Glutamate transporters in brain ischemia: to modulate or not?

Acta Pharmacologica Sinica

Volumn 35, Issue 4, 2014, Pages 444-462

  Krzyzanowska, Weronika ^a   Pomierny, Bartosz ^a   Filip, Magłorzata ^a   Pera, Joanna ^a  

^a JAGIELLONIAN UNIVERSITY MEDICAL COLLEGE   (Poland)

Author keywords

Brain ischemia; Ceftriaxone; Cystine glutamate antiporter; Excitatory amino acid transporter; Glutamate; Ischemic preconditioning; Vesicular glutamate transporter

Indexed keywords

ACETYLCYSTEINE; AMITRIPTYLINE; ANTIPORTER; BETA LACTAM ANTIBIOTIC; CEFTRIAXONE; CYSTINE; EXCITATORY AMINO ACID TRANSPORTER 1; EXCITATORY AMINO ACID TRANSPORTER 2; GLUTAMATE TRANSPORTER; GLUTAMIC ACID; RILUZOLE; VESICULAR GLUTAMATE TRANSPORTER 1; VESICULAR GLUTAMATE TRANSPORTER 2; VESICULAR GLUTAMATE TRANSPORTER 3; AMINO ACID TRANSPORTER; NEUROPROTECTIVE AGENT; VESICULAR GLUTAMATE TRANSPORTER;

AMINO ACID METABOLISM; AMINO ACID TRANSPORT; BRAIN INFARCTION; BRAIN ISCHEMIA; CENTRAL NERVOUS SYSTEM; DRUG MECHANISM; HUMAN; ISCHEMIC PRECONDITIONING; MIDDLE CEREBRAL ARTERY OCCLUSION; NEUROMODULATION; NEUROPROTECTION; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; REGULATORY MECHANISM; REVIEW; ANIMAL; BRAIN; DRUG EFFECTS; METABOLISM; PATHOLOGY; SYNAPTIC TRANSMISSION; TREATMENT OUTCOME;

AMINO ACID TRANSPORT SYSTEMS, ACIDIC; ANIMALS; BRAIN; BRAIN ISCHEMIA; GLUTAMATE PLASMA MEMBRANE TRANSPORT PROTEINS; GLUTAMIC ACID; HUMANS; ISCHEMIC PRECONDITIONING; NEUROPROTECTIVE AGENTS; SYNAPTIC TRANSMISSION; TREATMENT OUTCOME; VESICULAR GLUTAMATE TRANSPORT PROTEINS;

EID: 84898759552     PISSN: 16714083     EISSN: 17457254     Source Type: Journal    
DOI: 10.1038/aps.2014.1     Document Type: Review

References (233)

1. Danbolt NC. Glutamate uptake. Prog Neurobiol 2001; 65: 1-105
2. Choi DW. Cerebral hypoxia: Some new approaches and unanswered questions. J Neurosci 1990; 10: 2493-501
3. Malarkey EB, Parpura V. Mechanisms of glutamate release from astrocytes. Neurochem Int 2008; 52: 142-54
4. Bezzi P, Gundersen V, Galbete JL, Seifert G, Steinhauser C, Pilati E, et al. Astrocytes contain a vesicular compartment that is competent for regulated exocytosis of glutamate. Nat Neurosci 2004; 7: 613-20
5. Ankarcrona M, Dypbukt JM, Bonfoco E, Zhivotovsky B, Orrenius S, Lipton SA, et al. Glutamate-induced neuronal death: A succession of necrosis or apoptosis depending on mitochondrial function. Neuron 1995; 15: 961-73
6. Zou J, Wang YX, Dou FF, Lu HZ, Ma ZW, Lu PH, et al. Glutamine synthetase down-regulation reduces astrocyte protection against glutamate excitotoxicity to neurons. Neurochem Int 2010; 56: 577-84
7. Pellerin L, Magistretti PJ. Glutamate uptake into astrocytes stimulates aerobic glycolysis: A mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci U S A 1994; 91: 10625-9
8. Pellerin L, Magistretti PJ. Neuroenergetics: Calling upon astrocytes to satisfy hungry neurons. Neuroscientist 2004; 10: 53-62
9. Martin DL. Mechanisms controlling ced synthesis and degradation in the brain. In: Martin DL, editor. GABA in the nervous system. Philadelphia: Lippincott Williams & Wilkins; 2000. p 25-41
10. McBean GJ. Cerebral cystine uptake: A tale of two transporters. Trends Pharmacol Sci 2002; 23: 299-302
11. Westbrook GL. Glutamate receptors and excitotoxicity. Res Publ Assoc Res Nerv Ment Dis 1993; 71: 35-50
12. Zheng K, Scimemi A, Rusakov DA. Receptor actions of synaptically released glutamate: The role of transporters on the scale from nanometers to microns. Biophys J 2008; 95: 4584-96
13. Niciu MJ, Kelmendi B, Sanacora G. Overview of glutamatergic neurotransmission in the nervous system. Pharmacol Biochem Behav 2012; 100: 656-64
14. Beretta S, Begni B, Ferrarese C. Pharmacological manipulation of glutamate transport. Drug News Perspect 2003; 16: 435-45
15. Zerangue N, Kavanaugh MP. Flux coupling in a neuronal glutamate transporter. Nature 1996; 383: 634-7
16. Fremeau RT Jr, Voglmaier S, Seal RP, Edwards RH. VGLUTs define subsets of excitatory neurons and suggest novel roles for glutamate. Trends Neurosci 2004; 27: 98-103
17. Erecinska M, Silver IA. Metabolism and role of glutamate in mammalian brain. Prog Neurobiol 1990; 35: 245-96
18. Birnbaumer L, Campbell KP, Catterall WA, Harpold MM, Hofmann F, Horne WA, et al. The naming of voltage-gated calcium channels. Neuron 1994; 13: 505-6
19. Levy LM, Warr O, Attwell D. Stoichiometry of the glial glutamate transporter GLT-1 expressed inducibly in a Chinese hamster ovary cell line selected for low endogenous Na+-dependent glutamate uptake. J Neurosci 1998; 18: 9620-8
20. Dingledine R, Borges K, Bowie D, Traynelis SF. The glutamate receptor ion channels. Pharmacol Rev 1999; 51: 7-61
21. Papadia S, Soriano FX, Leveille F, Martel M, Dakin KA, Hansen HH, et al. Synaptic NMDA receptor activity boosts intrinsic antioxidant defenses. Nat Neurosci 2008; 11: 476-87
22. Hardingham GE, Arnold FJL, Bading H. A calcium microdomain near NMDA receptors: On switch for ERK-dependent synapse-To-nucleus communication. Nat Neurosci 2001; 4: 565-6
23. Hardingham GE, Arnold FJL, Bading H. Nuclear calcium signaling controls CREB-mediated gene expression triggered by synaptic activity. Nat Neurosci 2001; 4: 261-7
24. Papouin T, Ladepeche L, Ruel J, Sacchi S, Labasque M, Hanini M, et al. Synaptic and extrasynaptic NMDA receptors are gated by different endogenous coagonists. Cell 2012; 150: 633-46
25. Olney JW. Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate. Science 1969; 164: 719-21
26. Cano-Abad MF, Villarroya M, Garcia AG, Gabilan NH, Lopez MG. Calcium entry through L-Type calcium channels causes mitochondrial disruption and chromaffin cell death. J Biol Chem 2001; 276: 39695-704
27. Kostandy BB. The role of glutamate in neuronal ischemic injury: The role of spark in fire. Neurol Sci 2012; 33: 223-37
