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Cited by 220Cerebrospinal fluid and hydrocephalusNeural dynamics and brain functionIon Transport and Channel Regulation

The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.

Neuronal dynamics direct cerebrospinal fluid perfusion and brain clearance

Open access
Jiang-Xie, Li-Feng, Drieu, Antoine, Bhasiin, Kesshni, Quintero, Daniel, Smirnov, Igor, Kipnis, Jonathan·2024·Nature
DOI 10.1038/s41586-024-07108-6PMC PMC12054998
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Abstract

The accumulation of metabolic waste is a leading cause of numerous neurological disorders, yet we still have only limited knowledge of how the brain performs self-cleansing. Here we demonstrate that neural networks synchronize individual action potentials to create large-amplitude, rhythmic and self-perpetuating ionic waves in the interstitial fluid of the brain. These waves are a plausible mechanism to explain the correlated potentiation of the glymphatic flow 1,2 through the brain parenchyma. Chemogenetic flattening of these high-energy ionic waves largely impeded cerebrospinal fluid infiltration into and clearance of molecules from the brain parenchyma. Notably, synthesized waves generated through transcranial optogenetic stimulation substantially potentiated cerebrospinal fluid-to-interstitial fluid perfusion. Our study demonstrates that neurons serve as master organizers for brain clearance. This fundamental principle introduces a new theoretical framework for the functioning of macroscopic brain waves.

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  • Glymphatic flow is enhanced by optogenetic stimulation of excitatory neurons in hippocampus across a broad range of frequencies.

    “glymphatic flow is enhanced by optogenetic stimulation of excitatory neurons in hippocampus across a broad range of frequencies89”

    From Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep (2025) · cites this paper as [89]

    The “Synthesized waves enhance CSF-to-ISF perfusion” section reports increased tracer infiltration in the hippocampus after optogenetic stimulation at 1 Hz and 8 Hz. The Methods identify a CaMKIIa-ChRmine vector used for activation. The claim overstates the frequency evidence: the paper tests two stimulation frequencies, not a broad range. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Neural synchrony drives glymphatic clearance.

    “Common to both studies was the finding that neural synchrony drive glymphatic clearance.”

    From Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep (2025) · cites this paper as [89]

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Metadata

Authors
Jiang-Xie, L.-F., Drieu, A., Bhasiin, K., Quintero, D., Smirnov, I., & Kipnis, J.
Affiliations
Washington University in St. Louis (US)
Corresponding author
  • Jiang-Xie, Li-Feng
  • Kipnis, Jonathan
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2024-02-28
Volume
627
Issue
8002
Pages
157-164
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/s41586-024-07108-6
PMC
PMC12054998
OpenAlex
W4392242192
Cited by
220
References
16
Citations by year
2026: 89 · 2025: 98 · 2024: 33
FWCI
55.12
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • National Institutes of Health
  • National Center for Complementary and Integrative Health (DP1AT010416, R01AT011419)
Topics
  • Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
Keywords
glymphatic system, cerebrospinal fluid flow, brain clearance, neuronal synchronization, interstitial fluid, brain parenchyma, optogenetic stimulation, chemogenetic inhibition, brain waste clearance, neural oscillations
MeSH terms
Parenchymal Tissue, Glymphatic System, Action Potentials, Brain, Cerebrospinal Fluid, Ions, Kinetics, Nerve Net, Neurons, Extracellular Fluid, Brain Waves, Optogenetics

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