Neuroprotection by diarylpropionitrile in mice with spinal cord injury
Keywords:Spinal cord injury, nuclear factor erythroid 2-related factor 2, diarylpropionitrile, antioxidant, apoptosis, anti-inflammation
The initial impact of spinal cord injury (SCI) often results in inflammation leading to irreversible damage with consequent loss of locomotor function. Minimal recovery is achieved once permanent damage has occurred. Using a mouse model of SCI we observed a transitory increase followed by a rapid decline in gene expression and protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of cellular anti-oxidative genes. Immediate treatment with diarylpropionitrile (DPN), a non-steroidal selective estrogen receptor ß ligand, resulted in a significant increase in Nrf2 levels, and reduction of inflammation and apoptosis compared to untreated SCI animals. Furthermore, DPN-treatment improved locomotor function within 7 days after induction of SCI. DPN acted through activation of PI3K/ Akt pathway, known to be involved in down-regulation of apoptosis and up-regulation of cell survival in injured tissues. These findings suggest that immediate activation of cellular anti-oxidative stress mechanisms should provide protection against irreversible tissue damage and its profound detrimental effect on locomotor function associated with SCI.
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