28. Celsi F, Pizzo P, Brini M, Leo S, Fotino C, Pinton P, et al. Mitochondria, calcium and cell death: A deadly triad in neurodegeneration. Biochim Biophys Acta Bioenerg 2009; 1787: 335-44
29. Conn PJ, Pin JP. Pharmacology and functions of metabotropic glutamate receptors. Annu Rev Pharmacol Toxicol 1997; 37: 205-37
30. Ferraguti F, Shigemoto R. Metabotropic glutamate receptors. Cell Tissue Res 2006; 326: 483-504
31. Pilc A, Chaki S, Nowak G, Witkin JM. Mood disorders: Regulation by metabotropic glutamate receptors. Biochem Pharmacol 2008; 75: 997-1006
32. Francesconi A, Duvoisin RM. Opposing effects of protein kinase C and protein kinase A on metabotropic glutamate receptor signaling: Selective desensitization of the inositol trisphosphate/Ca2+ pathway by phosphorylation of the receptor-G protein-coupling domain. Proc Natl Acad Sci U S A 2000; 97: 6185-90
33. Sheng M. Molecular organization of the postsynaptic specialization. Proc Natl Acad Sci U S A 2001; 98: 7058-61
34. Herrero I, Miras-Portugal MT, Sanchez-Prieto J. Functional switch from facilitation to inhibition in the control of glutamate release by metabotropic glutamate receptors. J Biol Chem 1998; 273: 1951-8
35. Bruno V, Battaglia G, Copani A, Cespedes VM, Galindo MF, Cena V, et al. An activity-dependent switch from facilitation to inhibition in the control of excitotoxicity by group I metabotropic glutamate receptors. Eur J Neurosci 2001; 13: 1469-78
36. Pinheiro PS, Mulle C. Presynaptic glutamate receptors: Physiological functions and mechanisms of action. Nat Rev Neurosci 2008; 9: 423-36
37. Anwyl R. Metabotropic glutamate receptors: Electrophysiological properties and role in plasticity. Brain Res Brain Res Rev 1999; 29: 83-120
38. Wieronska JM, Pilc A. Metabotropic glutamate receptors in the tripartite synapse as a target for new psychotropic drugs. Neurochem Int 2009; 55: 85-97
39. Tamaru Y, Nomura S, Mizuno N, Shigemoto R. Distribution of metabotropic glutamate receptor mGluR3 in the mouse CNS: Differential location relative to pre-And postsynaptic sites. Neuroscience 2001; 106: 481-503
40. van den Pol AN, Romano C, Ghosh P. Metabotropic glutamate receptor mGluR5 subcellular distribution and developmental expression in hypothalamus. J Comp Neurol 1995; 362: 134-50
41. Kim K, Lee SG, Kegelman TP, Su ZZ, Das SK, Dash R, et al. Role of excitatory amino acid transporter-2 (EAAT2) and glutamate in neurodegeneration: Opportunities for developing novel therapeutics. J Cell Physiol 2011; 226: 2484-93
42. Burdo J, Dargusch R, Schubert D. Distribution of the cystine/glutamate antiporter system xc-in the brain, kidney, and duodenum. J Histochem Cytochem 2006; 54: 549-57
43. Liguz-Lecznar M, Skangiel-Kramska J. Vesicular glutamate transporters (VGLUTs): The three musketeers of glutamatergic system. Acta Neurobiol Exp (Wars) 2007; 67: 207-18
44. Ozawa T, Nakagawa T, Shige K, Minami M, Satoh M. Changes in the expression of glial glutamate transporters in the rat brain accompanied with morphine dependence and naloxone-precipitated withdrawal. Brain Res 2001; 905: 254-8
45. Storck T, Schulte S, Hofmann K, Stoffel W. Structure, expression, and functional analysis of a Na+-dependent glutamate/aspartate transporter from rat brain. Proc Natl Acad Sci U S A 1992; 89: 10955-9
46. Harada T, Harada C, Watanabe M, Inoue Y, Sakagawa T, Nakayama N, et al. Functions of the two glutamate transporters GLAST and GLT-1 in the retina. Proc Natl Acad Sci U S A 1998; 95: 4663-6
47. Derouiche A, Rauen T. Coincidence of L-glutamate/L-Aspartate transporter (GLAST) and glutamine synthetase (GS) immunoreactions in retinal glia: Evidence for coupling of GLAST and GS in transmitter clearance. J Neurosci Res 1995; 42: 131-43
48. Otori Y, Shimada S, Tanaka K, Ishimoto I, Tano Y, Tohyama M. Marked increase in glutamate-Aspartate transporter (GLAST/GluT-1) mRNA following transient retinal ischemia. Brain Res Mol Brain Res 1994; 27: 310-4
49. Li HS, Niedzielski AS, Beisel KW, Hiel H, Wenthold RJ, Morley BJ. Identification of a glutamate/aspartate transporter in the rat cochlea. Hear Res 1994; 78: 235-42
50. Kondo K, Hashimoto H, Kitanaka J, Sawada M, Suzumura A, Marunouchi T, et al. Expression of glutamate transporters in cultured glial cells. Neurosci Lett 1995; 188: 140-2
51. Gegelashvili G, Civenni G, Racagni G, Danbolt NC, Schousboe I, Schousboe A. Glutamate receptor agonists up-regulate glutamate transporter GLAST in astrocytes. Neuroreport 1996; 8: 261-5
52. Ramachandran B, Houben K, Rozenberg YY, Haigh JR, Varpetian A, Howard BD. Differential expression of transporters for norepinephrine and glutamate in wild type, variant, and WNT1-expressing PC12 cells. J Biol Chem 1993; 268: 23891-7
53. Perego C, Vanoni C, Bossi M, Massari S, Basudev H, Longhi R, et al. The GLT-1 and GLAST glutamate transporters are expressed on morphologically distinct astrocytes and regulated by neuronal activity in primary hippocampal cocultures. J Neurochem 2000; 75: 1076-84
54. Ward MM, Jobling AI, Puthussery T, Foster LE, Fletcher EL. Localization and expression of the glutamate transporter, excitatory amino acid transporter 4, within astrocytes of the rat retina. Cell Tissue Res 2004; 315: 305-10
55. Kanai Y, Hediger MA. The glutamate/neutral amino acid transporter family SLC1: Molecular, physiological and pharmacological aspects. Pflugers Arch 2004; 447: 469-79
56. Sheldon AL, Robinson MB. The role of glutamate transporters in neurodegenerative diseases and potential opportunities for intervention. Neurochem Int 2007; 51: 333-55
57. Maragakis NJ, Dietrich J, Wong V, Xue H, Mayer-Proschel M, Rao MS, et al. Glutamate transporter expression and function in human glial progenitors. Glia 2004; 45: 133-43
58. Mennerick S, Dhond RP, Benz A, Xu W, Rothstein JD, Danbolt NC, et al. Neuronal expression of the glutamate transporter GLT-1 in hippocampal microcultures. J Neurosci 1998; 18: 4490-9
