Direct Measurement of Cerebrospinal Fluid Production in Mice

Cell Rep. 2020 Dec 22;33(12):108524. doi: 10.1016/j.celrep.2020.108524.


The emerging interest in brain fluid transport has prompted a need for techniques that provide an understanding of what factors regulate cerebrospinal fluid (CSF) production. Here, we describe a methodology for direct quantification of CSF production in awake mice. We measure CSF production by placing a catheter in a lateral ventricle, while physically blocking outflow from the 4th ventricle. Using this methodology, we show that CSF production increases during isoflurane anesthesia, and to a lesser extent with ketamine/xylazine anesthesia, relative to the awake state. Aged mice have reduced CSF production, which is even lower in aged mice overexpressing amyloid-β. Unexpectedly, CSF production in young female mice is 30% higher than in age-matched males. Altogether, the present observations imply that a reduction in CSF production might contribute to the age-related risk of proteinopathies but that the rate of CSF production and glymphatic fluid transport are not directly linked.

Keywords: aging; amyloid-β; glymphatic system; sex difference; sleep-wake cycle.

Publication types

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

MeSH terms

  • Animals
  • Cerebrospinal Fluid / metabolism*
  • Female
  • Glymphatic System / metabolism*
  • Male
  • Mice