Experimental autoimmune encephalomyelitis (EAE) is an animal model for studying 
multiple sclerosis (MS). Calpain has been implicated in many inflammatory and 
neurodegenerative events that lead to disability in EAE and MS. Thus, treating 
EAE animals with calpain inhibitors may block these events and ameliorate 
disability. To test this hypothesis, acute EAE Lewis rats were treated dose 
dependently with the calpain inhibitor calpeptin (50-250 microg/kg). Calpain 
activity, gliosis, loss of myelin, and axonal damage were attenuated by 
calpeptin therapy, leading to improved clinical scores. Neuronal and 
oligodendrocyte death were also decreased, with down-regulation of proapoptotic 
proteins, suggesting that decreases in cell death were due to decreases in the 
expression or activity of proapoptotic proteins. These results indicate that 
calpain inhibition may offer a novel therapeutic avenue for treating EAE and MS.