59. Liang J, Takeuchi H, Doi Y, Kawanokuchi J, Sonobe Y, Jin S, et al. Excitatory amino acid transporter expression by astrocytes is neuroprotective against microglial excitotoxicity. Brain Res 2008; 1210: 11-9
60. Rothstein JD, Martin L, Levey AI, Dykes-Hoberg M, Jin L, Wu D, et al. Localization of neuronal and glial glutamate transporters. Neuron 1994; 13: 713-25
61. Gottlieb M, Domercq M, Matute C. Altered expression of the glutamate transporter EAAC1 in neurons and immature oligodendrocytes after transient forebrain ischemia. J Cereb Blood Flow Metab 2000; 20: 678-87
62. Dehnes Y, Chaudhry FA, Ullensvang K, Lehre KP, Storm-Mathisen J, Danbolt NC. The glutamate transporter EAAT4 in rat cerebellar Purkinje cells: A glutamate-gated chloride channel concentrated near the synapse in parts of the dendritic membrane facing astroglia. J Neurosci 1998; 18: 3606-19
63. Massie A, Cnops L, Smolders I, McCullumsmith R, Kooijman R, Kwak S, et al. High-Affinity Na+/K+-dependent glutamate transporter EAAT4 is expressed throughout the rat fore-And midbrain. J Comp Neurol 2008; 511: 155-72
64. Bar-Peled O, Ben-Hur H, Biegon A, Groner Y, Dewhurst S, Furuta A, et al. Distribution of glutamate transporter subtypes during human brain development. J Neurochem 1997; 69: 2571-80
65. Hu WH, Walters WM, Xia XM, Karmally SA, Bethea Jr. Neuronal glutamate transporter EAAT4 is expressed in astrocytes. Glia 2003; 44: 13-25
66. Schlag BD, Vondrasek JR, Munir M, Kalandadze A, Zelenaia OA, Rothstein JD, et al. Regulation of the glial Na+-dependent glutamate transporters by cyclic AMP analogs and neurons. Mol Pharmacol 1998; 53: 355-69
67. Arriza JL, Eliasof S, Kavanaugh MP, Amara SG. Excitatory amino acid transporter 5, a retinal glutamate transporter coupled to a chloride conductance. Proc Natl Acad Sci U S A 1997; 94: 4155-60
68. Ishige K, Chen Q, Sagara Y, Schubert D. The activation of dopamine D4 receptors inhibits oxidative stress-induced nerve cell death. J Neurosci 2001; 21: 6069-76
69. Sato H, Tamba M, Okuno S, Sato K, Keino-Masu K, Masu M, et al. Distribution of cystine/glutamate exchange transporter, system x(c)-, in the mouse brain. J Neurosci 2002; 22: 8028-33
70. Sasaki H, Sato H, Kuriyama-Matsumura K, Sato K, Maebara K, Wang H, et al. Electrophile response element-mediated induction of the cystine/glutamate exchange transporter gene expression. J Biol Chem 2002; 277: 44765-71
71. Allen JW, Shanker G, Aschner M. Methylmercury inhibits the in vitro uptake of the glutathione precursor, cystine, in astrocytes, but not in neurons. Brain Res 2001; 894: 131-40
72. Piani D, Fontana A. Involvement of the cystine transport system xc-in the macrophage-induced glutamate-dependent cytotoxicity to neurons. J Immunol 1994; 152: 3578-85
73. Kato S, Ishita S, Sugawara K, Mawatari K. Cystine/glutamate antiporter expression in retinal Muller glial cells: Implications for DL-Alpha-Aminoadipate toxicity. Neuroscience 1993; 57: 473-82
74. Murphy TH, Schnaar RL, Coyle JT. Immature cortical neurons are uniquely sensitive to glutamate toxicity by inhibition of cystine uptake. FASEB J 1990; 4: 1624-33
75. Ye ZC, Rothstein JD, Sontheimer H. Compromised glutamate transport in human glioma cells: Reduction-mislocalization of sodium-dependent glutamate transporters and enhanced activity of cystine-glutamate exchange. J Neurosci 1999; 19: 10767-77
76. Hackett TA, Takahata T, Balaram P. VGLUT1 and VGLUT2 mRNA expression in the primate auditory pathway. Hear Res 2011; 274: 129-41
77. Jelks KB, Wylie R, Floyd CL, McAllister AK, Wise P. Estradiol targets synaptic proteins to induce glutamatergic synapse formation in cultured hippocampal neurons: Critical role of estrogen receptor-Alpha. J Neurosci 2007; 27: 6903-13
78. Bjorklund U, Persson M, Ronnback L, Hansson E. Primary cultures from cerebral cortex and hippocampus enriched in glutamatergic and GABAergic neurons. Neurochem Res 2010; 35: 1733-42
79. Nunzi MG, Russo M, Mugnaini E. Vesicular glutamate transporters VGLUT1 and VGLUT2 define two subsets of unipolar brush cells in organotypic cultures of mouse vestibulocerebellum. Neuroscience 2003; 122: 359-71
80. Rothstein JD, Dykes-Hoberg M, Pardo CA, Bristol LA, Jin L, Kuncl RW, et al. Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 1996; 16: 675-86
81. Rauen T, Rothstein JD, Wassle H. Differential expression of three glu¬tamate transporter subtypes in the rat retina. Cell Tissue Res 1996; 286: 325-36
82. Lee SA, Choi JG, Zuo Z. Volatile anesthetics attenuate oxidative stress-reduced activity of glutamate transporter type 3. Anesth Analg 2009; 109: 1506-10
83. Moechars D, Weston MC, Leo S, Callaerts-Vegh Z, Goris I, Daneels G, et al. Vesicular glutamate transporter VGLUT2 expression levels control quantal size and neuropathic pain. J Neurosci 2006; 26: 12055-66
84. Aoyama K, Suh SW, Hamby AM, Liu J, Chan WY, Chen Y, et al. Neuro¬nal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse. Nat Neurosci 2006; 9: 119-26
85. Fairman WA, Vandenberg RJ, Arriza JL, Kavanaugh MP, Amara SG. An excitatory amino-Acid transporter with properties of a ligand-gated chloride channel. Nature 1995; 375: 599-603
86. Fremeau RT Jr, Kam K, Qureshi T, Johnson J, Copenhagen DR, Storm-Mathisen J, et al. Vesicular glutamate transporters 1 and 2 target to functionally distinct synaptic release sites. Science 2004; 304: 1815-9
87. Wojcik SM, Rhee JS, Herzog E, Sigler A, Jahn R, Takamori S, et al. An essential role for vesicular glutamate transporter 1 (VGLUT1) in postnatal development and control of quantal size. Proc Natl Acad Sci U S A 2004; 101: 7158-63
88. Tordera RM, Totterdell S, Wojcik SM, Brose N, Elizalde N, Lasheras B, et al. Enhanced anxiety, depressive-like behaviour and impaired recognition memory in mice with reduced expression of the vesicular glutamate transporter 1 (VGLUT1). Eur J Neurosci 2007; 25: 281-90
