Delayed neuronal demage in CA1 of hippocampus may be an
apoptosis-necrosis continuum in rabbit following global cerebral ischemia
He YX2,
Fan XM1, Qian SY1, Shen HQ1
1Beijing Children’s Hospital, Beijing,
China
2Hebei Children’s Hospital, Shijiazhuang,
China
Objective: To investigate the
relationship between DNA fragmentation and ultrastructure of delayed
neuronal damage following global cerebral ischemia in rabbit.
Methods: 36 rabbits were randomly divided into any one of the following
six groups: sham-operated, ischemic 1, 2, 3, 5, and 7day groups (n=6 for
each group). 30 minutes global cerebral ischemia was induced by 4-vessel
occlusion. Rabbits of each group were reanesthesized at set times and the
brains were fixed by transcardial perfusion for TUNEL and ultrastructural
examination by electron microscope.
Results: Ischemia induced significant TUNEL positive reactions in
neurons in CA1 area of hippocampus at 1 day after reperfusion, compared
with sham-operated group, P=0.000. The number of TUNEL positive neurons was
gradually increased with time, but there was not statistical significance
among ischemic 1 to 5-day groups. Those in 7-day group were significantly
more than those in any other groups; P=0.000. On electron microscope
examination, both features of necrosis and apoptosis, such as swollen
mitochondria and condensation of chromatin, were found in damaged neurons
in CA1, but no apoptotic body were observed. The extent of neuronal damage
consistent with TUNEL positive reactions.
Conclusions: Apoptosis and necrosis
may not be mutually exclusive modes of delayed ischemic neuronal death and
may be continuum of both.