Role of NMDA Receptor in Central Nervous System Injury of Obstructive Jaundice_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 ZHANGLi-chao ¹ , CAOHui-fang ¹ , WANGChen-yu ² , ZHOUYuan-long ¹ ,  LIUHuai-jun ³

1. Minimally Invasive Biliary Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China;
2. Medical Department, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei Province, China;
3. Department of Radiology, The Second Affiliated Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China;

Corresponding author：

LIUHuai-jun, Email: rockboyyu@126.com

Keywords：

Obstructive jaundice; Hyperbilirubinemia; N-methyl-D-aspartate receptor; Central nervous system

DOI：

10.7507/1007-9424.20150268

Video：

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Objective To evaluate the role of N-methyl-D-aspartate (NMDA) receptor in central nervous system (CNS) injury of obstructive jaundice. Method The related literatures about NMDA receptor and the CNS injury caused by hyperbilirubinemia were retrieved and reviewed. Results The CNS injury of obstructive jaundice was related to overactivation of NMDA receptor, which finally resulted in degeneration and necrosis of nerve cells. The NMDA receptor antagonist MK-801 could relieve the CNS injury of obstructive jaundice. Conclusions NMDA receptor plays an important role in the CNS injury caused by hyperbilirubinemia, and the blocker of NMDA receptor has protective effects in this process. However, there is no report of MK-801 in clinical application when hyperbilirubinemia happened.

Citation： ZHANGLi-chao, CAOHui-fang, WANGChen-yu, ZHOUYuan-long, LIUHuai-jun. Role of NMDA Receptor in Central Nervous System Injury of Obstructive Jaundice. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2015, 22(8): 1023-1027. doi: 10.7507/1007-9424.20150268 Copy

