Neurochemical Research

, Volume 37, Issue 1, pp 49–58

Inhibition of Neuron-Specific CREB Dephosphorylation is Involved in Propofol and Ketamine-Induced Neuroprotection Against Cerebral Ischemic Injuries of Mice

Authors

  • Luowa Shu
    • Department of AnesthesiologyCapital Medical University Affiliated Beijing Tongren Hospital
  • Tianzuo Li
    • Department of AnesthesiologyCapital Medical University Affiliated Beijing Tongren Hospital
  • Song Han
    • Department of Neurobiology and Beijing Institute for NeuroscienceCapital Medical University
  • Fang Ji
    • Department of AnesthesiologyCapital Medical University Affiliated Beijing Tongren Hospital
  • Chuxiong Pan
    • Department of AnesthesiologyCapital Medical University Affiliated Beijing Tongren Hospital
    • Department of AnesthesiologyCapital Medical University Affiliated Beijing Tongren Hospital
    • Department of Neurobiology and Beijing Institute for NeuroscienceCapital Medical University
Original Paper

DOI: 10.1007/s11064-011-0582-3

Cite this article as:
Shu, L., Li, T., Han, S. et al. Neurochem Res (2012) 37: 49. doi:10.1007/s11064-011-0582-3

Abstract

Propofol and ketamine may provide certain degree of neuroprotection, but the underlying mechanism remains unclear to date. The cAMP response element-binding protein (CREB) was proposed that its phosphorylation at Ser133 (P-CREB) constituted a convergence point involved in neuroprotection. The purpose of this study was to determine whether different dosages of propofol and ketamine could provide neuroprotection against permanent middle cerebral artery occlusion (MCAO)-induced ischemic injuries and the involvement of P-CREB. Eighty adult male BALB/c mice that underwent 6 h MCAO were randomly divided into eight groups: Sham-operation; MCAO + saline; MCAO + 25, 50, 100 mg/kg propofol; and MCAO + 25, 50, 100 mg/kg ketamine (intraperitoneal injection 30 min following MCAO). We found that 50, 100 (not 25) mg/kg propofol, and 25 (not 50 and 100) mg/kg ketamine could significantly reduce the infarct volume, edema ratio and neurological deficit (n = 10 per group) as well as inhibit the decrease of P-CREB level in peri-infarct region when compared with that of MCAO + saline group (n = 6 per group). In addition, the results of double-labeled immunofluorescent staining showed that P-CREB co-localized with neuron-specific marker, NeuN, in the peri-infarct region of 50 mg/kg propofol and 25 mg/kg ketamine treated 6 h MCAO mice (n = 4 per group). These results suggested that inhibition of neuron-specific P-CREB dephosphorylation in the peri-infarct region is involved in high dose propofol and low dose ketamine-induced neuroprotection of 6 h MCAO mice.

Keywords

PropofolKetamineMCAOCREBNeuN

Copyright information

© Springer Science+Business Media, LLC 2011