascular CSF macromolecule influx and efflux (through the glymphatic route) PubMed:30046111
Treatment with VEGF-C156S resulted in a significant increase in meningeal lymphatic diameter (Extended Data Fig. 7i, j), drainage of tracer from the CSF (Extended Data Fig. 7k, l), and paravascular influx of tracer into the brains of old mice (Extended Data Fig. 7m, n) PubMed:30046111
Together, three different models of impaired meningeal lymphatic function (pharmacological, surgical and genetic) showed a significant impact on brain perfusion by CSF macromolecules PubMed:30046111
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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.