Neuronal dynamics direct cerebrospinal fluid perfusion and brain clearance

Li-Feng Jiang-Xie (), Antoine Drieu, Kesshni Bhasiin, Daniel Quintero, Igor Smirnov and Jonathan Kipnis ()
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Li-Feng Jiang-Xie: Washington University in St Louis
Antoine Drieu: Washington University in St Louis
Kesshni Bhasiin: Washington University in St Louis
Daniel Quintero: Washington University in St Louis
Igor Smirnov: Washington University in St Louis
Jonathan Kipnis: Washington University in St Louis

Nature, 2024, vol. 627, issue 8002, 157-164

Abstract: 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 flow1,2 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.

Date: 2024
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DOI: 10.1038/s41586-024-07108-6

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