%0 Journal Article
%T Neuroprotective Effects of Daphnetin against NMDA Receptor-Mediated Excitotoxicity
%A Le Yang
%A Qi Yang
%A Kun Zhang
%A Yu-Jiao Li
%A Yu-Mei Wu
%A Shui-Bing Liu
%A Lian-He Zheng
%A Ming-Gao Zhao
%J Molecules
%P 14542-14555
%D 2014
%I MDPI AG
%R 10.3390/molecules190914542
%X The accumulation of glutamate can excessively activate the N-methyl-d-aspartate (NMDA) receptors and cause excitotoxicity. Daphnetin (Dap), a coumarin derivative, is a protein kinase inhibitor that exhibits antioxidant and neuroprotective properties. However, little is known about the neuroprotective effects of Dap on glutamate-induced excitotoxicity. We evaluated the neuroprotective activities in the primary cultured cortical neurons against NMDA-induced excitotoxicity. Pretreatment with Dap significantly prevented NMDA-induced neuronal cell loss. Dap significantly inhibited the neuronal apoptosis by regulating balance of Bcl-2 and Bax expression. Furthermore, pretreatment of Dap reversed the up-regulation of NR2B-containing NMDA receptors and inhibited the intracellular Ca 2+ overload induced by NMDA exposure. In addition, Dap prevented cerebral ischemic injury in mice induced via a 2 h middle cerebral artery occlusion and a 24 h reperfusion in vivo. The findings suggest that Dap prevents the excitotoxicity through inhibiting the NR2B-containing NMDA receptors and the subsequent calcium overload in cultured cortical neurons.
%K daphnetin
%K excitotoxicity
%K neuron
%K apoptosis
%K calcium
%U http://www.mdpi.com/1420-3049/19/9/14542