In this study, we investigated the effects of different concentration of propofol on cell viability of hippocampal neurons and explored the possible mechanism.
Patients and methods
Primary hippocampal neurons were cultured in vitro and treated with different concentration of propofol. MTT was used to examine the survival of neurons. Flow cytometry was used to detect the neuronal apoptosis. Western-blot analysis was used to examine the expression level of p-p38MAPK and p38MAPK.
We found that low concentration propofol (0.5 μM and 1 μM) promoted the cell survival rate; however, high concentration of propofol (10 μM,50 μM,100 μM,150 μM, and 200 μM) decreased the cell survival rate (P < 0.05). Flow cytometry showed that the neuronal apoptosis rate was decreased in 1 μM propofol group (P < 0.05), but was significantly higher in10μM, 100 μM and 200 μM groups in a concentration-dependent manner (P < 0.05 or P < 0.01). Western blot revealed that the propofol induced the phosphorylation of p38MAPK concentration-dependently and time-dependently. SB203580, one inhibitor of p38MAPK, increased the cell survival rate and decreased the cell apoptosis induced by high concentration of propofol.
Low concentration of propofol improved the survival rate of neurons, while high concentration of propofol promoted the cell apoptosis and decreased the cell viability. p38MAPK pathway is involved the effect of high concentration of propofol promoted on primary hippocampal neurons viability and apoptosis.
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Olney JW (2002) New insights and new issues in developmental neurotoxicology. Neurotoxicology 23:659–668
Sprung J, Flick RP, Katusic SK, Colligan RC, Barbaresi WJ, Bojanic K, Welch TL, Olson MD, Hanson AC, Schroeder DR, Wilder RT, Warner DO (2012) Attention-deficit/hyperactivity disorder after early exposure to procedures requiring general anesthesia Mayo Clinic proceedings 87:120–129
Flick RP, Katusic SK, Colligan RC, Wilder RT, Voigt RG, Olson MD, Sprung J, Weaver AL, Schroeder DR, Warner DO (2011) Cognitive and behavioral outcomes after early exposure to anesthesia and surgery. Pediatrics 128:e1053–e1061
Loepke AW, Soriano SG (2008) An assessment of the effects of general anesthetics on developing brain structure and neurocognitive function. Anesth Analg 106:1681–1707
Brenner L, Kettner SC, Marhofer P, Latzke D, Willschke H, Kimberger O, Adelmann D, Machata AM (2010) Caudal anaesthesia under sedation: a prospective analysis of 512 infants and children. Br J Anaesth 104:751–755
Istaphanous GK, Loepke AW (2009) General anesthetics and the developing brain. Curr Opin Anaesthesiol 22:368–373
Karmarkar SW, Bottum KM, Tischkau SA (2010) Considerations for the use of anesthetics in neurotoxicity studies. Comp Med 60:256–262
Fredriksson A, Ponten E, Gordh T, Eriksson P (2007) Neonatal exposure to a combination of N-methyl-D-aspartate and gamma-aminobutyric acid type A receptor anesthetic agents potentiates apoptotic neurodegeneration and persistent behavioral deficits. Anesthesiology 107:427–436
Fibuch EE, Wang JQ (2007) Inhibition of the MAPK/ERK cascade: a potential transcription-dependent mechanism for the amnesic effect of anesthetic propofol. Neurosci Bull 23:119–124
Bercker S, Bert B, Bittigau P, Felderhoff-Muser U, Buhrer C, Ikonomidou C, Weise M, Kaisers UX, Kerner T (2009) Neurodegeneration in newborn rats following propofol and sevoflurane anesthesia. Neurotox Res 16:140–147
Schifilliti D, Grasso G, Conti A, Fodale V (2010) Anaesthetic-related neuroprotection: intravenous or inhalational agents? CNS drugs 24:893–907
Fath T, Ke YD, Gunning P, Gotz J, Ittner LM (2009) Primary support cultures of hippocampal and substantia nigra neurons. Nat Protoc 4:78–85
