Phospholipase C (PLC) and related enzymes in signal transduction system are closely linked
to cellular damage in ischemic encephalopathy. This study was undertaken to elucidate the
time sequential changes of PLC isoenzymes (beta and gamma) in vulnerable areas of hippocampus
in global ischemia and infarcted area in focal infarction. Mongolian gerbils were used because
of their susceptibility to ischemic encephalopathy and divided into the following groups: the
bilateral ischemia with various reperfusion periods group, unilateral progressive ischemia group,
and focal ischemia group induced by infusion of iron particles through the femoral artery. The
changes of PLC isoenzymes were observed immunohistochemically and matched with morphological
changes. In the global ischemia with reperfusion group, the changes were most significant in
hippocampus. Sequential changes of neurons such as red neurons at an early stage progressed
to pknotic neurons at a later stage were noted with typical delayed neuronal damage in the
corns ammonis (CA) 1 subfield of hippocampus. Red neurons and pyknotic neurons as well as
intracytoplasmic inclusion in 3 to 24 hours of reperfusion showed loss of PLC isoenzymes as
well as tubulin. The changes of PLC expression were corresponding to the degeneration of
neurons with no discernible time sequential changes in remaining neurons. In the unilateral
hemispheric progressive ischemia group, ischemic damage was far more marked and extensive with
no selective injury pattern according to time and location. At 1 day, there was diffuse
vacuolization and necrosis of neuropil with a loss of neuron. Admixed surviving neurons and
vacuolated neuropil showed increased reaction to anti-PLC antibodies, which could be either
an evidence of protein synthesis responding to ischemic insult or an artifactual change. Focal
ischemia group showed time sequential changes of blood vessels and white blood cells with
necrosis of surrounding tissue. Degenerating hippocampal neurons in infarction also showed a
strong positive reaction to anti-PLC antibody, which was most likely due to condensation of
cytoplasm rather than increased synthesis. This study showed different changes of PLC expression
in global ischemic encephalopathy with reperfusion, progressive ischemia, and focal infarction,
which suggested different pathophysiologic mechanism between these conditions.
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