Distribution and stability of antisense phosphorothioate oligonucleotides in rodent brain following direct intraparenchymal controlled-rate infusion

Journal of Neurosurgery
W C BroaddusH F Young

Abstract

High-flow microinfusion is a novel technique for delivery of compounds directly into brain parenchyma, bypassing the blood-brain barrier. The feasibility of this technique has been demonstrated with low-molecular-weight compounds, macromolecular dyes, and proteins. Delivery of antisense oligonucleotides into brain parenchyma represents an additional potential application of this technique not previously described. In this report the authors sought to examine the distribution and disposition of phosphorothioate oligodeoxynucleotide (PS-ODN) for this reason. An 18-mer 35S-PS-ODN (Mr approximately 6000) was infused over 1 hour into the caudate putamen of Fischer 344 rats. At 1, 6, 12, 24, and 48 hours after beginning the infusion, the brains were extracted and analyzed using quantitative autoradiographic techniques. Cerebrospinal fluid (CSF) was also aspirated from the cisterna magna and was analyzed to determine the radioactivity and stability of the 35S-PS-ODN. At 1 hour, the infused ODN was uniformly distributed in brain tissue, with a maximum average concentration of 4806.5 +/- 210.5 nCi/g. This represents a tissue concentration of 19.2 +/- 0.84 microM. Extensive spread into surrounding parenchyma was observed over the ensuing...Continue Reading

References

Apr 1, 1992·Biopharmaceutics & Drug Disposition·G GoodarziK Watabe
Sep 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·S AgrawalJ Y Tang
Mar 1, 1990·Journal of Biochemical and Biophysical Methods·J M CampbellE Wickstrom
Oct 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·S AgrawalP C Zamecnik
Aug 1, 1988·Journal of Biochemical and Biophysical Methods·T A BaconE Wickstrom
Jan 1, 1970·Brain : a Journal of Neurology·L Bakay
Jan 1, 1970·Brain : a Journal of Neurology·L Bakay
Feb 1, 1982·Journal of Neurosurgery·A MarmarouK Shulman
Oct 1, 1994·Cellular and Molecular Neurobiology·B J ChiassonH A Robertson
Apr 11, 1995·Nucleic Acids Research·J Y MalteseR Narayanan
Feb 1, 1995·Current Opinion in Biotechnology·S Agrawal, R P Iyer
Aug 1, 1994·The American Journal of Physiology·S Napathorn, K R Spring
Mar 15, 1994·Proceedings of the National Academy of Sciences of the United States of America·R H BoboE H Oldfield
Jan 1, 1993·Methods in Molecular Biology·B C Froehler
May 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·L WhitesellL M Neckers

❮ Previous
Next ❯

Citations

Jun 25, 1999·The British Journal of Ophthalmology·W Y ShenP E Rakoczy
Jan 31, 2006·Neuro-oncology·Alexandre CarpentierAntoine F Carpentier
Sep 25, 2007·Journal of Neurosurgery·Nicholas J SzerlipRussell R Lonser
Aug 18, 2004·Journal of Neurosurgery·Zhi-Jian ChenPanos P Fatouros
Jul 1, 2006·Neurological Research·Kim A LopezJeffrey N Bruce
Jan 23, 2014·Journal of Medical Engineering & Technology·P J HaarW C Broaddus
May 25, 2006·Surgical Neurology·Shenghua ChuJie Zhang
Apr 27, 2001·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·N CholetG Bonvento
Aug 27, 1999·Antisense & Nucleic Acid Drug Development·S SeidmanH Soreq
Oct 12, 1999·The American Journal of Physiology·P F MorrisonE H Oldfield
Mar 17, 2000·Neurosurgery·J N BruceA T Parsa

❮ Previous
Next ❯

Methods Mentioned

BETA
antisense oligodeoxynucleotides
antisense oligonucleotides
electrophoresis
antisense oligonucleotide

Software Mentioned

M4

Related Concepts

Related Feeds

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

Blood Brain Barrier Regulation in Health & Disease

The blood brain barrier is essential in regulating the movement of molecules and substances in and out of the brain. Disruption to the blood brain barrier and changes in permeability allow pathogens and inflammatory molecules to cross the barrier and may play a part in the pathogenesis of neurodegenerative disorders. Here is the latest research in this field.

CSF & Lymphatic System

This feed focuses on Cerebral Spinal Fluid (CSF) and the lymphatic system. Discover the latest papers using imaging techniques to track CSF outflow into the lymphatic system in animal models.