Bulk flow of cerebrospinal fluid observed in periarterial spaces is not an artifact of injection
- University of Rochester, United States
- University of Rochester Medical Center, United States
- University of Minnesota, United States
Abstract
Cerebrospinal fluid (CSF) flowing through periarterial spaces is integral to the brain's mechanism for clearing metabolic waste products. Experiments that track tracer particles injected into the cisterna magna of mouse brains have shown evidence of pulsatile CSF flow in perivascular spaces surrounding pial arteries, with a bulk flow in the same direction as blood flow. However, the driving mechanism remains elusive. Several studies have suggested that the bulk flow might be an artifact, driven by the injection itself. Here, we address this hypothesis with new in vivo experiments where tracer particles are injected into the cisterna magna using a dual-syringe system, with simultaneous injection and withdrawal of equal amounts of fluid. This method produces no net increase in CSF volume and no significant increase in intracranial pressure. Yet, particle-tracking reveals flows that are consistent in all respects with the flows observed in earlier experiments with single-syringe injection.
Data availability
All data generated or analyzed for this study are included in the manuscript. Source data files have been provided for Figures 4a, 4d, 4e, and 5i.The particle-tracking Matlab code used in this study is available in the public domain GitLab repository found here: https://gitlab-public.circ.rochester.edu/araghuna/bulk-flow-is-not-an-artifact_raghunandan_et_al_2021.git
Article and author information
Author details
Aditya Raghunandan
Funding
National Institutes of Health (RF1AG057575)
- Maiken Nedergaard
- John H Thomas
- Douglas H Kelley
Army Research Office (MURI W911NF1910280)
- Antonio Ladron-de-Guevara
- Humberto Mestre
- Maiken Nedergaard
- John H Thomas
- Douglas H Kelley
Burroughs Wellcome Fund (Career Award at the Scientific Interface)
- Jeffrey Tithof
The funding agencies did not influence study design, data collection, and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experiments were approved and conducted in accordance with the relevant guidelines and regulations stipulated by theUniversity Committee on Animal Resources of the University of Rochester Medical Center (Protocol No. 2011-023), certifiedby Association for Assessment and Accreditation of Laboratory Animal Care.
Copyright
© 2021, Raghunandan et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Bulk flow of cerebrospinal fluid observed in periarterial spaces is not an artifact of injection
eLife 10:e65958.
https://doi.org/10.7554/eLife.65958
