title: A modified surgical procedure for microdialysis probe implantation in the lateral ventricle of a FVB mouse.
abstract: A modified surgical procedure is described to implant a microdialysis probe to sample ventricular cerebrospinal fluid (vCSF) in FVB mice. Microdialysis sampling of drugs in vCSF provides insight into drug penetration into the brain across the blood brain barrier (BBB) and the blood CSF barrier (BCB); however, this method has been reported primarily in larger animal species. Implanting a microdialysis probe in the lateral ventricle of a mouse is technically very challenging. The modification consisted of changes in the stereotaxic coordinates and insertion of the cannula and ultimately the probe at a 20 degrees 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 this modified procedure, the ventricular CSF to plasma AUC ratio of unbound topotecan lactone was greater than that previously reported using conventional methods. We speculate this is due to changes incorporated by the modified procedure that places the probe directly into the lateral ventricle allowing sampling of that discrete compartment. Thus, we propose that this modified procedure for placement of the microdialysis probe is superior to the conventional perpendicular method previously reported.
authors.affiliation: Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, Tennessee 38105-2794, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Shen
authors.forename: Charles
authors.initials: C
authors.lastname: Fraga
authors.forename: Christopher
authors.initials: C
authors.lastname: Calabrese
authors.forename: M Beth
authors.initials: MB
authors.lastname: McCarville
authors.forename: Paula
authors.initials: P
authors.lastname: Schaiquevich
authors.forename: Clinton F
authors.initials: CF
authors.lastname: Stewart
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics; D019540:Area Under Curve; D002552:Cerebral Ventricles / Q000601:surgery*; D005260:Female; D051379:Mice; D017551:Microdialysis; D019772:Topotecan / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; D019772:Topotecan