89. Miyazaki T, Fukaya M, Shimizu H, Watanabe M. Subtype switching of vesicular glutamate transporters at parallel fibre-Purkinje cell synapses in developing mouse cerebellum. Eur J Neurosci 2003; 17: 2563-72
90. Seal RP, Akil O, Yi E, Weber CM, Grant L, Yoo J, et al. Sensorineural deafness and seizures in mice lacking vesicular glutamate transporter 3. Neuron 2008; 57: 263-75
91. Seal RP, Wang X, Guan Y, Raja SN, Woodbury CJ, Basbaum AI, et al. Injury-induced mechanical hypersensitivity requires C-low threshold mechanoreceptors. Nature 2009; 462: 651-5
92. Omote H, Miyaji T, Juge N, Moriyama Y. Vesicular neurotransmitter transporter: Bioenergetics and regulation of glutamate transport. Biochemistry 2011; 50: 5558-65
93. Bannai S. Exchange of cystine and glutamate across plasma mem¬brane of human fibroblasts. J Biol Chem 1986; 261: 2256-63
94. Cho Y, Bannai S. Uptake of glutamate and cysteine in C-6 glioma cel¬ls and in cultured astrocytes. J Neurochem 1990; 55: 2091-7
95. Dringen R, Hirrlinger J. Glutathione pathways in the brain. Biol Chem 2003; 384: 505-16
96. Tan S, Schubert D, Maher P. Oxytosis: A novel form of programmed cell death. Curr Top Med Chem 2001; 1: 497-506
97. Grewer C, Gameiro A, Zhang Z, Tao Z, Braams S, Rauen T. Gluta¬mate forward and reverse transport: From molecular mechanism to transporter-mediated release after ischemia. IUBMB Life 2008; 60: 609-19
98. Robinson MB. The family of sodium-dependent glutamate transpor¬ters: A focus on the GLT-1/EAAT2 subtype. Neurochem Int 1998; 33: 479-91
99. Billups B, Rossi D, Oshima T, Warr O, Takahashi M, Sarantis M, et al. Physiological and pathological operation of glutamate transporters. Prog Brain Res 1998; 116: 45-57
100. Sonders MS, Amara SG. Channels in transporters. Curr Opin Neuro¬biol 1996; 6: 294-302
101. Takamori S, Rhee JS, Rosenmund C, Jahn R. Identification of a vesicular glutamate transporter that defines a glutamatergic phenotype in neurons. Nature 2000; 407: 189-94
102. Takamori S, Rhee JS, Rosenmund C, Jahn R. Identification of differentiation-Associated brain-specific phosphate transporter as a second vesicular glutamate transporter (VGLUT2). J Neurosci 2001; 21: RC182
103. Takamori S, Malherbe P, Broger C, Jahn R. Molecular cloning and functional characterization of human vesicular glutamate transporter 3. EMBO Rep 2002; 3: 798-803
104. Disbrow JK, Gershten MJ, Ruth JA. Uptake of L-[3H] glutamic acid by crude and purified synaptic vesicles from rat brain. Biochem Biophys Res Commun 1982; 108: 1221-7
105. Naito S, Ueda T. Characterization of glutamate uptake into synaptic vesicles. J Neurochem 1985; 44: 99-109
106. Koyama Y, Ishibashi T, Baba A. Increase in chloride-dependent L-glu¬tamate transport activity in synaptic membrane after in vitro ische¬mic treatment. J Neurochem 1995; 65: 1798-804
107. Lehre KP, Levy LM, Ottersen OP, Storm-Mathisen J, Danbolt NC. Dif¬ferential expression of two glial glutamate transporters in the rat bra¬in: Quantitative and immunocytochemical observations. J Neurosci 1995; 15: 1835-53
108. Bristol LA, Rothstein JD. Glutamate transporter gene expression in amyotrophic lateral sclerosis motor cortex. Ann Neurol 1996; 39: 676-9
109. Torp R, Lekieffre D, Levy LM, Haug FM, Danbolt NC, Meldrum BS, et al. Reduced postischemic expression of a glial glutamate transpor¬ter, GLT1, in the rat hippocampus. Exp Brain Res 1995; 103: 51-8
110. Palos TP, Ramachandran B, Boado R, Howard BD. Rat C6 and hu¬man astrocytic tumor cells express a neuronal type of glutamate transporter. Brain Res Mol Brain Res 1996; 37: 297-303
111. Figiel M, Engele J. Pituitary adenylate cyclase-Activating polypeptide (PACAP), a neuron-derived peptide regulating glial glutamate trans¬port and metabolism. J Neurosci 2000; 20: 3596-605
112. Gegelashvili G, Dehnes Y, Danbolt NC, Schousboe A. The high-Affinity glutamate transporters GLT1, GLAST, and EAAT4 are regulated via different signalling mechanisms. Neurochem Int 2000; 37: 163-70
113. Zelenaia O, Schlag BD, Gochenauer GE, Ganel R, Song W, Beesley JS, et al. Epidermal growth factor receptor agonists increase expres¬sion of glutamate transporter GLT-1 in astrocytes through pathways dependent on phosphatidylinositol 3-kinase and transcription factor NF-kappaB. Mol Pharmacol 2000; 57: 667-78
114. Li LB, Toan SV, Zelenaia O, Watson DJ, Wolfe JH, Rothstein JD, et al. Regulation of astrocytic glutamate transporter expression by Akt: Evidence for a selective transcriptional effect on the GLT-1/EAAT2 subtype. J Neurochem 2006; 97: 759-71
115. Sitcheran R, Gupta P, Fisher PB, Baldwin AS. Positive and negative regulation of EAAT2 by NF-kappaB: A role for N-myc in TNFalpha-con¬ trolled repression. EMBO J 2005; 24: 510-20
116. Ke S, Rabson AB, Germino JF, Gallo MA, Tian Y. Mechanism of suppression of cytochrome P-450 1A1 expression by tumor necro¬sis factor-Alpha and lipopolysaccharide. J Biol Chem 2001; 276: 39638-44
117. Levy LM, Lehre KP, Walaas SI, Storm-Mathisen J, Danbolt NC. Do¬wn-regulation of glial glutamate transporters after glutamatergic denervation in the rat brain. Eur J Neurosci 1995; 7: 2036-41
118. Ginsberg SD, Martin LJ, Rothstein JD. Regional deafferentation down-regulates subtypes of glutamate transporter proteins. J Neurochem 1995; 65: 2800-3
119. Benveniste H, Drejer J, Schousboe A, Diemer NH. Elevation of the extracellular concentrations of glutamate and aspartate in rat hippo¬campus during transient cerebral ischemia monitored by intracere¬bral microdialysis. J Neurochem 1984; 43: 1369-74
120. Sato H, Tamba M, Kuriyama-Matsumura K, Okuno S, Bannai S. Mole¬cular cloning and expression of human xCT, the light chain of amino acid transport system xc-. Antioxid Redox Signal 2000; 2: 665-71
