This article discusses the technique of intracerebroventricular injection for drug delivery in the treatment of leptomeningeal disease. It highlights the surgical procedure involved in implanting a Murine Ommaya reservoir for direct access to cerebrospinal fluid (CSF).
In leptomeningeal disease, cancer cells from other body organs metastasize to cerebrospinal fluid or CSF contained within leptomeninges - thin tissue layers surrounding the brain.
The intracerebroventricular injection facilitates direct drug administration in CSF, evading the blood-brain barrier.
To begin, prep an anesthetized mouse in the prone position.
Incise the head to reveal the skull. Locate the bregma - the junction point of coronal and sagittal sutures.
Using a microdrill, drill a hole in the skull at an appropriate distance from the bregma to access the outermost meningeal layer of dense connective tissue - the dura mater.
Then, gently insert the ommaya - a small injection port - into the hole.
Once done, suture the surrounding skin and allow the ommaya to affix for an optimum duration.
Next, connect the syringe filled with the desired drug suspension to the ommaya.
After setting a suitable flow rate, inject the drug suspension into the dura mater.
The ommaya provides a sterile pathway for direct drug delivery into the CSF in the cerebral ventricles of the brain.
Now, detach the syringe and leave the ommaya intact in the skull for subsequent dosage.
Allow the mouse to recover.
Over time, the drug molecules migrate towards the cancer site and prevent the growth and proliferation of cancer cells.
Assemble the Murine Ommaya injection device using a 25G miniature injection port and a 1-millimeter spacer disc.
Use a cyanoacrylate sterile adhesive to ensure the penetration of approximately 2.5 millimeters of the metal cannula into the right cerebral hemisphere and prepare the skin according to sterile technique.
Make a small skin incision, followed by blunt dissection of the underlying subcutaneous tissues to expose the skull. Dry the skull using hydrogen peroxide-soaked cotton-tipped applicator sticks.
Drill a 0.9-millimeter burr hole in the skull, 0.5 millimeters posterior and 1.1 millimeters lateral of the bregma, to expose the dura mater.
Move the microdrill aside and gently score the bone immediately surrounding the burr hole. Affix an injection port to the skull using a cyanoacrylate sterile adhesive and insert it to a depth of approximately 2.5 millimeters.
Suture the incision using 4-0 non-absorbable nylon sutures in an interrupted stitch pattern or purse string suture. House post-surgery mice in individual cages for recovery.
To dose the mouse, access the Murine Ommaya using a port injection adapter and a Hamilton syringe. Using forceps, hold the top of the miniature injection port and gently insert the port injector adapter fully into the port's septum.
Once the injection is made, detach the Murine Ommaya from the port injection adapter with forceps.
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