Remember at the beginning when I told you about the difference between apoptosis and necrosis? How necrosis was the core and the apoptosis was the penumbra? How necrosis was calpain and apoptosis was caspase? How necrosis was a meltdown and apoptosis was regulated?

Well, I have a confession to make.

I'm not sure I really believe all of that--especially in the face of the data I just summarized on the previous page. I think it may be misleading to focus on a strict dichotomy between apoptosis and necrosis. And I'm not convinced that necrosis is entirely unregulated, or that apoptosis is as tightly controlled as the "programmed cell death" terminology would lead one to suspect.

For one thing, it should be clear to you by now that ischemia can result in process that are characteristic of both classic apoptosis and classic necrosis.  Moreover, we now know that calpain can cleave caspases, and that DNA laddering can occur in the absence of caspase activity. In short, the line between apoptosis and necrosis can get pretty blurry--especially when one is talking about brain ischemia, because in brain ischemia we see a range of death phenotypes, with elements of both.