Research articleDevelopment of a simple, rapid, and robust intrathecal catheterization method in the rat

- A simple, rapid and robust method for the intrathecal catheterization of rats was developed.
- The method uses a lumbar spinal approach minimizing insertion of catheter material into the thecal space.
- Readily available materials and simply created custom guide cannulas are used in the method.
- This method has been taught to many individuals and has been used for the placement of thousands of intrathecal catheters in rats.
- Little to no adverse effects of the placement of the intrathecal catheters have been observed with this method.

BackgroundThe blood brain barrier (BBB) is an impediment to the development of large and highly charged molecules as therapeutics for diseases and injuries of the central nervous system (CNS). Antisense oligonucleotides (ASOs) are large (6000-8000 MW) and highly charged and therefore do not cross the BBB. A method of circumventing the blood brain barrier to test ASOs, and other non-BBB penetrant molecules, as CNS therapeutics is the direct administration of these molecules to the CNS tissue or cerebral spinal fluid.New methodWe developed a rapid, simple and robust method for the intrathecal catheterization of rats to test putatively therapeutic antisense oligonucleotides. This method utilizes 23-gauge needles, simply constructed ½ in. long 19-gauge guide cannulas and 8 cm long plastic PE-10 sized catheters.Comparison with existing methodsUnlike the cisterna magna approach, this method uses a lumbar approach for intrathecal catheterization with the catheter residing entirely in the cauda equina space minimizing spinal cord compression. Readily available materials and only a few specialized pieces of equipment, which are easily manufactured, are used for this intrathecal catheterization method.ConclusionsThis method is easy to learn and has been taught to multiple in house surgeons, collaborators and contract laboratories. Greater than 90% catheterization success is routinely achieved with this method and as many as 100 catheters can be placed and test substance administered in one 6-h period. This method has allowed the pre-clinical testing of hundreds of ASOs as therapeutics for CNS indications.