Cerebral Open Flow Microperfusion to Monitor Drug Transport Across the Blood-Brain Barrier

Abstract

Drugs for neurological diseases have to cross the blood-brain barrier (BBB) to induce their therapeutic effect. In vivo drug quantification in the brain is challenging, because invasive methods damage the BBB and measurement results may be confounded by drug leakage from the blood into the brain through the disrupted BBB. Cerebral open flow microperfusion (cOFM) is an in vivo sampling technique that allows BBB healing and re-establishment after probe implantation and before sampling is performed. It therefore provides the opportunity to sample compounds in cerebral interstitial fluid with an intact BBB. This article comprehensively describes the experimental setup and procedures, perfusate requirements, critical parameters, common problems that may occur, and their causes and solutions. Typical results from a cOFM sampling experiment are presented and discussed. This protocol provides a tool for performing pharmacokinetic and pharmacodynamic studies in mouse or rat brain with an intact BBB. © 2019 by John Wiley & Sons, Inc.