Propofol inhibits proliferation and induces neuroapoptosis of hippocampal neurons in vitro via downregulation of NF‐κB p65 and Bcl‐2 and upregulation of caspase‐3

Abstract

Propofol is widely used in paediatric anaesthesia and intensive care unit because of its essentially short-acting anaesthetic effect. Recent data have shown that propofol induced neurotoxicity in developing brain. However, the mechanisms are not extremely clear. To gain a better insight into the toxic effects of propofol on hippocampal neurons, we treated cells at the days in vitro 7 (DIV 7), which were prepared from Sprague-Dawley embryos at the 18th day of gestation, with propofol (0.1-1000 μM) for 3 h. A significant decrease in neuronal proliferation and a remarkable increase in neuroapoptosis were observed in DIV 7 hippocampal neurons as measured by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay and apoptosis assay respectively. Moreover, propofol treatment decreased the nuclear factor kappaB (NF-κB) p65 expression, which was accompanied by a reduction in B-cell lymphoma 2 (Bcl-2) mRNA and protein levels, increased caspase-3 mRNA and activation of caspase-3 protein. These results indicated that downregulation of NF-κB p65 and Bcl-2 were involved in the potential mechanisms of propofol-induced neurotoxicity. This likely led to the caspase-3 activation, triggered apoptosis and inhibited the neuronal growth and proliferation that we have observed in our in vitro systems.

Dexmedetomidine attenuates the propofol-induced long-term neurotoxicity in the developing brain of rats by enhancing the PI3K/Akt signaling pathway

“…Our previous studies have demonstrated that propofol induced acute neurotoxicity in young rats and Dex attenuated the propofol-induced neuroapoptosis by enhancing the Akt activation in a dose-dependent manner 28,39. In our study, excluding the effect of hypoxia and hypercapnia on the development of brain, the results indicated that propofol injected into young rats induced neurotoxicity, leading to impairment of spatial learning and memory in their adult age.…”

“…Previous studies have suggested that propofol-induced neuronal toxicity is associated with increased levels of TNF-α in the developing brain and increases intracellular free calcium by activating the GABA A receptor and subsequent opening of the L-type voltage-gated calcium channels 4,44. Our previous studies have shown that induction of hippocampal neuron apoptosis is associated with decrease of the NF-κB and Bcl-2 expression in vitro and inhibition of the PI3K/Akt signaling pathway in the hippocampus of rats 28,39. Activation of the PI3K/Akt signaling can promote neuronal survival and synaptic plasticity 45.…”

Propofol Prevents Renal Ischemia-Reperfusion Injury via Inhibiting the Oxidative Stress Pathways

“…But it was reported that propofol induced apoptosis of hippocampal neurons in vitro via down-regulation of NF-κB p65 and Bcl-2 and up-regulation of caspase-3. The controversial effect of propofol on apoptosis in different tissues may be due to the specificity of cell types or the conditions of propofol treatment [52].…”

Astaxanthin reduces isoflurane-induced neuroapoptosis via the PI3K/Akt pathway

“…Isoflurane interferes with the formation of neuronal networks during the developmental process to hinder the maturation and differentiation of neurons (19). The effect of inhalation anesthetics on the developing nervous system is not limited to neural degeneration and induced neuroapoptosis (20). Other mechanisms are involved in the toxic isoflurane-induced effect.…”