Effect of Polydeoxyribonucleotide on Lipopolysaccharide and Sevoflurane-Induced Postoperative Cognitive dysfunction in Human Neuronal SH-SY5Y Cells

Abstract

Purpose Postoperative cognitive dysfunction (POCD) is a complication of surgery characterized by acute cognitive dysfunction, memory impairment, and loss of attention. The effect of polydeoxyribonucleotide (PDRN) on the POCD environment induced by lipopolysaccharide (LPS) and sevoflurane exposure were investigated in human neuronal SH-SY5Y cells. Methods The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and WST-8 assays were performed to determine cell viability. Cyclic adenosine-3,5′-monophosphate (cAMP), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 concentrations were measured using enzyme-linked immunoassay (ELISA). Immunocytochemistry was performed for vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF), and western blotting for TNF-α, IL-1β, IL-6, and cAMP response element-binding protein (CREB). Results Induction of the POCD environment reduced cell viability in the MTT and WST-8 assays. PDRN treatment reduced TNF-α, IL-1β, and IL-6 expression in POCD conditions, and significantly increased cAMP concentrations and the p-CREB/CREB ratio. PDRN treatment activated adenosine A2A receptors and then increased the expression of VEGF and BDNF, which had been reduced by LPS and sevoflurane exposure. Conclusions PDRN treatment showed a therapeutic effect on the LPS and sevoflurane-induced POCD environment. PDRN was shown to have an excellent therapeutic effect on POCD, not only by promoting rapid anti-inflammatory effects in damaged cells, but also by enhancing the expression of BDNF and VEGF.

Keywords

• postoperative cognitive dysfunction
• polydeoxyribonucleotides
• pro-inflammatory cytokine