Ruled a Suicide?

It's only fair  to tell you that the role of  apoptosis in the setting of brain ischemia is not exactly clear. In fact, there's a certain amount of controversy about it. It's best to discuss what we know about the situation separately for focal and global brain ischemia.

Focal Ischemia: Morphological and biochemical evidence seems to suggest apoptotic death in the penumbra, with necrosis in the core.

FOCAL ISCHEMIC NEURONAL DEATH

PRO-APOPTOSIS

ANTI-APOPTOSIS

DNA laddering is observed in the penumbra within a few hours.

Necrotic phenotypes predominate in the core.

Transcription of caspase 3 is observed in vulnerable neurons.

Caspase inhibitors convert "apoptotic" phenotypes to "necrotic" phenotypes.

Activated caspase 3 is seen by 1-3 h of reperfusion.

Caspase 3 inhibitors decrease caspase cleavage products, reduce tissue damage and improve outcome in rodent stroke models.

Global Ischemia: the data is conflicting at best, with characteristics of both apoptosis and necrosis.

GLOBAL ISCHEMIC NEURONAL DEATH

PRO-APOPTOSIS

ANTI-APOPTOSIS

TUNEL staining (indicative of DNAse cleavage) observed in both animals and humans. 

Apoptotic bodies not observed by most investigators. 

Caspase inhibitors protect against neuronal death.

Morphology typical of necrosis in primate neurons, even in the face of caspase activation.

Activated caspase 3 seen as early as 1 hr of reperfusion.

Little evidence of nuclear clumping or chromatin condensation at the light level (mixed results from EM).

Caspase 3 mRNA appears early in SVNs.

PARP breaks down between 24 and 72 hours.

BAX and BclXs expressed in vulnerable CA1 neurons.

Cytochrome c translocation noted in SVNs!

 

 

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