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Updated: Aug 23, 2026
Spinal Cord Neurons Isolation and Culture from Neonatal Mice
Published on: July 11, 2017
MCI-186 reduces oxidative cellular damage and increases DNA repair function in the rabbit spinal cord after transient
Goro Takahashi1, Masahiro Sakurai, Koji Abe
1Department of Cardiovascular Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aoba-ku, Sendai 980-8574, Japan.
Background:
Paraplegia is a serious complication of operations on the thoracic and thoracoabdominal aorta. To investigate the mechanism by which motor neurons are damaged during these operations, we have reported a rabbit model of spinal cord ischemia. We also tested whether a free radical scavenger MCI-186 that is useful for treating ischemic damage in the brain can protect against ischemic spinal cord damage.
Methods:
Fifteen minutes of ischemia was induced, then MCI-186 or vehicle was injected intravenously. Cell damage was analyzed by observing the function of the lower limbs and by counting the number of motor neurons. To investigate the mechanism by which MCI-186 prevents ischemic spinal cord damage, we observed the immunoreactivity of 8-hydroxy-2'-deoxyguanosine as an oxidative DNA damage marker and redox effector as a DNA repair marker.
Results:
In sham control, 8-hydroxy-2'-deoxyguanosine was not observed, and the nuclear expression of redox effector was observed. In vehicle injection group (group I), the nuclear expression of 8-hydroxy-2'-deoxyguanosine was observed at 1 and 2 days after reperfusion. The nuclear expression of redox effector was observed at 8 hours and 1 day, and disappeared at 2 days after transient ischemia. In MCI-186 injection group (group M), the nuclear expression of 8-hydroxy-2'-deoxyguanosine was not observed, and redox effector was observed at 8 hours and 1 and 2 days.
Conclusions:
These results suggest that redox effector decreased in motor neurons after transient ischemia and this reduction preceded oxidative DNA damage. MCI-186 works as a radical scavenger and reduced oxidative DNA damage, so redox effector did not disappear. MCI-186 could be a strong candidate for a use as a therapeutic agent in the treatment of ischemic spinal cord injury.
Insights
A study on rabbits found that the free radical scavenger MCI-186 protected motor neurons from ischemic damage. MCI-186 reduced oxidative DNA damage, suggesting its potential as a therapeutic agent for spinal cord injury.
Area of Science:
- Neuroscience
- Ischemic Injury Research
- Pharmacology
Background:
- Paraplegia is a significant risk following thoracic and thoracoabdominal aortic surgeries.
- Understanding motor neuron damage mechanisms during these operations is crucial.
- A rabbit model of spinal cord ischemia was established to study these mechanisms.
Purpose of the Study:
- To investigate the protective effects of the free radical scavenger MCI-186 against ischemic spinal cord damage.
- To elucidate the mechanism by which MCI-186 prevents motor neuron injury.
- To assess MCI-186's efficacy in a rabbit model of transient spinal cord ischemia.
Main Methods:
- Induction of 15 minutes of spinal cord ischemia in rabbits, followed by intravenous injection of MCI-186 or vehicle.
- Assessment of motor neuron function and cell counts to evaluate damage.
- Measurement of 8-hydroxy-2'-deoxyguanosine (oxidative DNA damage marker) and redox effector (DNA repair marker) immunoreactivity.
Main Results:
- Vehicle-treated group showed oxidative DNA damage and decreased redox effector expression post-ischemia.
- MCI-186 treatment prevented the observation of oxidative DNA damage.
- In the MCI-186 group, redox effector expression was maintained for up to 2 days post-ischemia.
Conclusions:
- Transient ischemia leads to a decrease in motor neuron redox effector, preceding oxidative DNA damage.
- MCI-186, acting as a radical scavenger, mitigates oxidative DNA damage and preserves redox effector levels.
- MCI-186 shows promise as a therapeutic agent for treating ischemic spinal cord injury.