1.	Qin LX, Tang ZY. Hepatocellular carcinoma with obstructive jaun-dice:diagnosis, treatment and prognosis. World J Gastroenterol, 2003, 9(3):385-391.
2.	Iskander I, Gamaleldin R, El Houchi S, et al. Serum bilirubin and bilirubin/albumin ratio as predictors of bilirubin encephalopathy. Pediatrics, 2014, 134(5):e1330-e1339.
3.	Diamond I, Schmid R. The pathogenesis of bilirubin encephalopathy:experimental models in newborn and adult animals. Trans Am Neurol Assoc, 1965, 90:38-41.
4.	Song S, Hu Y, Gu X, et al. A novel newborn rat kernicterus model created by injecting a bilirubin solution into the cisterna magna. PLoS One, 2014, 9(5):e96171.
5.	Gao X, Yang X, Zhang B. Neuroprotection of taurine against bilirubin-induced elevation of apoptosis and intracellular free calcium ion in vivo. Toxicol Mech Methods, 2011, 21(5):383-387.
6.	Hachiya Y, Hayashi M. Bilirubin encephalopathy:a study of neuronal subpopulations and neurodegenerative mechanisms in 12 autopsy cases. Brain Dev, 2008, 30(4):269-278.
7.	Silva RF, Rodrigues CM, Brites D. Rat cultured neuronal and glial cells respond differently to toxicity of unconjugated bilirubin. Pediatr Res, 2002, 51(4):535-541.
8.	Hankø E, Hansen TW, Almaas R, et al. Bilirubin induces apoptosis and necrosis in human NT2-N neurons. Pediatr Res, 2005, 57(2):179-184.
9.	Tabarki B, Khalifa M, Yacoub M, et al. Cerebellar symptoms heral-ding bilirubin encephalopathy in Crigler-Najjar syndrome. Pediatr Neurol, 2002, 27(3):234-236.
10.	Furukawa Y. Histological changes in the brain due to experimental obstructive jaundice. Nihon Geka Gakkai Zasshi, 1991, 92(1):37-45.
11.	Chroni E, Patsoukis N, Karageorgos N, et al. Brain oxidative stress induced by obstructive jaundice in rats. J Neuropathol Exp Neurol, 2006, 65(2):193-198.
12.	Lau CG, Zukin RS. NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders. Nat Rev Neurosci, 2007, 8(6):413-426.
13.	Xu B, Xu Z, Deng Y, et al. MK-801 protects against intracellular Ca(2+) overloading and improves N-methyl-D-aspartate receptor expression in cerebral cortex of methylmercury-poisoned rats. J Mol Neurosci, 2013, 49(1):162-171.
14.	Cull-Candy S, Brickley S, Farrant M. NMDA receptor subunits:diversity, development and disease. Curr Opin Neurobiol, 2001, 11 (3):327-335.
15.	Fan MM, Raymond LA. N-methyl-D-aspartate (NMDA) receptor function and excitotoxicity in Huntington, s disease. Prog Neurobiol, 2007, 81(5/6):272-293.
16.	Paoletti P. Molecular basis of NMDA receptor functional diversity. Eur J Neurosci, 2011, 33(8):1351-1365.
17.	Kew JN, Kemp JA. Ionotropic and metabotropic glutamate receptor structure and pharmacology. Psychopharmacology (Berl), 2005, 179(1):4-29.
18.	Hardingham GE, Bading H. The yin and yang of NMDA receptor signalling. Trends Neurosci, 2003, 26(2):81-89.
19.	Massey PV, Johnson BE, Moult PR, et al. Differential roles of NR2A and NR2B-containing NMDA receptors in cortical long-term potentiation and long-term depression. J Neurosci, 2004, 24(36):7821-7828.
20.	Kosenko E, Venediktova N, Kaminsky Y, et al. Sources of oxygen radicals in brain in acute ammonia intoxication in vivo. Brain Res, 2003, 981(1/2):193-200.
21.	Marcaida G, Felipo V, Hermenegildo C, et al. Acute ammonia toxicity is mediated by the NMDA type of glutamate receptors. FEBS Lett, 1992, 296(1):67-68.
22.	Hermenegildo C, Marcaida G, Montoliu C, et al. NMDA receptor antagonists prevent acute ammonia toxicity in mice. Neurochem Res, 1996, 21(10):1237-1244.
