Neural Regeneration Research ›› 2014, Vol. 9 ›› Issue (7): 749-756.doi: 10.4103/1673-5374.131581

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Regulation of extracellular signal-regulated kinase 1/2 influences hippocampal neuronal survival in a rat model of diabetic cerebral ischemia

Yaning Zhao 1, Jianmin Li 2, Qiqun Tang 1, Pan Zhang 1, Liwei Jing 1, Changxiang Chen 1, Shuxing Li 1   

  1. 1 College of Rehabilitation, Hebei United University, Tangshan, Hebei Province, China
    2 Affiliated Hospital of Hebei United University, Tangshan, Hebei Province, China
  • Received:2014-02-06 Online:2014-04-15 Published:2014-04-15
  • Contact: Yaning Zhao, College of Rehabilitation, Hebei United University, Tangshan 063000, Hebei Province, China, zyning789@126.com.
  • Supported by:

    This study was supported by the Hebei Province Natural Science Program, No. H2012401007; a grant from the foundation Key Project of Hebei Province Education Ministry, No. ZD2010106.

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Abstract:

Activation of extracellular signal-regulated kinase 1/2 has been demonstrated in acute brain ischemia. We hypothesized that activated extracellular signal-regulated kinase 1/2 can protect hippocampal neurons from injury in a diabetic model after cerebral ischemia/reperfusion. In this study, transient whole-brain ischemia was induced by four-vessel occlusion in normal and diabetic rats, and extracellular signal-regulated kinase 1/2 inhibitor (U0126) was administered into diabetic rats 30 minutes before ischemia as a pretreatment. Results showed that the number of surviving neurons in the hippocampal CA1 region was reduced, extracellular signal-regulated kinase 1/2 phosphorylation and Ku70 activity were decreased, and pro-apoptotic Bax expression was upregulated after intervention using U0126. These findings demonstrate that inhibition of extracellular signal-regulated kinase 1/2 activity aggravated neuronal loss in the hippocampus in a diabetic rat after cerebral ischemia/reperfusion, further decreased DNA repairing ability and accelerated apoptosis in hippocampal neurons. Extracellular signal-regulated kinase 1/2 activation plays a neuroprotective role in hippocampal neurons in a diabetic rat after cerebral ischemia/reperfusion.

Key words: nerve regeneration, brain injury, cerebral ischemia/reperfusion, DNA dependent protein kinase, extracellular signal-regulated kinase, Bax, apoptosis, hippocampus, neural regeneration