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

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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.

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Acknowledgments

This work was supported by the following grants: National Natural Science Foundation of China (30871219, 31071048 and 81070976), China 973 Pre-program (2011CB512109), Funding Project for Academic Human Resources Development in Institutions of Higher Learning under the Jurisdiction of Beijing Municipality (PHR200906116), and Ph.D. Programs Foundation of Ministry of Education of China (20091107110001).

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Authors and Affiliations

  1. Department of Anesthesiology, Capital Medical University Affiliated Beijing Tongren Hospital, Beijing, 100730, People’s Republic of China

    Luowa Shu, Tianzuo Li, Fang Ji, Chuxiong Pan & Bingxi Zhang

  2. Department of Neurobiology and Beijing Institute for Neuroscience, Capital Medical University, #10 You An Men Wai Xi Tou Tiao, Beijing, 100069, People’s Republic of China

    Song Han & Junfa Li

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  1. Luowa Shu
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Correspondence to Bingxi Zhang or Junfa Li.

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Luowa Shu and Tianzuo Li contributed equally to this work.

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Shu, L., Li, T., Han, S. et al. Inhibition of Neuron-Specific CREB Dephosphorylation is Involved in Propofol and Ketamine-Induced Neuroprotection Against Cerebral Ischemic Injuries of Mice. Neurochem Res 37, 49–58 (2012). https://doi.org/10.1007/s11064-011-0582-3

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