23.	Novelli A, Reilly JA, Lysko PG, et al. Glutamate becomes neurotoxic via the N-methyl-D-aspartate receptor when intracellular energy levels are reduced. Brain Res, 1988, 451(1/2):205-212.
24.	Lee JM, Zipfel GJ, Choi DW. The changing landscape of ischaemic brain injury mechanisms. Nature, 1999, 399(6738 Suppl):A7-A14.
25.	Ikonomidou C, Bosch F, Miksa M, et al. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science, 1999, 283(5398):70-74.
26.	Palmer C, Smith MB. Assessing the risk of kernicterus using nuclear magnetic resonance. Clin Perinatol, 1990, 17(2):307-329.
27.	McDonald JW, Shapiro SM, Silverstein FS, et al. Role of glutamate receptor-mediated excitotoxicity in bilirubin-induced brain injury in the Gunn rat model. Exp Neurol, 1998, 150(1):21-29.
28.	Grojean S, Koziel V, Vert P, et al. Bilirubin induces apoptosis via activation of NMDA receptors in developing rat brain neurons. Exp Neurol, 2000, 166(2):334-341.
29.	Wennberg RP, Hance AJ. Experimental bilirubin encephalopathy:importance of total bilirubin, protein binding, and blood-brain barrier. Pediatr Res, 1986, 20(8):789-792.
30.	Sarici SU, Saldir M. Genetic factors in neonatal hyperbilirubinemia and kernicterus. Turk J Pediatr, 2007, 49(3):245-249.
31.	Lee CH, Lü W, Michel JC, et al. NMDA receptor structures reveal subunit arrangement and pore architecture. Nature, 2014, 511(758):191-197.
32.	Wu Q, Zheng R, Srisai D, et al. NR2B subunit of the NMDA gluta-mate receptor regulates appetite in the parabrachial nucleus. Proc Natl Acad Sci U S A, 2013, 110(36):14765-14770.
33.	Mishizen-Eberz AJ, Rissman RA, Carter TL, et al. Biochemical and molecular studies of NMDA receptor subunits NR1/2A/2B in hippocampal subregions throughout progression of Alzheimer's disease pathology. Neurobiol Dis, 2004, 15(1):80-92.
34.	Dunah AW, Wang Y, Yasuda RP, et al. Alterations in subunit expression, composition, and phosphorylation of striatal N-methyl-D-aspartate glutamate receptors in a rat 6-hydroxydopamine model of Parkinson, s disease. Mol Pharmacol, 2000, 57(2):342-352.
35.	Paoletti P, Bellone C, Zhou Q. NMDA receptor subunit diversity:impact on receptor properties, synaptic plasticity and disease. Nat Rev Neurosci, 2013, 14(6):383-400.
36.	Thomas CG, Miller AJ, Westbrook GL. Synaptic and extrasynaptic NMDA receptor NR2 subunits in cultured hippocampal neurons. J Neurophysiol, 2006, 95(3):1727-1734.
37.	Hardingham GE, Bading H. Synaptic versus extrasynaptic NMDA receptor signalling:implications for neurodegenerative disorders. Nat Rev Neurosci, 2010, 11(10):682-696.
38.	Mazumder M K, Borah A. Piroxicam inhibits NMDA receptor-mediated excitotoxicity through allosteric inhibition of the GluN2B subunit:an in silico study elucidating a novel mechanism of action of the drug. Med Hypotheses, 2014, 83(6):740-746.
39.	Liu Y, Wong TP, Aarts M, et al. NMDA receptor subunits have differential roles in mediating excitotoxic neuronal death both in vitro and in vivo. J Neurosci, 2007, 27(11):2846-2857.
40.	Chen M, Lu TJ, Chen XJ, et al. Differential roles of NMDA receptor subtypes in ischemic neuronal cell death and ischemic tolerance. Stroke, 2008, 39(11):3042-3048.
41.	Lu C, Chan SL, Haughey N, et al. Selective and biphasic effect of the membrane lipid peroxidation product 4-hydroxy-2, 3-nonenal on N-methyl-D-aspartate channels. J Neurochem, 2001, 78(3):577-589.