121. Sato H, Kuriyama-Matsumura K, Hashimoto T, Sasaki H, Wang H, Ishii T, et al. Effect of oxygen on induction of the cystine transporter by bacterial lipopolysaccharide in mouse peritoneal macrophages. J Biol Chem 2001; 276: 10407-12
122. Lewerenz J, Maher P, Methner A. Regulation of xCT expression and system x (c) (-) function in neuronal cells. Amino Acids 2012; 42: 171-9
123. Lewerenz J, Maher P. Basal levels of eIF2alpha phosphorylation determine cellular antioxidant status by regulating ATF4 and xCT expression. J Biol Chem 2009; 284: 1106-15
124. Shih AY, Erb H, Sun X, Toda S, Kalivas PW, Murphy TH. Cystine/glu¬tamate exchange modulates glutathione supply for neuroprotection from oxidative stress and cell proliferation. J Neurosci 2006; 26: 10514-23
125. Sato H, Nomura S, Maebara K, Sato K, Tamba M, Bannai S. Tran¬scriptional control of cystine/glutamate transporter gene by amino acid deprivation. Biochem Biophys Res Commun 2004; 325: 109-16
126. Anderson CM, Swanson RA. Astrocyte glutamate transport: Review of properties, regulation, and physiological functions. Glia 2000; 32: 1-14
127. Duan S, Anderson CM, Stein BA, Swanson RA. Glutamate induces rapid upregulation of astrocyte glutamate transport and cell-surface expression of GLAST. J Neurosci 1999; 19: 10193-200
128. Correale DM, Kalandadze A, Zelenaia O, Robinson MB. Comparison of the regulation of cell surface expression of the GLT-1, GLAST, and EAAC1 subtypes of glutamate (Glu) transporters. Soc Neurosci Abs 1998; 24: 826.14
129. Trotti D, Peng JB, Dunlop J, Hediger MA. Inhibition of the glutamate transporter EAAC1 expressed in Xenopus oocytes by phorbol esters. Brain Res 2001; 914: 196-203
130. Gonzalez MI, Bannerman PG, Robinson MB. Phorbol myristate aceta¬te-dependent interaction of protein kinase Calpha and the neuronal glutamate transporter EAAC1. J Neurosci 2003; 23: 5589-93
131. Jackson M, Song W, Liu MY, Jin L, Dykes-Hoberg M, Lin CI, et al. Mo¬dulation of the neuronal glutamate transporter EAAT4 by two interac¬ting proteins. Nature 2001; 410: 89-93
132. Lin CI, Orlov I, Ruggiero AM, Dykes-Hoberg M, Lee A, Jackson M, et al. Modulation of the neuronal glutamate transporter EAAC1 by the interacting protein GTRAP3-18. Nature 2001; 410: 84-8
133. Trotti D, Danbolt NC, Volterra A. Glutamate transporters are oxidant-vulnerable: A molecular link between oxidative and excitotoxic neuro¬degeneration? Trends Pharmacol Sci 1998; 19: 328-34
134. Pogun S, Dawson V, Kuhar MJ. Nitric oxide inhibits [3H]-glutamate transport in synaptosomes. Synapse 1994; 18: 21-6
135. Volterra A, Trotti D, Tromba C, Floridi S, Racagni G. Glutamate uptake inhibition by oxygen free radicals in rat cortical astrocytes. J Neurosci 1994; 14: 2924-32
136. Chen Y, Ying W, Simma V, Copin JC, Chan PH, Swanson RA. Ove¬rexpression of Cu, Zn superoxide dismutase attenuates oxidative inhibition of astrocyte glutamate uptake. J Neurochem 2000; 75: 939-45
137. Fairman WA, Sonders MS, Murdoch GH, Amara SG. Arachidonic acid elicits a substrate-gated proton current associated with the glutama¬te transporter EAAT4. Nat Neurosci 1998; 1: 105-13
138. Zerangue N, Arriza JL, Amara SG, Kavanaugh MP. Differential modu¬lation of human glutamate transporter subtypes by arachidonic acid. J Biol Chem 1995; 270: 6433-5
139. Vandenberg RJ, Mitrovic AD, Johnston GA. Molecular basis for diffe¬rential inhibition of glutamate transporter subtypes by zinc ions. Mol Pharmacol 1998; 54: 189-96
140. Fahrig T. Receptor subtype involved and mechanism of norepinephri¬ne- induced stimulation of glutamate uptake into primary cultures of rat brain astrocytes. Glia 1993; 7: 212-8
141. Hansson E, Ronnback L. Receptor regulation of the glutamate, GABA and taurine high-Affinity uptake into astrocytes in primary culture. Brain Res 1991; 548: 215-21
142. Virgin CE Jr, Ha TP, Packan DR, Tombaugh GC, Yang SH, Horner HC, et al. Glucocorticoids inhibit glucose transport and glutamate uptake in hippocampal astrocytes: Implications for glucocorticoid neurotoxicity. J Neurochem 1991; 57: 1422-8
143. Faillace MP, Keller Sarmiento MI, Rosenstein RE. Melatonin effect on [3H]glutamate uptake and release in the golden hamster retina. J Neurochem 1996; 67: 623-8
144. Saransaari P, Lillrank SM, Oja SS. Phencyclidine treatment in mice: Effects on phencyclidine binding sites and glutamate uptake in cerebral cortex preparations. J Neural Transm Gen Sect 1993; 93: 47-59
145. Arriza JL, Fairman WA, Wadiche JI, Murdoch GH, Kavanaugh MP, Amara SG. Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex. J Neurosci 1994; 14: 5559-69
146. El Mestikawy S, Wallen-Mackenzie A, Fortin GM, Descarries L, Tru¬deau LE. From glutamate co-release to vesicular synergy: Vesicular glutamate transporters. Nat Rev Neurosci 2011; 12: 204-16
147. Juge N, Gray JA, Omote H, Miyaji T, Inoue T, Hara C, et al. Metabolic control of vesicular glutamate transport and release. Neuron 2010; 68: 99-112
148. Ni B, Rosteck PR Jr, Nadi NS, Paul SM. Cloning and expression of a cDNA encoding a brain-specific Na+-dependent inorganic phosphate cotransporter. Proc Natl Acad Sci U S A 1994; 91: 5607-11
149. Chang YF. Lysine metabolism in the human and the monkey: Demon¬stration of pipecolic acid formation in the brain and other organs. Neurochem Res 1982; 7: 577-88
150. Bannai S, Kitamura E. Role of proton dissociation in the transport of cystine and glutamate in human diploid fibroblasts in culture. J Biol Chem 1981; 256: 5770-2
151. Folbergrova J, Zhao Q, Katsura K, Siesjo BK. N-Tert-butyl-(alpha)- phenylnitrone improves recovery of brain energy state in rats follo¬wing transient focal ischemia. Proc Natl Acad Sci U S A 1995; 92: 5057-61
