MCI-186 prevents spinal cord damage and affects enzyme levels of nitric oxide synthase and Cu/Zn superoxide dismutase after transient ischemia in rabbits
ABSTRACT The mechanism of spinal cord injury is believed to be related to the vulnerability of spinal motor neuron cells against ischemia. We tested whether MCI-186, which is useful for treating ischemic damage in the brain, can protect against ischemic spinal cord damage.
After induction of ischemia, 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 Cu/Zn superoxide dismutase, neuronal nitric oxide synthase, and endothelial nitric oxide synthase.
MCI-186 eased the functional deficits and increased the number of motor neurons after ischemia. The induction of neuronal nitric oxide synthase was significantly reduced by the treatment with MCI-186. Furthermore, the increase in the induction of endothelial nitric oxide synthase and Cu/Zn superoxide dismutase was more pronounced.
These results indicate that MCI-186 may protect motor neurons from ischemic injury by reducing neuronal nitric oxide synthase and increasing endothelial nitric oxide synthase. MCI-186 may be a strong candidate for use as a therapeutic agent in the treatment of ischemic spinal cord injury.
Full-textDOI: · Available from: Masahiro Sakurai, Aug 13, 2015
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- "reducing brain damage when applied in this model of sAD (Kaur and Ling, 2008). Several reports have related the modulatory effects of edaravone on lipid peroxidation, PC formation and antioxidant enzymes as observed in hypoxia/ischemia and ischemic–reperfusion injury experiments (Takahashi et al., 2003; Zhang et al., 2005). In agreement with these findings, we report here that edaravone treatment markedly restored the biochemical changes as well as cognitive deficits induced by ICV- STZ infusion. "
ABSTRACT: Oxidative stress is implicated as an important factor in the development of Alzheimer's disease (AD). In the present study, we have investigated the effects of edaravone (9mg/kg, 3-Methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, in a streptozotocin (STZ-3mg/kg) induced rat model of sporadic AD (sAD). Treatment with edaravone significantly improved STZ-induced cognitive damage as evaluated in Morris water maze and step-down tests and markedly restored changes in malondialdehyde (MDA), 4-hydroxy-2-nonenal (4-HNE) adducts, hydroxyl radical (·OH), hydrogen peroxide (H2O2), total superoxide dismutase (T-SOD), reduced glutathione (GSH), glutathione peroxidase (GPx) and protein carbonyl (PC) levels. In addition, histomorphological observations confirmed the protective effect of edaravone on neuronal degeneration. Moreover, hyperphosphorylation of tau resulting from intracerebroventricular streptozotocin (ICV-STZ) injection was decreased by the administration of edaravone. These results provide experimental evidence demonstrating preventive effects of edaravone on cognitive dysfunction, oxidative stress and hyperphosphorylation of tau in ICV-STZ rats. Since edaravone has been used for treatment of patients with stroke, it represents a safe and established therapeutic intervention that has the potential for a novel application in the treatment of age-related neurodegenerative disorders associated with cognitive decline, such as AD.NeuroToxicology 08/2013; 38. DOI:10.1016/j.neuro.2013.07.007 · 3.05 Impact Factor
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