42.	Yang L, Li X B, Yang Q, et al. The neuroprotective effect of praeruptorin C against NMDA-induced apoptosis through down-regulating of GluN2B-containing NMDA receptors. Toxicol In Vitro, 2013, 27(2):908-914.
43.	Papadia S, Hardingham GE. The dichotomy of NMDA receptor signaling. Neuroscientist, 2007, 13(6):572-579.
44.	Lafon-Cazal M, Pietri S, Culcasi M, et al. NMDA-dependent superoxide production and neurotoxicity. Nature, 1993, 364(6437):535-537.
45.	Betzen C, White R, Zehendner CM, et al. Oxidative stress upregu-lates the NMDA receptor on cerebrovascular endothelium. Free Radic Biol Med, 2009, 47(8):1212-1220.
46.	Dawson TM, Dawson VL, Snyder SH. A novel neuronal messenger molecule in brain:the free radical, nitric oxide. Ann Neurol, 1992, 32(3):297-311.
47.	Saraf MK, Prabhakar S, Anand A. Bacopa monniera alleviates N (omega)-nitro-L-arginine arginine-induced but not MK-801-induced amnesia:a mouse Morris watermaze study. Neuroscience, 2009, 160(1):149-155.
48.	Kosenko E, Kaminski Y, Lopata O, et al. Blocking NMDA receptors prevents the oxidative stress induced by acute ammonia intoxica-tion. Free Radic Biol Med, 1999, 26(11/12):1369-1374.
49.	Gáspárová-Kvaltínová Z, Stolc S. Effect of antioxidants and NMDA antagonists on the density of NMDA binding sites in rat hippoca-mpal slices exposed to hypoxia/reoxygenation. Methods Find Exp Clin Pharmacol, 2003, 25(1):17-25.
50.	Mizoguchi H, Komatsu T, Iwata Y, et al. Partial involvement of NMDA receptors and glial cells in the nociceptive behaviors induced by intrathecally administered histamine. Neurosci Lett, 2011, 495(2):83-87.
51.	Furuya T, Pan Z, Kashiwagi K. Role of retinal glial cell glutamate transporters in retinal ganglion cell survival following stimulation of NMDA receptor. Curr Eye Res, 2012, 37(3):170-178.
52.	Jun SB, Smith KL, Shain W, et al. Optical monitoring of neural networks evoked by focal electrical stimulation on microelectrode arrays using FM dyes. Med Biol Eng Comput, 2010, 48(9):933-940.
53.	Hires SA, Zhu Y, Tsien RY. Optical measurement of synaptic glutamate spillover and reuptake by linker optimized glutamate-sensitive fluorescent reporters. Proc Natl Acad Sci U S A, 2008, 105(11):4411-4416.
54.	Romón T, Planas AM, Adell A. Blockade of MK-801-induced heat shock protein 72/73 in rat brain by antipsychotic and monoaminergic agents targeting D2, 5-HT1A, 5-HT2A andα1-adrenergic receptors. CNS Neurol Disord Drug Targets, 2014, 13(1):104-111.
55.	Hoffman DJ, Zanelli SA, Kubin J, et al. The in vivo effect of bilirubin on the N-methyl-D-aspartate receptor/ion channel complex in the brains of newborn piglets. Pediatr Res, 1996, 40(6):804-808.
56.	Jara-Prado A, Ortega-Vazquez A, Martinez-Ruano L, et al. Homocy-steine-induced brain lipid peroxidation:effects of NMDA receptor blockade, antioxidant treatment, and nitric oxide synthase inhibi-tion. Neurotox Res, 2003, 5(4):237-243.
57.	崔红梅, 常秀丽, 徐甫, 等. MK801抑制乐果诱导的大鼠皮层神经元凋亡的作用研究.卫生研究, 2011, 40(5):568-572.
58.	Liang CL, Yang LC, Lu K, et al. Neuroprotective synergy of N-methyl-D-aspartate receptor antagonist (Mk801) and protein synthesis inhibitor (cycloheximide) on spinal cord ischemia-reperfusion injury in rats. J Neurotrauma, 2003, 20(2):195-206.
59.	Fletcher PJ, Rizos Z, Noble K, et al. Impulsive action induced by amphetamine, cocaine and Mk801 is reduced by 5-HT(2C) receptor stimulation and 5-HT(2A) receptor blockade. Neuropharmacology, 2011, 61(3):468-477.

