Bulk flow of cerebrospinal fluid observed in periarterial spaces is not an artifact of injection

Aditya Raghunandan, Antonio Ladron-De-guevara, Jeffrey Tithof, Humberto Mestre, Ting Du, Maiken Nedergaard, John H. Thomas, Douglas H. Kelley

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


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 (CM) 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 CM 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.

Original languageEnglish (US)
Article numbere65958
StatePublished - Mar 2021

Bibliographical note

Funding Information:
National Institutes of Health- RF1AG057575- Maiken Nedergaard, John H Thomas, Douglas H Kelley, Aditya Raghunandan; Army Research Office- MURI W911NF1910280- Antonio Ladron-de-Guevara, Humberto Mestre, Maiken Nedergaard, John H Thomas, Douglas H Kelley, Ting Du; Burroughs Wellcome Fund- Career Award at the Scientific Interface- Jeffrey Tithof.

Publisher Copyright:
© Raghunandan et al.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.


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