Comparison of calpain and caspase activities in the adult rat brain after transient forebrain ischemia.

The role of calpain and caspase family proteases in postischemic neuronal death remains controversial. This study compared the timing, location, and relative activity of calpains and caspases in the adult rat brain following 10 min of transient forebrain ischemia. Western blots of cortical, striatal, and hippocampal homogenates demonstrated a alpha-spectrin cleavage pattern indicative of predominant calpain activity, which peaked between 24 and 48 h after reperfusion. However, immunohistochemical evidence of both caspase 3 activation and caspase-mediated substrate cleavage was detected as early as 1 h and as late as 7 days after reperfusion in circumscribed neuronal populations. Simultaneous or sequential caspase and calpain activation was also observed suggesting the potential for interaction of these protease systems. The complex spatiotemporal pattern of calpain and caspase activity observed in this study provides important insights for the development and evaluation of therapeutic strategies to reduce protease-mediated injury following global brain ischemia.