Nonproteolytic neuroprotection by human recombinant tissue plasminogen activator.
Human recombinant tissue plasminogen activator (tPA) may benefit ischemic stroke patients by dissolving clots. However, independent of thrombolysis, tPA may also have deleterious effects on neurons by promoting excitotoxicity. Zinc neurotoxicity has been shown to be an additional key mechanism in brain injuries. Hence, if tPA affects zinc neurotoxicity, this may provide additional insights into its effect on neuronal death. Independent of its proteolytic action, tPA markedly attenuated zinc-induced cell death in cortical culture, and, when injected into cerebrospinal fluid, also reduced kainate seizure-induced hippocampal neuronal death in adult rats.
Kim
Y H
YH
National Creative Research Initiative Center for the Study of Central Nervous System Zinc and Department of Neurology, University of Ulsan College of Medicine, 388-1 Poongnap-Dong Songpa-Gu, Seoul 138-736, Korea.
Park
J H
JH
Hong
S H
SH
Koh
J Y
JY
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D019610:Cytoprotection; D005341:Fibrinolysin / Q000494:pharmacology; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000134:cerebrospinal fluid / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced / Q000473:pathology; D010959:Tissue Plasminogen Activator / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D015032:Zinc / Q000378:metabolism / Q000633:toxicity*
D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D016202:N-Methylaspartate; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D015032:Zinc; D007608:Kainic Acid