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: Luowa Shu, Tianzuo Li, Song Han, Fang Ji, Chuxiong Pan, Bingxi Zhang, Junfa Li
• Journal: Neurochemical research (Neurochem Res) Vol. 37 Issue 1 Pg. 49-58 (Jan 2012) ISSN: 1573-6903 [Electronic] United States
• PMID: 21892690 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclic AMP Response Element-Binding Protein
• Neuroprotective Agents
• Ketamine
• Propofol

Topics

• Animals
• Blotting, Western
• Brain Ischemia (prevention & control)
• Cyclic AMP Response Element-Binding Protein (metabolism)
• Electrophoresis, Polyacrylamide Gel
• Ketamine (pharmacology)
• Male
• Mice
• Mice, Inbred BALB C
• Neuroprotective Agents (pharmacology)
• Phosphorylation
• Propofol (pharmacology)