1. Qin LX, Tang ZY. Hepatocellular carcinoma with obstructive jaun-dice:diagnosis, treatment and prognosis. World J Gastroenterol, 2003, 9(3):385-391.
2. Iskander I, Gamaleldin R, El Houchi S, et al. Serum bilirubin and bilirubin/albumin ratio as predictors of bilirubin encephalopathy. Pediatrics, 2014, 134(5):e1330-e1339.
3. Diamond I, Schmid R. The pathogenesis of bilirubin encephalopathy:experimental models in newborn and adult animals. Trans Am Neurol Assoc, 1965, 90:38-41.
4. Song S, Hu Y, Gu X, et al. A novel newborn rat kernicterus model created by injecting a bilirubin solution into the cisterna magna. PLoS One, 2014, 9(5):e96171.
5. Gao X, Yang X, Zhang B. Neuroprotection of taurine against bilirubin-induced elevation of apoptosis and intracellular free calcium ion in vivo. Toxicol Mech Methods, 2011, 21(5):383-387.
6. Hachiya Y, Hayashi M. Bilirubin encephalopathy:a study of neuronal subpopulations and neurodegenerative mechanisms in 12 autopsy cases. Brain Dev, 2008, 30(4):269-278.
7. Silva RF, Rodrigues CM, Brites D. Rat cultured neuronal and glial cells respond differently to toxicity of unconjugated bilirubin. Pediatr Res, 2002, 51(4):535-541.
8. Hankø E, Hansen TW, Almaas R, et al. Bilirubin induces apoptosis and necrosis in human NT2-N neurons. Pediatr Res, 2005, 57(2):179-184.
9. Tabarki B, Khalifa M, Yacoub M, et al. Cerebellar symptoms heral-ding bilirubin encephalopathy in Crigler-Najjar syndrome. Pediatr Neurol, 2002, 27(3):234-236.
10. Furukawa Y. Histological changes in the brain due to experimental obstructive jaundice. Nihon Geka Gakkai Zasshi, 1991, 92(1):37-45.
11. Chroni E, Patsoukis N, Karageorgos N, et al. Brain oxidative stress induced by obstructive jaundice in rats. J Neuropathol Exp Neurol, 2006, 65(2):193-198.
12. Lau CG, Zukin RS. NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders. Nat Rev Neurosci, 2007, 8(6):413-426.
13. Xu B, Xu Z, Deng Y, et al. MK-801 protects against intracellular Ca(2+) overloading and improves N-methyl-D-aspartate receptor expression in cerebral cortex of methylmercury-poisoned rats. J Mol Neurosci, 2013, 49(1):162-171.
14. Cull-Candy S, Brickley S, Farrant M. NMDA receptor subunits:diversity, development and disease. Curr Opin Neurobiol, 2001, 11 (3):327-335.
15. Fan MM, Raymond LA. N-methyl-D-aspartate (NMDA) receptor function and excitotoxicity in Huntington, s disease. Prog Neurobiol, 2007, 81(5/6):272-293.
16. Paoletti P. Molecular basis of NMDA receptor functional diversity. Eur J Neurosci, 2011, 33(8):1351-1365.
17. Kew JN, Kemp JA. Ionotropic and metabotropic glutamate receptor structure and pharmacology. Psychopharmacology (Berl), 2005, 179(1):4-29.
18. Hardingham GE, Bading H. The yin and yang of NMDA receptor signalling. Trends Neurosci, 2003, 26(2):81-89.
19. Massey PV, Johnson BE, Moult PR, et al. Differential roles of NR2A and NR2B-containing NMDA receptors in cortical long-term potentiation and long-term depression. J Neurosci, 2004, 24(36):7821-7828.
20. Kosenko E, Venediktova N, Kaminsky Y, et al. Sources of oxygen radicals in brain in acute ammonia intoxication in vivo. Brain Res, 2003, 981(1/2):193-200.
21. Marcaida G, Felipo V, Hermenegildo C, et al. Acute ammonia toxicity is mediated by the NMDA type of glutamate receptors. FEBS Lett, 1992, 296(1):67-68.
22. Hermenegildo C, Marcaida G, Montoliu C, et al. NMDA receptor antagonists prevent acute ammonia toxicity in mice. Neurochem Res, 1996, 21(10):1237-1244.
