A modified surgical procedure for microdialysis probe implantation in the lateral ventricle of a FVB mouse

SHEN J; FRAGA C; CALABRESE C; MCCARVILLE MB; SCHAIQUEVICH P; STEWART CF

JOURNAL OF PHARMACEUTICAL SCIENCES

Wiley-Liss

Año: 2008 vol. 31 p. 1 - 10

0022-3549

ABSTRACT: A modified surgical procedure is described to implant a microdialysis probeto sample ventricular cerebrospinal fluid (vCSF) in FVB mice. Microdialysis sampling ofdrugs in vCSF provides insight into drug penetration into the brain across the blood brainbarrier (BBB) and the blood CSF barrier (BCB); however, this method has been reportedprimarily in larger animal species. Implanting a microdialysis probe in the lateralventricle of amouse is technically very challenging. Themodification consisted of changesin the stereotaxic coordinates and insertion of the cannula and ultimately the probe at a208 angle. Exact placement of the probe was confirmed using ultrasound (US), micro-computed tomography (CT), and histologic review of serial paraffin sections. Additionally,studies of topotecan CSF penetration in the FVB mouse were conducted. With thismodified procedure, the ventricular CSF to plasma AUC ratio of unbound topotecanlactone was greater than that previously reported using conventional methods. Wespeculate this is due to changes incorporated by the modified procedure that placesthe probe directly into the lateral ventricle allowing sampling of that discrete compart-ment. Thus, we propose that this modified procedure for placement of the microdialysisprobe is superior to the conventional perpendicular method previously reported.