After an ischemic insult, calpain is like one of those white supremacy biker dudes on an overdose of meth. He goes insane and starts tweaking on all kinds of molecules.  When we look at some of the targets of calpain, we're going to see, again, how the Four Horsemen are interconnected--that is, how apparently different pathological processes have a robust cross-talk that makes it extremely difficult, if not impossible, to really separate them.

Translation inititation factors: Calpain is known to cleave the translation initiation factors eIF4G and eIF4E. This damage results in changes in "message selection," exacerbating the damage caused by the arrest in protein synthesis.

Spectrin and other structural molecules: This is a natural, since calpain is so intimately involved in cytoskeletal remodeling. But when calpain goes bonkers, its affinity for the cytoskeleton can obviously be disastrous.

Procaspases: Calpain is known to cleave a number of procaspaces. These are proteases which, as we shall see, are critical for the execution of apoptosis ("cell suicide").

Bax: Calpain can cleave this pro-apoptotic molecule, yielding a fragment that is even more pro-apoptotic.

Figure. Our story continues. We've already seen how calcium spill during ischemia leads to oxidative stress. Now we see that it also leads to calpain craziness.