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Science 23 April 1999:
Vol. 284. no. 5414, pp. 647 - 650
DOI: 10.1126/science.284.5414.647
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Reports

Nonproteolytic Neuroprotection by Human Recombinant Tissue Plasminogen Activator

Yang-Hee Kim, 12 June-Hee Park, 1 Seung Hwan Hong, 2 Jae-Young Koh 1*

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.

1 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.
2 Department of Molecular Biology and Institute for Molecular Biology and Genetics, Seoul National University, Seoul, Korea.
*   To whom correspondence should be addressed. E-mail: jkko{at}www.amc.seoul.kr

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