Cerebral arterial pulsation drives paravascular CSF-Interstitial fluid exchange in the murine brain

Jeffrey J. Iliff, Minghuan Wang, Douglas M. Zeppenfeld, Arun Venkataraman, Benjamin A. Plog, Yonghong Liao, Rashid Deane, Maiken Nedergaard

Research output: Contribution to journalArticlepeer-review

420 Scopus citations

Abstract

CSF from the subarachnoid space moves rapidly into the brain along paravascular routes surrounding penetrating cerebral arteries, exchanging with brain interstitial fluid (ISF) and facilitating the clearance of interstitial solutes, such as amyloidβ, in a pathway that we have termed the "glymphatic" system. Prior reports have suggested that paravascular bulk flow of CSF or ISF may be driven by arterial pulsation. However, cerebral arterial pulsation could not be directly assessed. In the present study, we use in vivo two-photon microscopy in mice to visualize vascular wall pulsatility in penetrating intracortical arteries. We observed that unilateral ligation of the internal carotid artery significantly reduced arterial pulsatility by ~50%, while systemic administration of the adrenergic agonist dobutamine increased pulsatility of penetrating arteries by ~60%. When paravascular CSF-ISF exchange was evaluated in real time using in vivo two-photon and ex vivo fluorescence imaging, we observed that internal carotid artery ligation slowed the rate of paravascular CSF-ISF exchange, while dobutamine increased the rate of paravascular CSF-ISF exchange. These findings demonstrate that cerebral arterial pulsatility is a key driver of paravascular CSF influx into and through the brain parenchyma, and suggest that changes in arterial pulsatility may contribute to accumulation and deposition of toxic solutes, including amyloidβ, in the aging brain.

Original languageEnglish (US)
Pages (from-to)18190-18199
Number of pages10
JournalJournal of Neuroscience
Volume33
Issue number46
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Cerebral arterial pulsation drives paravascular CSF-Interstitial fluid exchange in the murine brain'. Together they form a unique fingerprint.

Cite this