We investigated the relationship between the activity of
calcium-dependent
protease (
calpain) and the ischemic neuronal damage. We also investigated the mechanism of ischemic resistance in astrocytes. In gerbil, a 10-min forebrain
ischemia was induced by occlusion of both common carotid arteries. The
calpain-induced proteolysis of cytoskeleton (
fodrin) was examined by immunohistochemistry. Immunolocalization of micro and
m-calpain was also examined. Intact
fodrin was observed both in neurons and astrocytes, but proteolyzed
fodrin was not observed in normal brain. Fifteen minutes after
ischemia, proteolysis of
fodrin took place in putamen, parietal cortex and hippocampal CA1. The proteolysis extended to thalamus 4 h after
ischemia after which the immunoreactivity faded down in all areas except hippocampus. On day 7, the proteolysis was still observed only in hippocampus. Neurons with the proteolysis of
soma resulted in neuronal death. Throughout the experiment, the proteolysis was not observed in astrocytes. micro -
Calpain was observed only in neurons but
m-calpain was observed both in neurons and astrocytes. The
ischemia induced only micro -
calpain activation, which resulted in
fodrin proteolysis of neurons with differential spatial distribution and temporal course. The proteolysis was developed rapidly and was completed within 24 h in all vulnerable regions except hippocampal CA1. The proteolysis preceded the neuronal death. The mechanism of the proteolysis seemed to be involved by Ca(2+) influx via
glutamate receptor and rapid neuronal death seemed reasonable. The reason why neuronal death in CA1 evolved slowly was not clarified. In astrocytes,
fodrin was not proteolyzed by
m-calpain. The low Ca(2+)-sensitivity of
m-calpain may be the reason of ischemic resistance in astrocytes.