Original article: NEUROPROTECTION BY DIARYLPROPIONITRILE IN MICE WITH SPINAL CORD INJURY

The initial impact of spinal cord injury (SCI) often results in inflammation leading to irre-versible 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. Imme-diate treatment with diarylpropionitrile (DPN), a non-steroidal selective estrogen receptor β ligand, resulted in a significant increase in Nrf2 levels, and reduction of inflammation and apoptosis compared to untreated SCI animals. Furthermore, DPN-treatment improved loco-motor 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