title: Inhibition of neuron-specific CREB dephosphorylation is involved in propofol and ketamine-induced neuroprotection against cerebral ischemic injuries of mice.
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.
authors: Department of Anesthesiology, Capital Medical University Affiliated Beijing Tongren Hospital, Beijing 100730, People's Republic of China.
authors: Luowa
authors: L
authors: Shu
authors: Tianzuo
authors: T
authors: Li
authors: Song
authors: S
authors: Han
authors: Fang
authors: F
authors: Ji
authors: Chuxiong
authors: C
authors: Pan
authors: Bingxi
authors: B
authors: Zhang
authors: Junfa
authors: J
authors: Li
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002545:Brain Ischemia / Q000517:prevention & control*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation; D015742:Propofol / Q000494:pharmacology*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D018696:Neuroprotective Agents; D007649:Ketamine; D015742:Propofol