Role of tissue plasminogen activator/plasmin cascade in delayed neuronal death after transient forebrain ischemia |
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Authors: | Takahashi Hiroshi Nagai Nobuo Urano Tetsumei |
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Institution: | Department of Neurosurgery, Fujinomiya City General Hospital, Fujinomiya-shi, Shizuoka-ken 418-0076, Japan. |
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Abstract: | We studied the possible involvement of the tissue plasminogen activator (t-PA)/plasmin system on both delayed neuronal death in the hippocampus and the associated enhancement of locomotor activity in rats, after transient forebrain ischemia induced by a four-vessel occlusion (FVO). Seven days after FVO, locomotor activity was abnormally increased and, after 10 days, pyramidal cells were degraded in the CA1 region of the hippocampus. FVO increased the t-PA antigen level and its activity in the hippocampus, which peaked at 4 h. Both the enhanced locomotor activity and the degradation of pyramidal cells were significantly suppressed by intracerebroventricular injection of aprotinin, a plasmin inhibitor, at 4 h but not during FVO. These results suggest the importance of the t-PA/plasmin cascade during the early pathological stages of delayed neuronal death in the hippocampus following transient forebrain ischemia. |
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