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

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.

[1]  Y. Cho,et al.  Treadmill exercise and wheel exercise improve motor function by suppressing apoptotic neuronal cell death in brain inflammation rats , 2018, Journal of exercise rehabilitation.

[2]  N. Kotekar,et al.  Postoperative cognitive dysfunction – current preventive strategies , 2018, Clinical interventions in aging.

[3]  N. Sabri,et al.  Ameliorative Effects of α-Tocopherol and/or Coenzyme Q10 on Phenytoin-Induced Cognitive Impairment in Rats: Role of VEGF and BDNF-TrkB-CREB Pathway , 2018, Neurotoxicity Research.

[4]  Azeem Alam,et al.  Surgery, neuroinflammation and cognitive impairment , 2018, EBioMedicine.

[5]  Wei Liu,et al.  Inflammation caused by peripheral immune cells across into injured mouse blood brain barrier can worsen postoperative cognitive dysfunction induced by isoflurane , 2018, BMC Cell Biology.

[6]  A. Bitto,et al.  Neuroprotective Effects of Polydeoxyribonucleotide in a Murine Model of Cadmium Toxicity , 2018, Oxidative medicine and cellular longevity.

[7]  Chang-Ju Kim,et al.  Combination therapy with polydeoxyribonucleotide and proton pump inhibitor enhances therapeutic effectiveness for gastric ulcer in rats , 2018, Life sciences.

[8]  B. Peng,et al.  The postoperative effect of sevoflurane inhalational anesthesia on cognitive function and inflammatory response of pediatric patients. , 2018, European review for medical and pharmacological sciences.

[9]  Jun-Jang Jin,et al.  Treadmill exercise with bone marrow stromal cells transplantation facilitates neuroprotective effect through BDNF-ERK1/2 pathway in spinal cord injury rats , 2018, Journal of exercise rehabilitation.

[10]  Chang-Ju Kim,et al.  Late starting treadmill exercise improves spatial leaning ability through suppressing CREP/BDNF/TrkB signaling pathway following traumatic brain injury in rats , 2018, Journal of exercise rehabilitation.

[11]  Yue Liu,et al.  Emerging Roles of Immune Cells in Postoperative Cognitive Dysfunction , 2018, Mediators of inflammation.

[12]  Hong Ning,et al.  Hispidulin prevents sevoflurane- Induced memory dysfunction in aged rats. , 2017, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[13]  L. Birder,et al.  Current Pharmacologic Approaches in Painful Bladder Research: An Update , 2017, International neurourology journal.

[14]  D. Bryden,et al.  Postoperative cognitive dysfunction and dementia: what we need to know and do , 2017, British journal of anaesthesia.

[15]  Jongki Hong,et al.  Dexmedetomidine Oral Mucosa Patch for Sedation Suppresses Apoptosis in Hippocampus of Normal Rats , 2017, International neurourology journal.

[16]  Seyeon Park,et al.  Phosphoproteome Profiling of SH-SY5y Neuroblastoma Cells Treated with Anesthetics: Sevoflurane and Isoflurane Affect the Phosphorylation of Proteins Involved in Cytoskeletal Regulation , 2016, PloS one.

[17]  D. Rombo,et al.  BDNF-induced presynaptic facilitation of GABAergic transmission in the hippocampus of young adults is dependent of TrkB and adenosine A2A receptors , 2016, Purinergic Signalling.

[18]  Heng Yan,et al.  Postoperative cognitive dysfunction after inhalational anesthesia in elderly patients undergoing major surgery: the influence of anesthetic technique, cerebral injury and systemic inflammation , 2015, BMC Anesthesiology.

[19]  G. Yan,et al.  Serum CRP and urinary trypsin inhibitor implicate postoperative cognitive dysfunction especially in elderly patients , 2015, The International journal of neuroscience.

[20]  X. Gu,et al.  Plasma levels of tumor necrosis factor-α in adolescent idiopathic scoliosis patients serve as a predictor for the incidence of early postoperative cognitive dysfunction following orthopedic surgery , 2015, Experimental and therapeutic medicine.

[21]  J. Cha,et al.  Adenosine A2A-receptor agonist polydeoxyribonucleotide promotes gastric ulcer healing in Mongolian gerbils , 2014 .

[22]  M. Maze,et al.  The neuroinflammatory response of postoperative cognitive decline. , 2013, British medical bulletin.

[23]  M. Ji,et al.  Changes in plasma and cerebrospinal fluid biomarkers in aged patients with early postoperative cognitive dysfunction following total hip-replacement surgery , 2013, Journal of Anesthesia.

[24]  Y. Liu,et al.  Postoperative Cognitive Dysfunction is Correlated with Urine Formaldehyde in Elderly Noncardiac Surgical Patients , 2012, Neurochemical Research.

[25]  A. Bitto,et al.  Polydeoxyribonucleotide reduces cytokine production and the severity of collagen-induced arthritis by stimulation of adenosine A(₂A) receptor. , 2011, Arthritis and rheumatism.

[26]  J. Cheong,et al.  Activation of Adenosine A2A Receptor Up-Regulates BDNF Expression in Rat Primary Cortical Neurons , 2011, Neurochemical Research.

[27]  A. Bitto,et al.  Activation of adenosine A2A receptors by polydeoxyribonucleotide increases vascular endothelial growth factor and protects against testicular damage induced by experimental varicocele in rats. , 2011, Fertility and sterility.

[28]  M. Maze,et al.  Role of interleukin‐1β in postoperative cognitive dysfunction , 2010, Annals of neurology.

[29]  A. Bitto,et al.  Polydeoxyribonucleotide (PDRN): a safe approach to induce therapeutic angiogenesis in peripheral artery occlusive disease and in diabetic foot ulcers. , 2009, Cardiovascular & hematological agents in medicinal chemistry.

[30]  J. F. Chen,et al.  Adenosine A2A receptors are required for normal BDNF levels and BDNF‐induced potentiation of synaptic transmission in the mouse hippocampus , 2007, Journal of neurochemistry.

[31]  Pál Pacher,et al.  Adenosine receptors: therapeutic aspects for inflammatory and immune diseases , 2006, Nature Reviews Drug Discovery.

[32]  Z. Wang,et al.  Intravesical Escherichia coli lipopolysaccharide stimulates an increase in bladder nerve growth factor , 2001, BJU international.

[33]  B. Fredholm Adenosine receptors. , 1982, Medical biology.