U0126 protects hippocampal CA1 neurons against forebrain ischemia-induced apoptosis via the ERK1/2 signaling pathway and NMDA receptors

作者：Li, Jianguo^*; Yan, Deping; Liu, Xiaoyan; Wang, Ye; Zhao, Xin; Zhang, Yu; Zhang, Ce

来源：Neurological Research, 2018, 40(4): 318-323.

DOI：10.1080/01616412.2018.1441693

• ERK1/2
• U0126
• NMDA receptor
• ischemia
• neuroprotection

Objective: Cerebral ischemia can trigger the ERK1/2 signaling cascade that enables the brain to adapt to ischemic injury. However, the mechanism of ERK1/2 in ischemic brain injury remains unclear. The aim of this study was to examine the roles of the ERK1/2 signaling pathway and NMDA receptors in the apoptosis of CA1 pyramidal neurons after ischemia/reperfusion (I/R). @@@ Methods: Male Wistar rats were subjected to a sham or transient forebrain ischemia procedure. Animals received the intracerebroventricular injection of U0126 (5 mu l, 0.2 mu g/mu l) or vehicle 30 min before ischemia. Homogenates of the hippocampal CA1 field were obtained from sham-operated and ischemic rats 6, 12 or 48h after ischemia/reperfusion (n = 6 per group) and then subjected to Western blotting analysis and TUNEL staining. Caspase-3 activity was assayed with a colorimetric assay kit. @@@ Results: We found that the phosphorylation level of ERK1/2 is increased in the CA1 region following transient I/R. Blocking the ERK1/2 signaling pathway by administration U0126 attenuated apoptotic neuronal cell death via inhibition of NMDA receptors. @@@ Conclusion: These findings suggest a novel mechanism by which the ERK1/2 signaling pathway affects the post-I/R apoptosis of CA1 pyramidal neurons, which will provide a therapeutic target for the treatment of stroke.

• 出版日期2018
• 单位山西医科大学