Development of a simple, rapid, and robust intrathecal catheterization method in the rat by Curt Mazur & Bethany Fitzsimmons & Fredrik Kamme & Brandon Nichols & Berit Powers & Ed Wancewicz instant download

Development of a simple, rapid, and robust intrathecal catheterization method in the rat by Curt Mazur & Bethany Fitzsimmons & Fredrik Kamme & Brandon Nichols & Berit Powers & Ed Wancewicz instant download

a b s t r a c tArticle history:Background: The blood brain barrier (BBB) is an impediment to the development of large and highlyReceived 9 November 2016charged molecules as therapeutics for diseases and injuries ofthe central nervous system (CNS).AntisenseReceived in revised form 30 January 2017oligonucleotides (ASOs) are large (6000–8000 MW) andhighly charged and therefore donot cross theBBB.Accepted 1 February 2017A method of circumventing the blood brain barrier to test ASOs, and other non-BBB penetrant molecules,Available online 2 February 2017as CNS therapeutics is the direct administration of these molecules to the CNS tissue or cerebral spinalKeywords:fluid.New method: We developed a rapid, simple and robust method for the intrathecal catheterization of ratsIntrathecalto test putatively therapeutic antisense oligonucleotides. This method utilizes 23-gauge needles, simplyDrug deliveryconstructed ½ in. long 19-gauge guide cannulas and 8 cm long plastic PE-10 sized catheters.CatheterComparison with existing methods: Unlike the cisterna magna approach, this method uses a lumbarAntisense oligonucleotideapproach for intrathecal catheterization with the catheter residing entirely in the cauda equina spaceRatCerebral spinal fluidminimizing spinal cord compression. Readily available materials and only a few specialized pieces ofThecal sackequipment, which are easily manufactured, are used for this intrathecal catheterization method.Subarachnoid spaceConclusions: This method is easy to learn and has been taughtto multiple in house surgeons, collaboratorsand contractlaboratories. Greater than90%catheterizationsuccess is routinely achieved withthismethodand as many as 100 catheters can be placed and test substance administered in one 6-h period. Thismethod has allowed the pre-clinical testing of hundreds of ASOs as therapeutics for CNS indications.© 2017 Elsevier B.V. All rights reserved.