152. Koyama Y, Kimura Y, Hashimoto H, Matsuda T, Baba A. L-lactate inhibits L-cystine/L-glutamate exchange transport and decreases glu¬tathione content in rat cultured astrocytes. J Neurosci Res 2000; 59: 685-91
153. Lewerenz J, Dargusch R, Maher P. Lactacidosis modulates glutathio¬ne metabolism and oxidative glutamate toxicity. J Neurochem 2010; 113: 502-14
154. Rossi DJ, Oshima T, Attwell D. Glutamate release in severe brain ischaemia is mainly by reversed uptake. Nature 2000; 403: 316-21
155. Parpura V, Scemes E, Spray DC. Mechanisms of glutamate release from astrocytes: Gap junction "hemichannels", purinergic receptors and exocytotic release. Neurochem Int 2004; 45: 259-64
156. Dawson LA, Djali S, Gonzales C, Vinegra MA, Zaleska MM. Characte¬rization of transient focal ischemia-induced increases in extracellular glutamate and aspartate in spontaneously hypertensive rats. Brain Res Bull 2000; 53: 767-76
157. Katayama Y, Kawamata T, Tamura T, Hovda DA, Becker DP, Tsuboka¬wa T. Calcium-dependent glutamate release concomitant with massive potassium flux during cerebral ischemia in vivo. Brain Res 1991; 558: 136-40
158. Zeevalk GD, Davis N, Hyndman AG, Nicklas WJ. Origins of the extra¬cellular glutamate released during total metabolic blockade in the immature retina. J Neurochem 1998; 71: 2373-81
159. Li S, Mealing GA, Morley P, Stys PK. Novel injury mechanism in anoxia and trauma of spinal cord white matter: Glutamate release via reverse Na+-dependent glutamate transport. J Neurosci 1999; 19: RC16
160. Kobayashi S, Millhorn DE. Hypoxia regulates glutamate metabolism and membrane transport in rat PC12 cells. J Neurochem 2001; 76: 1935-48
161. Hsu L, Rockenstein E, Mallory M, Hashimoto M, Masliah E. Altered expression of glutamate transporters under hypoxic conditions in vitro. J Neurosci Res 2001; 64: 193-202
162. Sher PK, Hu SX. Increased glutamate uptake and glutamine syn¬thetase activity in neuronal cell cultures surviving chronic hypoxia. Glia 1990; 3: 350-7
163. Kelleher JA, Gregory GA, Chan PH. Effect of fructose-1,6- bisphospha¬te on glutamate uptake and glutamine synthetase activity in hypoxic astrocyte cultures. Neurochem Res 1994; 19: 209-15
164. Stanimirovic DB, Ball R, Durkin JP. Stimulation of glutamate uptake and Na,K-ATPase activity in rat astrocytes exposed to ischemia-like insults. Glia 1997; 19: 123-34
165. Fujimoto S, Katsuki H, Kume T, Kaneko S, Akaike A. Mechanisms of oxygen glucose deprivation-induced glutamate release from cerebro¬cortical slice cultures. Neurosci Res 2004; 50: 179-87
166. Jung HH, Lee JJ, Washington JM, Zuo Z. Inability of volatile anesthetics to inhibit oxygen-glucose deprivation-induced glutamate release via glutamate transporters and anion channels in rat cortico¬striatal slices. Brain Res 2008; 1227: 234-9
167. Bonde C, Noraberg J, Noer H, Zimmer J. Ionotropic glutamate recep¬tors and glutamate transporters are involved in necrotic neuronal cell death induced by oxygen-glucose deprivation of hippocampal slice cultures. Neuroscience 2005; 136: 779-94
168. Anderson CM, Bridges RJ, Chamberlin AR, Shimamoto K, Yasuda-Ka¬matani Y, Swanson RA. Differing effects of substrate and non-subs¬trate transport inhibitors on glutamate uptake reversal. J Neurochem 2001; 79: 1207-16
169. Djali S, Dawson LA. Characterization of endogenous amino acid efflux from hippocampal slices during chemically-induced ischemia. Neurochem Res 2001; 26: 135-43
170. Waagepetersen HS, Shimamoto K, Schousboe A. Comparison of effects of DL-Threo-(beta)-benzyloxyaspartate (DL-TBOA) and L-Trans-pyrrolidine-2,4- dicarboxylate (t-2,4-PDC) on uptake and release of [3H]D-Aspartate in astrocytes and glutamatergic neurons. Neurochem Res 2001; 26: 661-6
171. Selkirk JV, Stiefel TH, Stone IM, Naeve GS, Foster AC, Poulsen DJ. Over-expression of the human EAAT2 glutamate transporter within neurons of mouse organotypic hippocampal slice cultures leads to increased vulnerability of CA1 pyramidal cells. Eur J Neurosci 2005; 21: 2291-6
172. Bonde C, Sarup A, Schousboe A, Gegelashvili G, Noraberg J, Zimmer J. GDNF pre-Treatment aggravates neuronal cell loss in oxygen-glucose deprived hippocampal slice cultures: A possible effect of glutamate transporter up-regulation. Neurochem Int 2003; 43: 381-8
173. Yeh TH, Hwang HM, Chen JJ, Wu T, Li AH, Wang HL. Glutamate trans¬porter function of rat hippocampal astrocytes is impaired following the global ischemia. Neurobiol Dis 2005; 18: 476-83
174. Ketheeswaranathan P, Turner NA, Spary EJ, Batten TF, McColl BW, Saha S. Changes in glutamate transporter expression in mouse forebrain areas following focal ischemia. Brain Res 2011; 1418: 93-103
175. Bruhn T, Levy LM, Nielsen M, Christensen T, Johansen FF, Diemer NH. Ischemia induced changes in expression of the astrocyte glutamate transporter GLT1 in hippocampus of the rat. Neurochem Int 2000; 37: 277-85
176. Chen JC, Hsu-Chou H, Lu JL, Chiang YC, Huang HM, Wang HL, et al. Down-regulation of the glial glutamate transporter GLT-1 in rat hippo¬campus and striatum and its modulation by a group III metabotropic glutamate receptor antagonist following transient global forebrain ischemia. Neuropharmacology 2005; 49: 703-14
177. Raghavendra Rao VL, Rao AM, Dogan A, Bowen KK, Hatcher J, Ro¬thstein JD, et al. Glial glutamate transporter GLT-1 down-regulation precedes delayed neuronal death in gerbil hippocampus following transient global cerebral ischemia. Neurochem Int 2000; 36: 531-7
178. Kim DS, Kwak SE, Kim JE, Jung JY, Won MH, Choi SY, et al. Transient ischaemia affects plasma membrane glutamate transporter, not vesi¬cular glutamate transporter, expressions in the gerbil hippocampus. Anat Histol Embryol 2006; 35: 265-70
179. Rao VL, Dogan A, Bowen KK, Todd KG, Dempsey RJ. Antisense knoc¬kdown of the glial glutamate transporter GLT-1 exacerbates hippo¬campal neuronal damage following traumatic injury to rat brain. Eur J Neurosci 2001; 13: 119-28