Li Z, Liu P, Zhang H, Zhao S, Jin Z, Li R, Guo Y, Wang X (2017) Role of GABAB receptors and p38MAPK/NF-kappaB pathway in paclitaxel-induced apoptosis of hippocampal neurons. Pharm Biol 55:2188–2195
Wei M, Zhang K, Li Z, Yang P, Zhang J, Liu H (2017) Pyruvate attenuates the injury of PC12 cells induced by hypoxia via inhibiting p38MAPK phosphorylation. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 33:1191–1195
Adembri C, Venturi L, Tani A, Chiarugi A, Gramigni E, Cozzi A, Pancani T, De Gaudio RA, Pellegrini-Giampietro DE (2006) Neuroprotective effects of propofol in models of cerebral ischemia: inhibition of mitochondrial swelling as a possible mechanism. Anesthesiology 104:80–89
Adembri C, Venturi L, Pellegrini-Giampietro DE (2007) Neuroprotective effects of propofol in acute cerebral injury. CNS Drug Rev 13:333–351
Ferreira DA, Nunes CS, Antunes L, Lobo F, Amorim P (2006) Practical aspects of the use of target controlled infusion with remifentanil in neurosurgical patients: predicted cerebral concentrations at intubation, incision and extubation. Acta Anaesthesiol Belg 57:265–270
Sall JW, Stratmann G, Leong J, Woodward E, Bickler PE (2012) Propofol at clinically relevant concentrations increases neuronal differentiation but is not toxic to hippocampal neural precursor cells in vitro. Anesthesiology 117:1080–1090
Hudson AE, Hemmings HC Jr (2011) Are anaesthetics toxic to the brain? Br J Anaesth 107:30–37
Vutskits L, Gascon E, Tassonyi E, Kiss JZ (2005) Clinically relevant concentrations of propofol but not midazolam alter in vitro dendritic development of isolated gamma-aminobutyric acid-positive interneurons. Anesthesiology 102:970–976
Wu GJ, Chen WF, Hung HC, Jean YH, Sung CS, Chakraborty C, Lee HP, Chen NF, Wen ZH (2011) Effects of propofol on proliferation and anti-apoptosis of neuroblastoma SH-SY5Y cell line: new insights into neuroprotection. Brain Res 1384:42–50
Harding SJ, Browne GJ, Miller BW, Prigent SA, Dickens M (2010) Activation of ASK1, downstream MAPKK and MAPK isoforms during cardiac ischaemia. Biochim Biophys Acta 1802:733–740
Savage MJ, Lin YG, Ciallella JR, Flood DG, Scott RW (2002) Activation of c-Jun N-terminal kinase and p38 in an Alzheimer's disease model is associated with amyloid deposition. J Neurosci 22:3376–3385
Riewpaiboon A, Nuchprayoon I, Torcharus K, Indaratna K, Thavorncharoensap M, Ubol BO (2010) Economic burden of beta-thalassemia/Hb E and beta-thalassemia major in Thai children BMC research notes 3:29
Wu XJ, Zheng YJ, Cui YY, Zhu L, Lu Y, Chen HZ (2007) Propofol attenuates oxidative stress-induced PC12 cell injury via p38 MAP kinase dependent pathway. Acta Pharmacol Sin 28:1123–1128
Wei L, Matsumoto H, Yamaguchi H (2013) Propofol attenuates lipopolysaccharide-induced monocyte chemoattractant protein-1 production through p38 MAPK and SAPK/JNK in alveolar epithelial cells. J Anesth 27:366–373
Tang J, Chen X, Tu W, Guo Y, Zhao Z, Xue Q, Lin C, Xiao J, Sun X, Tao T, Gu M, Liu Y (2011) Propofol inhibits the activation of p38 through up-regulating the expression of annexin A1 to exert its anti-inflammation effect. PLoS One 6:e27890
Wu KC, Yang ST, Hsia TC, Yang JS, Chiou SM, Lu CC, Wu RS, Chung JG (2012) Suppression of cell invasion and migration by propofol are involved in down-regulating matrix metalloproteinase-2 and p38 MAPK signaling in A549 human lung adenocarcinoma epithelial cells. Anticancer Res 32:4833–4842
Fujian Provincial Department of Finance Special Fund (Funding no. 2012B014).
Fujian Medical University Professional Fund (Funding no. JS12004).
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Xu, X., Wu, G., Liu, Y. et al. Effects of propofol on hippocampal neuron viability. Childs Nerv Syst 36, 1995–2002 (2020). https://doi.org/10.1007/s00381-020-04548-z
- Hippocampal neuron
- Cell viability