Acute Cellular and Functional Changes With a Combinatorial Treatment of Ion Channel Inhibitors Following Spinal Cord Injury

Frontiers in Molecular Neuroscience
Ryan L O'Hare DoigStuart I Hodgetts

Abstract

Reducing the extent of secondary degeneration following spinal cord injury (SCI) is necessary to preserve function, but treatment options have thus far been limited. A combination of the ion channel inhibitors Lomerizine (Lom), YM872 and oxATP, to inhibit voltage-gated Ca2+ channels, Ca2+ permeable AMPA receptors, and purinergic P2X7 receptors respectively, effectively limits secondary consequences of injury in in vitro and in vivo models of CNS injury. Here, we investigated the efficacy of these inhibitors in a clinically relevant model of SCI. Fischer (F344) rats were subjected to a moderate (150 kD) contusive SCI at thoracic level T10 and assessed at 2 weeks or 10 weeks post-injury. Lom was delivered orally twice daily and YM872 and oxATP were delivered via osmotic mini-pump implanted at the time of SCI until 2 weeks following injury. Open field locomotion analysis revealed that treatment with the three inhibitors in combination improved the rate of functional recovery of the hind limb (compared to controls) as early as 1-day post-injury, with beneficial effects persisting to 14 days post-injury, while all three inhibitors were present. At 2 weeks following combinatorial treatment, the functional improvement was associated w...Continue Reading

References

May 1, 1986·Journal of Neurosurgery·H A Kontos, E P Wei
Feb 1, 1995·Journal of Neurotrauma·D M BassoJ C Bresnahan
Feb 24, 1994·The New England Journal of Medicine·J F Ditunno, C S Formal
Jan 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·H H RefsgaardE R Stadtman
Nov 4, 2000·Journal of Neurotrauma·A LewénP H Chan
Nov 4, 2000·Journal of Neurotrauma·M S BeattieJ C Bresnahan
Nov 25, 2000·Journal of the Neurological Sciences·L Van Den BoschW Robberecht
Jan 10, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·H KamencicB H Juurlink
Mar 16, 2001·Trends in Neurosciences·C MatuteM V Sánchez-Gómez
Aug 22, 2001·Microscopy Research and Technique·L L Jones, M H Tuszynski
Sep 25, 2002·Physiological Reviews·R Alan North
Jun 25, 2003·Experimental Neurology·S ChenN G Harris
Oct 28, 2003·Investigative Ophthalmology & Visual Science·Yasuhiro TamakiKen Tomita
Mar 23, 2004·Current Molecular Medicine·Peter K Stys
Apr 30, 2004·Journal of Neurotrauma·Michael D NorenbergAlex Marcillo
Apr 23, 2005·The Journal of Comparative Neurology·Minodora O Totoiu, Hans S Keirstead

❮ Previous
Next ❯

Methods Mentioned

BETA
electron microscopy

Software Mentioned

ALZET
GraphPad Prism
Fiji
GraphPad
ARRIVE

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.