23. Novelli A, Reilly JA, Lysko PG, et al. Glutamate becomes neurotoxic via the N-methyl-D-aspartate receptor when intracellular energy levels are reduced. Brain Res, 1988, 451(1/2):205-212.
24. Lee JM, Zipfel GJ, Choi DW. The changing landscape of ischaemic brain injury mechanisms. Nature, 1999, 399(6738 Suppl):A7-A14.
25. Ikonomidou C, Bosch F, Miksa M, et al. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science, 1999, 283(5398):70-74.
26. Palmer C, Smith MB. Assessing the risk of kernicterus using nuclear magnetic resonance. Clin Perinatol, 1990, 17(2):307-329.
27. McDonald JW, Shapiro SM, Silverstein FS, et al. Role of glutamate receptor-mediated excitotoxicity in bilirubin-induced brain injury in the Gunn rat model. Exp Neurol, 1998, 150(1):21-29.
28. Grojean S, Koziel V, Vert P, et al. Bilirubin induces apoptosis via activation of NMDA receptors in developing rat brain neurons. Exp Neurol, 2000, 166(2):334-341.
29. Wennberg RP, Hance AJ. Experimental bilirubin encephalopathy:importance of total bilirubin, protein binding, and blood-brain barrier. Pediatr Res, 1986, 20(8):789-792.
30. Sarici SU, Saldir M. Genetic factors in neonatal hyperbilirubinemia and kernicterus. Turk J Pediatr, 2007, 49(3):245-249.
31. Lee CH, Lü W, Michel JC, et al. NMDA receptor structures reveal subunit arrangement and pore architecture. Nature, 2014, 511(758):191-197.
32. Wu Q, Zheng R, Srisai D, et al. NR2B subunit of the NMDA gluta-mate receptor regulates appetite in the parabrachial nucleus. Proc Natl Acad Sci U S A, 2013, 110(36):14765-14770.
33. Mishizen-Eberz AJ, Rissman RA, Carter TL, et al. Biochemical and molecular studies of NMDA receptor subunits NR1/2A/2B in hippocampal subregions throughout progression of Alzheimer's disease pathology. Neurobiol Dis, 2004, 15(1):80-92.
34. Dunah AW, Wang Y, Yasuda RP, et al. Alterations in subunit expression, composition, and phosphorylation of striatal N-methyl-D-aspartate glutamate receptors in a rat 6-hydroxydopamine model of Parkinson, s disease. Mol Pharmacol, 2000, 57(2):342-352.
35. Paoletti P, Bellone C, Zhou Q. NMDA receptor subunit diversity:impact on receptor properties, synaptic plasticity and disease. Nat Rev Neurosci, 2013, 14(6):383-400.
36. Thomas CG, Miller AJ, Westbrook GL. Synaptic and extrasynaptic NMDA receptor NR2 subunits in cultured hippocampal neurons. J Neurophysiol, 2006, 95(3):1727-1734.
37. Hardingham GE, Bading H. Synaptic versus extrasynaptic NMDA receptor signalling:implications for neurodegenerative disorders. Nat Rev Neurosci, 2010, 11(10):682-696.
38. Mazumder M K, Borah A. Piroxicam inhibits NMDA receptor-mediated excitotoxicity through allosteric inhibition of the GluN2B subunit:an in silico study elucidating a novel mechanism of action of the drug. Med Hypotheses, 2014, 83(6):740-746.
39. Liu Y, Wong TP, Aarts M, et al. NMDA receptor subunits have differential roles in mediating excitotoxic neuronal death both in vitro and in vivo. J Neurosci, 2007, 27(11):2846-2857.
40. Chen M, Lu TJ, Chen XJ, et al. Differential roles of NMDA receptor subtypes in ischemic neuronal cell death and ischemic tolerance. Stroke, 2008, 39(11):3042-3048.
41. Lu C, Chan SL, Haughey N, et al. Selective and biphasic effect of the membrane lipid peroxidation product 4-hydroxy-2, 3-nonenal on N-methyl-D-aspartate channels. J Neurochem, 2001, 78(3):577-589.
42. Yang L, Li X B, Yang Q, et al. The neuroprotective effect of praeruptorin C against NMDA-induced apoptosis through down-regulating of GluN2B-containing NMDA receptors. Toxicol In Vitro, 2013, 27(2):908-914.
