Dexmedetomidine pretreatment attenuates propofol-induced neurotoxicity in neuronal cultures from the rat hippocampus

Abstract

Propofol is widely used for the induction and maintenance of pediatric anesthesia. Previous studies have indicated that propofol can induce apoptosis, and damage cognitive and memory functions. Dexmedetomidine is a potent α-2 adrenoceptor agonist with high selectivity. Previous observations have shown that dexmedetomidine exhibits anti-apoptotic qualities. The present study evaluated the neuroprotective effects of dexmedetomidine pretreatment against propofol-induced neurotoxicity in immature hippocampal neurons. The viability and apoptotic rate of the neurons were detected using a Cell Counting Kit-8 assay and flow cytometry. The mRNA and protein expression levels of brain-derived neurotrophic factor (BDNF), B-cell lymphoma-2 (Bcl-2) and phosphorylated-cyclic-AMP response element binding protein (p-CREB) were detected using semiquantitative reverse transcription-polymerase chain reaction and western blot analyses, respectively. These results showed that propofol exposure (100 μM; 3 h) reduced neuronal viability, induced cell apoptosis and decreased the expression levels of BDNF, Bcl-2 and p-CREB. Dexmedetomidine treatment (0.001-100 μM) of the neurons prior to propofol exposure attenuated the propofol-induced neuronal apoptosis and increased expression levels of BDNF, Bcl-2 and p-CREB compared with the propofol only group. In addition, dexmedetomidine at the highest concentration provided superior neuroprotection of neurons. These in vitro data indicated that dexmedetomidine exerted direct neuroprotective effects to prevent cultured hippocampal neuronal injury caused by propofol, accompanied by an increase in the levels of p-CREB, Bcl-2 and BDNF.