Nonproteolytic Neuroprotection by Human Recombinant Tissue Plasminogen Activator

Science  23 Apr 1999:
Vol. 284, Issue 5414, pp. 647-650
DOI: 10.1126/science.284.5414.647

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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.

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