43. Papadia S, Hardingham GE. The dichotomy of NMDA receptor signaling. Neuroscientist, 2007, 13(6):572-579.
44. Lafon-Cazal M, Pietri S, Culcasi M, et al. NMDA-dependent superoxide production and neurotoxicity. Nature, 1993, 364(6437):535-537.
45. Betzen C, White R, Zehendner CM, et al. Oxidative stress upregu-lates the NMDA receptor on cerebrovascular endothelium. Free Radic Biol Med, 2009, 47(8):1212-1220.
46. Dawson TM, Dawson VL, Snyder SH. A novel neuronal messenger molecule in brain:the free radical, nitric oxide. Ann Neurol, 1992, 32(3):297-311.
47. Saraf MK, Prabhakar S, Anand A. Bacopa monniera alleviates N (omega)-nitro-L-arginine arginine-induced but not MK-801-induced amnesia:a mouse Morris watermaze study. Neuroscience, 2009, 160(1):149-155.
48. Kosenko E, Kaminski Y, Lopata O, et al. Blocking NMDA receptors prevents the oxidative stress induced by acute ammonia intoxica-tion. Free Radic Biol Med, 1999, 26(11/12):1369-1374.
49. Gáspárová-Kvaltínová Z, Stolc S. Effect of antioxidants and NMDA antagonists on the density of NMDA binding sites in rat hippoca-mpal slices exposed to hypoxia/reoxygenation. Methods Find Exp Clin Pharmacol, 2003, 25(1):17-25.
50. Mizoguchi H, Komatsu T, Iwata Y, et al. Partial involvement of NMDA receptors and glial cells in the nociceptive behaviors induced by intrathecally administered histamine. Neurosci Lett, 2011, 495(2):83-87.
51. Furuya T, Pan Z, Kashiwagi K. Role of retinal glial cell glutamate transporters in retinal ganglion cell survival following stimulation of NMDA receptor. Curr Eye Res, 2012, 37(3):170-178.
52. Jun SB, Smith KL, Shain W, et al. Optical monitoring of neural networks evoked by focal electrical stimulation on microelectrode arrays using FM dyes. Med Biol Eng Comput, 2010, 48(9):933-940.
53. Hires SA, Zhu Y, Tsien RY. Optical measurement of synaptic glutamate spillover and reuptake by linker optimized glutamate-sensitive fluorescent reporters. Proc Natl Acad Sci U S A, 2008, 105(11):4411-4416.
54. Romón T, Planas AM, Adell A. Blockade of MK-801-induced heat shock protein 72/73 in rat brain by antipsychotic and monoaminergic agents targeting D2, 5-HT1A, 5-HT2A andα1-adrenergic receptors. CNS Neurol Disord Drug Targets, 2014, 13(1):104-111.
55. Hoffman DJ, Zanelli SA, Kubin J, et al. The in vivo effect of bilirubin on the N-methyl-D-aspartate receptor/ion channel complex in the brains of newborn piglets. Pediatr Res, 1996, 40(6):804-808.
56. Jara-Prado A, Ortega-Vazquez A, Martinez-Ruano L, et al. Homocy-steine-induced brain lipid peroxidation:effects of NMDA receptor blockade, antioxidant treatment, and nitric oxide synthase inhibi-tion. Neurotox Res, 2003, 5(4):237-243.
57. 崔红梅, 常秀丽, 徐甫, 等. MK801抑制乐果诱导的大鼠皮层神经元凋亡的作用研究.卫生研究, 2011, 40(5):568-572.
58. Liang CL, Yang LC, Lu K, et al. Neuroprotective synergy of N-methyl-D-aspartate receptor antagonist (Mk801) and protein synthesis inhibitor (cycloheximide) on spinal cord ischemia-reperfusion injury in rats. J Neurotrauma, 2003, 20(2):195-206.
59. Fletcher PJ, Rizos Z, Noble K, et al. Impulsive action induced by amphetamine, cocaine and Mk801 is reduced by 5-HT(2C) receptor stimulation and 5-HT(2A) receptor blockade. Neuropharmacology, 2011, 61(3):468-477.

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Role of NMDA Receptor in Central Nervous System Injury of Obstructive Jaundice

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