Direct Intraventricular Delivery of Drugs to the Rodent Central Nervous System
Open Access
- 12 May 2013
- journal article
- video audio-media
- Published by MyJove Corporation in Journal of Visualized Experiments
- No. 75,p. e50326
- https://doi.org/10.3791/50326
Abstract
Due to an inability to cross the blood brain barrier, certain drugs need to be directly delivered into the central nervous system (CNS). Our lab focuses specifically on antisense oligonucleotides (ASOs), though the techniques shown in the video here can also be used to deliver a plethora of other drugs to the CNS. Antisense oligonucleotides (ASOs) have the capability to knockdown sequence-specific targets 1 as well as shift isoform ratios of specific genes 2. To achieve widespread gene knockdown or splicing in the CNS of mice, the ASOs can be delivered into the brain using two separate routes of administration, both of which we demonstrate in the video. The first uses Alzet osmotic pumps, connected to a catheter that is surgically implanted into the lateral ventricle. This allows the ASOs to be continuously infused into the CNS for a designated period of time. The second involves a single bolus injection of a high concentration of ASO into the right lateral ventricle. Both methods use the mouse cerebral ventricular system to deliver the ASO to the entire brain and spinal cord, though depending on the needs of the study, one method may be preferred over the other.Keywords
This publication has 16 references indexed in Scilit:
- Pathological Roles of Wild-Type Cu, Zn-Superoxide Dismutase in Amyotrophic Lateral SclerosisNeurology Research International, 2012
- Sustained Therapeutic Reversal of Huntington's Disease by Transient Repression of Huntingtin SynthesisNeuron, 2012
- Astrocytes from familial and sporadic ALS patients are toxic to motor neuronsNature Biotechnology, 2011
- Antisense Oligonucleotides Delivered to the Mouse CNS Ameliorate Symptoms of Severe Spinal Muscular AtrophyScience Translational Medicine, 2011
- Principles of Rodent Surgery for the New SurgeonJournal of Visualized Experiments, 2011
- Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse modelGenes & Development, 2010
- Antisense oligonucleotide therapy for neurodegenerative diseaseJCI Insight, 2006
- Protein aggregation and neurodegenerative diseaseNature Medicine, 2004
- Progress in Antisense Oligonucleotide TherapeuticsAnnual Review of Pharmacology and Toxicology, 1996
- Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosisNature, 1993