PrPC expression and calpain activity independently mediate the effects of closed head injury in mice

CHI-induced calpain activation resulted in breakdown products (BDPs) of αII-spectrin (SBDPs) and GFAP (GBDP-44 K) in all brain regions and mouse lines. CHI caused significant increases in SBDP145, GFAP and GBDP-44 K when compared to sham. With few exceptions, the calpain inhibitor, SNJ-1945, reduced SBDP145 and GBDP-44 K levels. Behavioral studies suggested that PrPC and calpain independently affect learning and memory. Overall, we conclude that: (i) there is SNJ-1945-sensitive calpain activation in both neuron and glial cells following CHI, (ii) closed head trauma is not affected by, nor does it have an influence on, PrPC expression, and (iii) PrPC expression plays a minor role, if any, in CHI-induced calpain activation in vivo.