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

Neurological Research
Jian-Guo LiCe Zhang

Abstract

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). Male Wistar rats were subjected to a sham or transient forebrain ischemia procedure. Animals received the intracerebroventricular injection of U0126 (5 μl, 0.2 μg/μl) or vehicle 30 min before ischemia. Homogenates of the hippocampal CA1 field were obtained from sham-operated and ischemic rats 6, 12 or 48 h 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. 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. 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 ther...Continue Reading

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