180. Arranz AM, Gottlieb M, Perez-Cerda F, Matute C. Increased expres¬sion of glutamate transporters in subcortical white matter after tran¬sient focal cerebral ischemia. Neurobiol Dis 2010; 37: 156-65
181. Rao VL, Bowen KK, Dempsey RJ. Transient focal cerebral ischemia down-regulates glutamate transporters GLT-1 and EAAC1 expression in rat brain. Neurochem Res 2001; 26: 497-502
182. Sanchez-Mendoza E, Burguete MC, Castello-Ruiz M, Gonzalez MP, Roncero C, Salom JB, et al. Transient focal cerebral ischemia si¬gnificantly alters not only EAATs but also VGLUTs expression in rats: Relevance of changes in reactive astroglia. J Neurochem 2010; 113: 1343-55
183. Lobo AC, Gomes JR, Catarino T, Mele M, Fernandez P, Inacio AR, et al. Cleavage of the vesicular glutamate transporters under excitotoxic conditions. Neurobiol Dis 2011; 44: 292-303
184. Bevers MB, Neumar RW. Mechanistic role of calpains in postischemic neurodegeneration. J Cereb Blood Flow Metab 2008; 28: 655-73
185. Takagaki Y, Itoh Y, Aoki Y, Ukai Y, Yoshikuni Y, Kimura K. Inhibition of ischemia-induced fodrin breakdown by a novel phenylpyrimidine derivative NS-7: An implication for its neuroprotective action in rats with middle cerebral artery occlusion. J Neurochem 1997; 68: 2507-13
186. Michalski D, Hartig W, Krugel K, Edwards RH, Boddener M, Bohme L, et al. Region-specific expression of vesicular glutamate and GABA transporters under various ischaemic conditions in mouse forebrain and retina. Neuroscience 2013; 231: 328-44
187. Llorente IL, Perez-Rodriguez D, Burgin TC, Gonzalo-Orden JM, Mar¬tinez-Villayandre B, Fernandez-Lopez A. Age and meloxicam modify the response of the glutamate vesicular transporters (VGLUTs) after transient global cerebral ischemia in the rat brain. Brain Res Bull 2013; 94: 90-7
188. Harvey BK, Airavaara M, Hinzman J, Wires EM, Chiocco MJ, Howard DB, et al. Targeted over-expression of glutamate transporter 1 (GLT-1) reduces ischemic brain injury in a rat model of stroke. PLoS One 2011; 6: E22135
189. Mitani A, Tanaka K. Functional changes of glial glutamate transpor¬ter GLT-1 during ischemia: An in vivo study in the hippocampal CA1 of normal mice and mutant mice lacking GLT-1. J Neurosci 2003; 23: 7176-82
190. Namura S, Maeno H, Takami S, Jiang XF, Kamichi S, Wada K, et al. Inhibition of glial glutamate transporter GLT-1 augments brain edema after transient focal cerebral ischemia in mice. Neurosci Lett 2002; 324: 117-20
191. Yamashita A, Makita K, Kuroiwa T, Tanaka K. Glutamate transpor¬ters GLAST and EAAT4 regulate postischemic Purkinje cell death: An in vivo study using a cardiac arrest model in mice lacking GLAST or EAAT4. Neurosci Res 2006; 55: 264-70
192. Beschorner R, Simon P, Schauer N, Mittelbronn M, Schluesener HJ, Trautmann K, et al. Reactive astrocytes and activated microglial cells express EAAT1, but not EAAT2, reflecting a neuroprotective potential following ischaemia. Histopathology 2007; 50: 897-910
193. Castillo J, Davalos A, Naveiro J, Noya M. Neuroexcitatory amino acids and their relation to infarct size and neurological deficit in ischemic stroke. Stroke 1996; 27: 1060-5
194. Castillo J, Davalos A, Noya M. Progression of ischaemic stroke and excitotoxic aminoacids. Lancet 1997; 349: 79-83
195. Mallolas J, Hurtado O, Castellanos M, Blanco M, Sobrino T, Serena J, et al. A polymorphism in the EAAT2 promoter is associated with higher glutamate concentrations and higher frequency of progressing stroke. J Exp Med 2006; 203: 711-7
196. Aizenman E, Sinor JD, Brimecombe JC, Herin GA. Alterations of N-methyl-D-Aspartate receptor properties after chemical ischemia. J Pharmacol Exp Ther 2000; 295: 572-7
197. Tanaka H, Calderone A, Jover T, Grooms SY, Yokota H, Zukin RS, et al. Ischemic preconditioning acts upstream of GluR2 down-regulation to afford neuroprotection in the hippocampal CA1. Proc Natl Acad Sci U S A 2002; 99: 2362-7
198. Dave KR, Lange-Asschenfeldt C, Raval AP, Prado R, Busto R, Saul I, et al. Ischemic preconditioning ameliorates excitotoxicity by shifting glutamate/gamma-Aminobutyric acid release and biosynthesis. J Neurosci Res 2005; 82: 665-73
199. Romera C, Hurtado O, Mallolas J, Pereira MP, Morales JR, Romera A, et al. Ischemic preconditioning reveals that GLT1/EAAT2 glutamate transporter is a novel PPAR(gamma) target gene involved in neu¬roprotection. J Cereb Blood Flow Metab 2007; 27: 1327-38
200. Pradillo JM, Hurtado O, Romera C, Cardenas A, Fernandez-Tome P, Alonso-Escolano D, et al. TNFR1 mediates increased neuronal membrane EAAT3 expression after in vivo cerebral ischemic preconditioning. Neuroscience 2006; 138: 1171-8
201. Douen AG, Akiyama K, Hogan MJ, Wang F, Dong L, Chow AK, et al. Preconditioning with cortical spreading depression decreases intra¬ischemic cerebral glutamate levels and down-regulates excitatory amino acid transporters EAAT1 and EAAT2 from rat cerebal cortex plasma membranes. J Neurochem 2000; 75: 812-8
202. Cimarosti H, Jones NM, O'Shea RD, Pow DV, Salbego C, Beart PM. Hypoxic preconditioning in neonatal rat brain involves regulation of excitatory amino acid transporter 2 and estrogen receptor alpha. Neurosci Lett 2005; 385: 52-7
203. Liu YX, Zhang M, Liu LZ, Cui X, Hu YY, Li WB. The role of glutamate transporter-1a in the induction of brain ischemic tolerance in rats. Glia 2012; 60: 112-24
204. Romera C, Hurtado O, Botella SH, Lizasoain I, Cardenas A, Fernan¬dez-Tome P, et al. In vitro ischemic tolerance involves upregulation of glutamate transport partly mediated by the TACE/ADAM17-Tumor necrosis factor-Alpha pathway. J Neurosci 2004; 24: 1350-7
205. Kosugi T, Kawahara K, Yamada T, Nakajima T, Tanaka M. Functional significance of the preconditioning-induced down-regulation of gluta¬mate transporter GLT-1 in neuron/astrocyte co-cultures. Neurochem Res 2005; 30: 1109-16
