Effects And Mechanisms Of The Surfactant Poloxamer 188 In Excitotoxicity Mediated By NMDA Receptors

Aim: To study the neuroprotective effects and mechanisms of the surfactant poloxamer 188 in excitotoxicity mediated by NMDA receptors.Methods: Rat excitotoxic model was produced with stereotaxic administration of QA into unilateral striatum. The neuroprotective effects of P188 were detected with Nissl staining and cell counting. Protein levels of IκB-α, DRAM and LAMP-2 were determined with Western blot analysis. Some rats were pre-treated with sublingual vein injection of P188 10 min prior to intrastriatal injection of QA.Results: Nissl staining and cell counting revealed that pre-treatment with P188 significantly reduced the loss of striatal neurons and significantly reduced lesion size induced by QA (P<0.01). Western blot analysis revealed the decrease in IκB-αlevel in a time-dependent fashion, while there were increases in the protein levels of DRAM and LAMP-2 induced by QA. Pre-treatment with P188 inhibited QA-induced changes in IκB-α, DRAM, and LAMP-2 (P<0.01).Conclusions: Autophagy/lysosome-mediated apoptotic signaling pathways and NF-κB signaling pathway are involved in the excitotoxicity mediated by NMDA receptor. P188 has neuroprotective actions in against QA-induced apoptotic death of rat stritatal neurons by inhibiting autophagy/lysosome-mediated apoptotic signaling pathways and NF-κB signaling pathway.