Cerebral ischemia produces laddered DNA fragments distinct from cardiac ischemia and archetypal apoptosis

The electrophoretic pattern of laddered DNA fragments which has been observ ed after cerebral ischemia is considered to indicate that neurons are dying by apoptosis. Herein the authors directly demonstrate using ligation-media ted polymerase chain reaction methods that 99% of the DNA fragments produce d after either global or focal ischemia in adult rats, or produced after hy poxia-ischemia in neonatal rats, have staggered ends with a 3' recess of ap proximately 8 to 10 nucleotides. This is in contrast to archetypal apoptosi s in which the DNA fragments are blunt ended as seen during developmental p rogrammed cell death in dying cortical neurons, neuroblastoma, or thymic ly mphocytes. It is not simply ischemia that results in staggered ends in DNA fragments because ischemic myocardium is similar to archetypal apoptosis wi th a vast majority of blunt-ended fragments. It is concluded that the endon ucleases that produce this staggered fragmentation of the DNA backbone in i schemic brain must be different than those of classic or type I apoptosis.