Design and Testing of a Device for Drug Infusion
and Collection of Continuous or Batch Cerebrospinal Fluid (CSF) in
Rats: Pharmacokinetic Study of CSF Fluorescein Injected
Intravenously and Infused Minocycline
Carlos Valdes1,
Jose L Martinez2 and Claudio Laurido1*
1Laboratory
of Neurobiology, Faculty of Chemistry and Biology; 2Vicerrectory
of Research, Development and Innovation, University of Santiago of
Chile, P.O. Box 40, Correo 33, 917002, Santiago, Chile *Corresponding author: claudio.laurido@usach.cl
Abstract
Many devices for obtaining cerebrospinal fluid
(CSF) have been published. However, none of them allows the infusion and
collection of CSF in a continuous or discontinuous base. The purpose for the
design of this system is based on the possibility of injecting drugs of rapid or
slow absorption (encapsulated in nanoparticles). Also useful, for studying the
pharmacokinetics of drugs injected outside the cerebrospinal compartment (i.e.
intraperitoneal), which can be followed over time by collecting small samples of
CSF. Among the advantages of this system are the high yield of the CSF
withdrawal (102.5±17 µL), without the presence of blood
(around 99% of the rats tested (n=20)). Also, the survival of rats approaches
around 75 % after a weekly CSF withdrawal repeated for one month (n=6). Finally,
there was no need of a surgical procedure to expose the dura in the cisterna
magna to withdraw CSF. The use of a stereotaxic device for securing the rat head
allowed us to insert the collecting needle in a fixed place, without the
guessing of other methods. Even though the use of this system appears to be
expensive, it is worthwhile using it in pro of obtaining blood free CSF samples.
In order to test this device, we assayed CSF for blood contamination, CSF
protein determination and the pharmacokinetics of fluorescein in the CSF after
the intravenous injection of the dye. Also, we studied the kinetic of infused
minocycline into the CSF compartment. We can conclude that this device might
become an indispensable tool in studies that involve manipulating the
cerebrospinal compartment composition.
Key words:
Cerebrospinal fluid,
Collection of CSF,
Infusion of drugs, Rat