Role of tissue plasminogen activator/plasmin cascade in delayed neuronal death after transient forebrain ischemia.
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.
Takahashi
Hiroshi
H
Department of Neurosurgery, Fujinomiya City General Hospital, Fujinomiya-shi, Shizuoka-ken 418-0076, Japan.
Nagai
Nobuo
N
Urano
Tetsumei
T
D000818:Animals; D017209:Apoptosis; D005341:Fibrinolysin / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D016548:Prosencephalon / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin