title: Direct, long-term intrathecal application of therapeutics to the rodent CNS.
abstract: Systemic application of therapeutics to the CNS tissue often results in subtherapeutic drug levels, because of restricted and selective penetration through the blood-brain barrier (BBB). Here, we give a detailed description of a standardized technique for intrathecal drug delivery in rodents, analogous to the technique used in humans. The intrathecal drug delivery method bypasses the BBB and thereby offers key advantages over oral or intravenous administration, such as maximized local drug doses with minimal systemic side effects. We describe how to deliver antibodies or drugs over several days or weeks from a s.c. minipump and a fine catheter inserted into the subdural space over the spinal cord (20 min operative time) or into the cisterna magna (10 min operative time). Drug levels can be sampled by quick and minimally invasive cerebrospinal fluid (CSF) collection from the cisterna magna (5 min procedure time). These techniques enable targeted application of any compound to the CNS for therapeutic studies in a wide range of CNS disease rodent models. Basic surgery skills are helpful for carrying out the procedures described in this protocol.
authors.affiliation: Brain Research Institute, University of Zurich, Zurich, Switzerland.|Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.
authors.forename: Benjamin V
authors.initials: BV
authors.lastname: Ineichen
authors.affiliation: Brain Research Institute, University of Zurich, Zurich, Switzerland.|Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.
authors.forename: Lisa
authors.initials: L
authors.lastname: Schnell
authors.affiliation: Brain Research Institute, University of Zurich, Zurich, Switzerland.|Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.
authors.forename: Miriam
authors.initials: M
authors.lastname: Gullo
authors.affiliation: Brain Research Institute, University of Zurich, Zurich, Switzerland.|Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.
authors.forename: Julia
authors.initials: J
authors.lastname: Kaiser
authors.affiliation: Brain Research Institute, University of Zurich, Zurich, Switzerland.|Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.
authors.forename: Marc P
authors.initials: MP
authors.lastname: Schneider
authors.affiliation: Brain Research Institute, University of Zurich, Zurich, Switzerland.|Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.
authors.forename: Alice C
authors.initials: AC
authors.lastname: Mosberger
authors.affiliation: Brain Research Institute, University of Zurich, Zurich, Switzerland.|Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Good
authors.affiliation: Clinic of Neurology, Helios Klinik Hagen-Ambrock, Hagen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Linnebank
authors.affiliation: Brain Research Institute, University of Zurich, Zurich, Switzerland.|Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Schwab
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D057785:Catheters; D002946:Cisterna Magna / Q000378:metabolism; D005260:Female; D007278:Injections, Spinal / Q000295:instrumentation / Q000379:methods*; D008297:Male; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000378:metabolism; D051381:Rats; D013355:Subdural Space / Q000378:metabolism; D013997:Time Factors
chemical_list: D004364:Pharmaceutical Preparations