206. Selkirk JV, Nottebaum LM, Vana AM, Verge GM, Mackay KB, Stiefel TH, et al. Role of the GLT-1 subtype of glutamate transporter in gluta¬mate homeostasis: The GLT-1-preferring inhibitor WAY-855 produces marginal neurotoxicity in the rat hippocampus. Eur J Neurosci 2005; 21: 3217-28
207. Chu K, Lee ST, Sinn DI, Ko SY, Kim EH, Kim JM, et al. Pharmacologi¬cal induction of ischemic tolerance by glutamate transporter-1 (EAAT2) upregulation. Stroke 2007; 38: 177-82
208. Rothstein JD, Patel S, Regan MR, Haenggeli C, Huang YH, Bergles DE, et al. Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Nature 2005; 433: 73-7
209. Lee SG, Su ZZ, Emdad L, Gupta P, Sarkar D, Borjabad A, et al. Me¬chanism of ceftriaxone induction of excitatory amino acid transpor¬ter-2 expression and glutamate uptake in primary human astrocytes. J Biol Chem 2008; 283: 13116-23
210. Lewerenz J, Klein M, Methner A. Cooperative action of glutamate transporters and cystine/glutamate antiporter system xc-protects from oxidative glutamate toxicity. J Neurochem 2006; 98: 916-25
211. Lewerenz J, Albrecht P, Tien ML, Henke N, Karumbayaram S, Korn¬blum HI, et al. Induction of Nrf2 and xCT are involved in the action of the neuroprotective antibiotic ceftriaxone in vitro. J Neurochem 2009; 111: 332-43
212. Fogal B, Li J, Lobner D, McCullough LD, Hewett SJ. System xc-Activity and astrocytes are necessary for interleukin-1(beta)-mediated hy¬poxic neuronal injury. J Neurosci 2007; 27: 10094-105
213. Sims B, Clarke M, Francillion L, Kindred E, Hopkins ES, Sontheimer H. Hypoxic preconditioning involves system xc-regulation in mouse neural stem cells. Stem Cell Res 2012; 8: 285-91
214. Seib TM, Patel SA, Bridges RJ. Regulation of the system x-C cystine/glutamate exchanger by intracellular glutathione levels in rat astrocy¬te primary cultures. Glia 2011; 59: 1387-401
215. Zhang Y, Jia D, Liu Z, Chen X, Hu X. Effects of amitriptyline on mo¬noamines of brain tissue in rats with focal cerebral ischemia- reper¬fusion injury. Chin Pharmacol Bull 2007; 23: 1077-80
216. Liu Z, Zhang Y, Jia D, Hu X, Chen X, Li J. Effects of amitriptyline on amino acids in ischemic areas in rats subjected to focal cerebral ischemia reperfusion. Chin Pharm J (China) 2008; 43: 1305
217. Tai YH, Tsai RY, Wang YH, Cherng CH, Tao PL, Liu TM, et al. Ami¬triptyline induces nuclear transcription factor-kappaB-dependent glutamate transporter upregulation in chronic morphine-infused rats. Neuroscience 2008; 153: 823-31
218. Baik HJ, Lee SA, Washington JM, Zuo ZY. Amitriptyline inhibits the activity of the rat glutamate transporter EAAT3 expressed in Xenopus oocytes. J Pharm Pharmacol 2009; 61: 577-81
219. Fumagalli E, Funicello M, Rauen T, Gobbi M, Mennini T. Riluzole enhances the activity of glutamate transporters GLAST, GLT1 and EAAC1. Eur J Pharmacol 2008; 578: 171-6
220. Heurteaux C, Laigle C, Blondeau N, Jarretou G, Lazdunski M. Alpha-linolenic acid and riluzole treatment confer cerebral protection and improve survival after focal brain ischemia. Neuroscience 2006; 137: 241-51
221. Siniscalchi A, Zona C, Sancesario G, D'Angelo E, Zeng YC, Mercuri NB, et al. Neuroprotective effects of riluzole: An electrophysiological and histological analysis in an in vitro model of ischemia. Synapse 1999; 32: 147-52
222. Samuni Y, Goldstein S, Dean OM, Berk M. The chemistry and biologi¬cal activities of N-Acetylcysteine. Biochim Biophys Acta 2013; 1830: 4117-29
223. Cotgreave IA. N-Acetylcysteine: Pharmacological considerations and experimental and clinical applications. Adv Pharmacol 1997; 38: 205-27
224. Zafarullah M, Li WQ, Sylvester J, Ahmad M. Molecular mechanisms of N-Acetylcysteine actions. Cell Mol Life Sci 2003; 60: 6-20
225. Moran MM, McFarland K, Melendez RI, Kalivas PW, Seamans JK. Cy¬stine/glutamate exchange regulates metabotropic glutamate recep¬tor presynaptic inhibition of excitatory transmission and vulnerability to cocaine seeking. J Neurosci 2005; 25: 6389-93
226. Tian H, Zhang Q, Li H, Zhang G. Antioxidant N-Acetylcysteine and AMPA/KA receptor antagonist DNQX inhibited mixed lineage kinase-3 activation following cerebral ischemia in rat hippocampus. Neurosci Res 2003; 47: 47-53
227. Khan M, Sekhon B, Jatana M, Giri S, Gilg AG, Sekhon C, et al. Admi¬nistration of N-Acetylcysteine after focal cerebral ischemia protects brain and reduces inflammation in a rat model of experimental stro¬ke. J Neurosci Res 2004; 76: 519-27
228. Zhang QG, Tian H, Li HC, Zhang GY. Antioxidant N-Acetylcysteine inhibits the activation of JNK3 mediated by the GluR6-PSD95-MLK3 signaling module during cerebral ischemia in rat hippocampus. Neu¬rosci Lett 2006; 408: 159-64
229. Won SJ, Yoo BH, Brennan AM, Shin BS, Kauppinen TM, Berman AE, et al. EAAC1 gene deletion alters zinc homeostasis and exacerbates neuronal injury after transient cerebral ischemia. J Neurosci 2010; 30: 15409-18
230. Jang BG, Won SJ, Kim JH, Choi BY, Lee MW, Sohn M, et al. EAAC1 gene deletion alters zinc homeostasis and enhances cortical neuronal injury after transient cerebral ischemia in mice. J Trace Elem Med Biol 2012; 26: 85-8
231. Cao L, Li L, Zuo Z. N-Acetylcysteine reverses existing cognitive impairment and increased oxidative stress in glutamate transporter type 3 deficient mice. Neuroscience 2012; 220: 85-9
232. Guan T, Qian Y, Tang X, Huang M, Huang L, Li Y, et al. Maslinic acid, a natural inhibitor of glycogen phosphorylase, reduces cerebral ische¬mic injury in hyperglycemic rats by GLT-1 up-regulation. J Neurosci Res 2011; 89: 1829-39
233. Qian Y, Guan T, Tang X, Huang L, Huang M, Li Y, et al. Maslinic acid, a natural triterpenoid compound from Olea europaea, protects cortical neurons against oxygen-glucose deprivation-induced injury. Eur J Pharmacol 2011; 670: 148-53.