Abstract
Context/Objectives: Spinal cord injury (SCI) results in significant neuronal and glial cell death resulting in impaired neurological and motor function. Uncontrolled Ca2+ entry results in excitotoxicity and cell death. In this study, we examine the use of a BK channel activator, Isopimaric acid (ISO), as a neuroprotective agent post-SCI as this channel is involved in regulating Ca2+ entry.Design:By using a 25-g clip compression at the T6 level, we generated a SCI event in wistar rats. At 1 h post-injury we administered ISO (BK channel activator), the BK channel inhibitor iberiotoxin (IbTx), or a vehicle control for 4 weeks via mini osmotic pump (pump capacity). For 8 weeks post-injury, gait analysis of motor function was performed. At the end of 8 weeks, the extent of myelination in the spinal cord was assessed in addition to the electrophysiological profile.Results:Our immunohistological data suggests that ISO treatment leads to an increase or preservation of myelinated axonal tracts. This was further supported by our electrophysiological studies which demonstrate higher compound action potential amplitudes and speed of transmission in ISO-treated animals compared to inj-non-treated. Finally, treatment with ISO significantly improved motor function in our test model.Conclusion: In conclusion, activation of the BK channel during acute SCI may be a novel therapeutic target for acute SCI.
Highlights
In north America there are over 1.3 million individuals with spinal cord injury (SCI) and an annual incidence rate of 30–70 cases per million people [1, 2]
In order to investigate the extent of myelinated neurons postSCI, rats underwent a 25 g aneurysm clip injury to the thoracic spinal cord (T5-T7)
Spinal cords were sagittally sectioned and stained with Myelin Basic Protein (MBP- green), and to determine extent of axonal tracts, sections were stained with Neurofilament (NF- red) antibodies
Summary
In north America there are over 1.3 million individuals with spinal cord injury (SCI) and an annual incidence rate of 30–70 cases per million people [1, 2]. Mitigation of injury severity as well as return of normal function are primary concerns, current therapies are unable to do either. During SCI, there are typically two injury events. Primary damage is caused by the mechanical impact to the spinal cord from deformities of surrounding anatomical structures. The cellular membranes are disrupted, the myelin sheath starts to break down, and localized hemorrhaging of the spinal cord occurs.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
