Neuroprotective effect of neuroserpin in rat primary cortical cultures after oxygen and glucose deprivation and tPA.

摘要

Besides its role as a thrombolytic agent, tissue plasminogen activator (tPA) triggers harmful effects in the brain parenchyma after stroke, such as inflammation, excitotoxicity and basal lamina degradation. Neuroserpin, a natural inhibitor of tPA, has shown neuroprotective effects in animal models of brain infarct. However, the molecular mechanisms of neuroserpin-mediated neuroprotection after brain ischemia remain to be well characterized. Then, our aim was to investigate such mechanisms in primary mixed cortical cell cultures after oxygen and glucose deprivation (OGD). Primary rat mixed cortical cultures containing both astrocytes and neurons were subjected to OGD for 150min and subsequently treated with either tPA (5mug/mL), neuroserpin (0.125, 0.25, 0.5 or 1muM), and tPA together with neuroserpin at the mentioned doses. Twenty-four hours after treatment, LDH release, caspase-3 activity, MCP-1, MIP-2, active MMP-9, GRO/KC and COX-2 were measured. Statistical differences were analyzed using Student's t-test or one-way ANOVA as appropriate. Treatment with tPA after OGD increased LDH release, active MMP-9, MCP-1 and MIP-2 (all p