A modified surgical procedure for microdialysis probe implantation in the lateral ventricle of a FVB mouse
Jun Shen1, Charles Fraga, Christopher Calabrese
1Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, Tennessee 38105-2794, USA.
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.
Insights
This study presents a novel angled surgical technique for implanting microdialysis probes in mouse brains to measure drug levels in cerebrospinal fluid (CSF). This improved method enhances understanding of drug delivery across the blood-brain barrier.
Area of Science:
- Neuroscience
- Pharmacology
- Surgical Techniques
Background:
- Microdialysis of cerebrospinal fluid (CSF) is crucial for studying drug penetration across the blood-brain barrier (BBB) and blood-CSF barrier (BCB).
- Previous methods for microdialysis probe implantation in mouse lateral ventricles were technically challenging and primarily reported in larger animals.
Purpose of the Study:
- To describe a modified surgical procedure for accurate microdialysis probe implantation in the lateral ventricle of FVB mice.
- To evaluate the efficacy of this modified technique in assessing drug penetration into the brain's CSF.
Main Methods:
- A modified surgical approach involving angled insertion (20 degrees) of the microdialysis cannula and probe into the lateral ventricle of FVB mice.
- Confirmation of probe placement using ultrasound (US), micro-computed tomography (CT), and histologic analysis.
- Assessment of topotecan CSF penetration using the modified microdialysis technique.
Main Results:
- The modified angled insertion technique allowed for precise microdialysis probe placement in the mouse lateral ventricle.
- Studies using this method showed a higher ventricular CSF to plasma AUC ratio for unbound topotecan lactone compared to conventional methods.
- This suggests improved sampling of the specific CSF compartment.
Conclusions:
- The modified angled microdialysis probe implantation technique is superior to conventional perpendicular methods for sampling mouse ventricular CSF.
- This improved technique facilitates more accurate assessment of drug penetration into the central nervous system.
- The method offers valuable insights into drug distribution dynamics across the blood-brain and blood-CSF barriers in mice.
