INDUCTION OF PLASMINOGEN IN RAT HIPPOCAMPAL PYRAMIDAL NEURONS BY KAINIC ACID

Tissue plasminogen activator (tPA) is used to treat acute stroke, but tPA- and plasminogen-gene-deficient mice exhibit resistance to neurode generation. Thus, it is unclear whether the tPA-plasminogen system, an extracellular proteolytic cascade plays a helpful or harmful role, an d whether plasminogen is induced by neurodegeneration. In the CA3, kai nic acid (KA)-injection caused neuronal damage after 6 h, and almost a ll of the neurons were lost after 7 days. Plasminogen mRNA was strongl y induced 6 h after injection, then gradually decreased, and was very weak at 2 days after injection. Plasminogen protein was expressed afte r 6 h and localized in abnormally shaped neurons. The in vivo expressi on of plasminogen was synchronous with morphological changes in neuron s. These results suggest that the expression of plasminogen induced by KA-injection may disrupt of neuron-extracellular matrix interaction a nd thereby contribute to cell death in neurons in the hippocampus. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved