Protease-activated receptor 1-dependent neuronal damage involves NMDA receptor function

Experimental Neurology

Volumn 217, Issue 1, 2009, Pages 136-146

  Hamill, Cecily E ^a   Mannaioni, Guido ^b   Lyuboslavsky, Polina ^a   Sastre, Aristide A ^a   Traynelis, Stephen F ^a  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF FLORENCE   (Italy)

Author keywords

Glutamate; Ischemia; N methyl D aspartate; Neuronal death; Neuroprotection; PAR; Protease activated receptor; Stroke; Thrombin

Indexed keywords

DIZOCILPINE; KETAMINE; N METHYL DEXTRO ASPARTIC ACID; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; PROTEINASE ACTIVATED RECEPTOR 1;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; CORPUS STRIATUM; MALE; MIDDLE CEREBRAL ARTERY; MIDDLE CEREBRAL ARTERY OCCLUSION; MOUSE; NERVE CELL LESION; NEUROPROTECTION; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; WILD TYPE;

ANALYSIS OF VARIANCE; ANIMALS; BRAIN INJURIES; CELLS, CULTURED; CORPUS STRIATUM; DISEASE MODELS, ANIMAL; DIZOCILPINE MALEATE; EMBRYO, MAMMALIAN; EXCITATORY AMINO ACID AGONISTS; EXCITATORY AMINO ACID ANTAGONISTS; FEMALE; GUANIDINES; INJECTIONS, INTRAVENTRICULAR; ISCHEMIC ATTACK, TRANSIENT; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; N-METHYLASPARTATE; NEURONS; OLIGOPEPTIDES; PREGNANCY; RATS; RECEPTOR, PAR-1; RECEPTORS, N-METHYL-D-ASPARTATE;

EID: 64249152749     PISSN: 00144886     EISSN: 10902430     Source Type: Journal    
DOI: 10.1016/j.expneurol.2009.01.023     Document Type: Article

References (108)

1. Arundine M., and Tymianski M. Molecular mechanisms of calcium-dependent neurodegeneration in excitotoxicity. Cell Calcium 34 (2003) 325-337
2. Ayata C., Ayata G., Hara H., Matthews R.T., Beal M.F., Ferrante R.J., Endres M., Kim A., Christie R.H., Waeber C., Huang P.L., Hyman B.T., and Moskowitz M.A. Mechanisms of reduced striatal NMDA excitotoxicity in type I nitric oxide synthase knock-out mice. J. Neurosci. 17 (1997) 6908-6917
3. Beal M.F., Kowall N.W., Swartz K.J., Ferrante R.J., and Martin J.B. Systemic approaches to modifying quinolinic acid striatal lesions in rats. J. Neurosci. 8 (1988) 3901-3908
4. Bernatowicz M.S., Klimas C.E., Hartl K.S., Peluso M., Allegretto N.J., and Seiler S.M. Development of potent thrombin receptor antagonist peptides. J. Med. Chem. 39 (1996) 4879-4887
5. Brady R.J., and Swann J.W. Ketamine selectively suppresses synchronized afterdischarges in immature hippocampus. Neurosci. Lett. 69 (1986) 143-149
6. Buller A.L., Larson H.C., Schneider B.E., Beaton J.A., Morrisett R.A., and Monaghan D.T. The molecular basis of NMDA receptor subtypes: native receptor diversity is predicted by subunit composition. J. Neurosci. 14 (1994) 5471-5484
7. Calabresi P., Centonze D., Pisani A., Sancesario G., Gubellini P., Marfia G.A., and Bernardi G. Striatal spiny neurons and cholinergic interneurons express differential ionotropic glutamatergic responses and vulnerability: implications for ischemia and Huntington's disease. Ann. Neurol. 43 (1998) 586-597
8. Cannon J.R., Keep R.F., Schallert T., Hua Y., Richardson R.J., and Xi G. Protease-activated receptor-1 mediates protection elicited by thrombin preconditioning in a rat 6-hydroxydopamine model of Parkinson's disease. Brain Res. 1116 (2006) 177-186
9. Cepeda C., Ariano M.A., Calvert C.R., Flores-Hernandez J., Chandler S.H., Leavitt B.R., Hayden M.R., and Levine M.S. NMDA receptor function in mouse models of Huntington disease. J. Neurosci. Res. 66 (2001) 525-539
10. Cheng T., Liu D., Griffin J.H., Fernandez J.A., Castellino F., Rosen E.D., Fukudome K., and Zlokovic B.V. Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotective. Nat. Med. 9 (2003) 338-342
11. Choi D.W., Koh J.Y., and Peters S. Pharmacology of glutamate neurotoxicity in cortical cell culture: attenuation by NMDA antagonists. J. Neurosci. 8 (1988) 185-196
12. Connolly A.J., Ishihara H., Kahn M.L., Farese Jr. R.V., and Coughlin S.R. Role of the thrombin receptor in development and evidence for a second receptor. Nature 381 (1996) 516-519
13. Coughlin S.R. How the protease thrombin talks to cells. Proc. Natl. Acad. Sci. U. S. A. 96 (1999) 11023-11027
14. Criswell H.E., Ming Z., Pleasant N., Griffith B.L., Mueller R.A., and Breese G.R. Macrokinetic analysis of blockade of NMDA-gated currents by substituted alcohols, alkanes and ethers. Brain Res 1015 (2004) 107-113
15. Cuomo O., Pignataro G., Gala R., Scorziello A., Gravino E., Piazza O., Tufano R., Di Renzo G., and Annunziato L. Antithrombin reduces ischemic volume, ameliorates neurologic deficits, and prolongs animal survival in both transient and permanent focal ischemia. Stroke 38 (2007) 3272-3279
16. Dirnagl U., Iadecola C., and Moskowitz M.A. Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci. 22 (1999) 391-397
17. Dogan A., Eras M.A., Rao V.L., and Dempsey R.J. Protective effects of memantine against ischemia-reperfusion injury in spontaneously hypertensive rats. Acta Neurochir. (Wien) 141 (1999) 1107-1113
18. Donovan F.M., Pike C.J., Cotman C.W., and Cunningham D.D. Thrombin induces apoptosis in cultured neurons and astrocytes via a pathway requiring tyrosine kinase and RhoA activities. J. Neurosci. 17 (1997) 5316-5326
19. Dravid S., Yuan H., Erreger K., Lyuboslavsky P., Le P., Almonte A., Barber J., Nicholson K., French A., Balster R., Murray T.F., and Traynelis S.F. Proton sensitivity of NMDA receptor channel blockers. J. Physiol. 581 (2007) 107-128
20. Dunah A.W., and Standaert D.G. Subcellular segregation of distinct heteromeric NMDA glutamate receptors in the striatum. J. Neurochem. 85 (2003) 935-943
21. Duncan C.P., Seidler F.J., and Slotkin T.A. Effects of MK-801 on DNA synthesis in neonatal rat brain regions under normoxic and hypoxic conditions. Brain. Res. Dev. Brain Res. 58 (1991) 67-71
22. Erreger K., Chen P., Wyllie D.J.A., and Traynelis S.F. Glutamate receptor gating. Crit. Rev. Neurobiol. 16 (2004) 187-224
23. Friedmann I., Yoles E., and Schwartz M. Thrombin attenuation is neuroprotective in the injured rat optic nerve. J. Neurochem. 76 (2001) 641-649
24. Fujimoto S., Katsuki H., Ohnishi M., Takagi M., Kume T., and Akaike A. Plasminogen potentiates thrombin cytotoxicity and contributes to pathology of intracerebral hemorrhage in rats. J. Cereb. Blood Flow Metab. 28 (2008) 506-515
25. Galbicka G., Kautz M.A., and Jagers T. Behavioral effects of enantiomers of dizocilpine under two "counting" procedures in rats. Pharmacol. Biochem. Behav. 49 (1994) 943-948
26. Gingrich M.B., Junge C.E., Lyuboslavsky P., and Traynelis S.F. Potentiation of NMDA receptor function by the serine protease thrombin. J. Neurosci. 20 (2000) 4582-4595
27. Gingrich M.B., and Traynelis S.F. Serine proteases and brain damage - is there a link?. Trends Neurosci. 23 (2000) 399-407
28. Guo H., Liu D., Gelbard H., Cheng T., Insalaco R., Fernandez J.A., Griffin J.H., and Zlokovic B.V. Activated protein C prevents neuronal apoptosis via protease activated receptors 1 and 3. Neuron 41 (2004) 563-572
29. Hamill C.E., Goldshmidt A., Nicole O., Brat D., and Traynelis S.F. Glial reactivity following damage: implications for scar formation and neuronal recovery. Clin. Neurosurg. 52 (2005) 29-44
30. Harrison N.L., and Simmonds M.A. Quantitative studies on some antagonists of N-methyl d-aspartate in slices of rat cerebral cortex. Br. J. Pharmacol. 84 (1985) 381-391
31. Hawkins R.L., and Seeds N.W. Effect of proteases and their inhibitors on neurite outgrowth from neonatal mouse sensory ganglia in culture. Brain Res. 398 (1986) 63-70
32. Henrich-Noack P., Riek-Burchardt M., Baldauf K., Reiser G., and Reymann K.G. Focal ischemia induces expression of protease-activated receptor1 (PAR1) and PAR3 on microglia and enhances PAR4 labeling in the penumbra. Brain Res. 1070 (2006) 232-241
33. Hollenberg M.D., Saifeddine M., al-Ani B., and Kawabata A. Proteinase-activated receptors: structural requirements for activity, receptor cross-reactivity, and receptor selectivity of receptor-activating peptides. Can. J. Physiol. Pharmacol. 75 (1997) 832-841
34. Ishida Y., Nagai A., Kobayashi S., and Kim S.U. Upregulation of protease-activated receptor-1 in astrocytes in Parkinson disease: astrocyte-mediated neuroprotection through increased levels of glutathione peroxidase. J. Neuropathol. Exp. Neurol. 65 (2006) 66-77
35. Jalink K., and Moolenaar W.H. Thrombin receptor activation causes rapid neural cell rounding and neurite retraction independent of classic second messengers. J. Cell. Biol. 118 (1992) 411-419
36. Jiang Y., Wum J., Hua Y., Keep R.F., Xiang J., Hoff J.T., and Xi G. Thrombin-receptor activation and thrombin-induced brain tolerance. J. Cereb. Blood Flow Metab. 22 (2002) 404-410
37. Jin Y.J., Mima T., Raicu V., Park K.C., and Shimizu K. Combined argatroban and edaravone caused additive neuroprotection against 15 min of forebrain ischemia in gerbils. Neurosci. Res. 43 (2002) 75-79
38. Junge C.E., Sugawara T., Mannaioni G., Alagarsamy S., Conn P.J., Brat D.J., Chan P.H., and Traynelis S.F. The contribution of protease-activated receptor 1 to neuronal damage caused by transient focal cerebral ischemia. Proc. Natl. Acad. Sci. U. S. A. 100 (2003) 13019-13024
39. Junge C.E., Lee C.J., Hubbard K.B., Zhang Z., Olson J.J., Hepler J.R., Brat D.J., and Traynelis S.F. Protease-activated receptor-1 in human brain: localization and functional expression in astrocytes. Exp. Neurol. 188 (2004) 94-103
40. Kant G.J., Wright W.L., Robinson III T.N., and D'Angelo C.P. Effects of MK-801 on learning and memory as assessed using a novel water maze. Pharmacol. Biochem. Behav. 39 (1991) 479-485
41. Karabiyikoglu M., Hua Y., Keep R.F., Ennis S.R., and Xi G. Intracerebral hirudin injection attenuates ischemic damage and neurologic deficits without altering local cerebral blood flow. J. Cereb. Blood Flow Metab. 24 (2004) 159-166
42. Kawabata A., Saifeddine M., Al-Ani B., Leblond L., and Hollenberg M.D. Evaluation of proteinase-activated receptor-1 (PAR1) agonists and antagonists using a cultured cell receptor desensitization assay: activation of PAR2 by PAR1-targeted ligands. J. Pharmacol. Exp. Ther. 288 (1999) 358-370
43. Kawaguchi M., Furuya H., and Patel P.M. Neuroprotective effects of anesthetic agents. J. Anesth. 19 (2005) 150-156
44. Klarenbach S.W., Chipiuk A., Nelson R.C., Hollenberg M.D., and Murray A.G. Differential actions of PAR2 and PAR1 in stimulating human endothelial cell exocytosis and permeability: the role of Rho-GTPases. Circ. Res. 92 (2003) 272-278
45. Koh J.Y., and Choi D.W. Quantitative determination of glutamate mediated cortical neuronal injury in cell culture by lactate dehydrogenase efflux assay. J. Neurosci. Methods 20 (1987) 83-90
46. Kuppenbender K.D., Standaert D.G., Feuerstein T.J., Penney Jr. J.B., Young A.B., and Landwehrmeyer G.B. Expression of NMDA receptor subunit mRNAs in neurochemically identified projection and interneurons in the human striatum. J. Comp. Neurol. 419 (2000) 407-421
47. Leavitt B.R., Raamsdonk J.M., Shehadeh J., Fernandes H., Murphy Z., Graham R.K., Wellington C.L., Raymond L.A., and Hayden M.R. Wild-type huntingtin protects neurons from excitotoxicity. J. Neurochem. 96 (2006) 1121-1129
48. Lee C.J., Mannaioni G., Yuan H., Woo D.H., Gingrich M.B., and Traynelis S.F. Astrocytic control of synaptic NMDA receptors. J. Physiol. 581 (2007) 1057-1081
49. Lees K.R. Cerestat and other NMDA antagonists in ischemic stroke. Neurology 49 (1997) S66-69
50. 2+ prevents neurotoxicity. Brain. Res. 598 (1992) 196-202
51. Lipton S.A. Molecular mechanisms of trauma-induced neuronal degeneration. Curr. Opin. Neurol. Neurosurg. 6 (1993) 588-596
52. Liu L.W., Vu T.K., Esmon C.T., and Coughlin S.R. The region of the thrombin receptor resembling hirudin binds to thrombin and alters enzyme specificity. J. Biol. Chem. 266 (1991) 16977-16980
53. Macfarlane S.R., Seatter M.J., Kanke T., Hunter G.D., and Plevin R. Proteinase-activated receptors. Pharmacol. Rev. 53 (2001) 245-282
54. Mannaioni G., Goldshmidt A., Hamill C.E., Yuan H., Mullasseril P., Hubbard K.B., Junge C.E., Lee C.J., Yepes M., Hepler J.R., and Traynelis S.F. Plasmin potentiates synaptic NMDA receptor function in rat hippocampal neurons through activation of PAR1. J. Biol. Chem. 283 (2008) 20600-20611
55. Masada T., Xi G., Hua Y., and Keep R.F. The effects of thrombin preconditioning on focal cerebral ischemia in rats. Brain Res. 867 (2000) 173-179
56. Matsuoka H., and Hamada R. Role of thrombin in CNS damage associated with intracerebral haemorrhage: opportunity for pharmacological intervention?. CNS Drugs 16 (2002) 509-516
57. McDonald J.W., Roeser N.F., Silverstein F.S., and Johnston M.V. Quantitative assessment of neuroprotection against NMDA-induced brain injury. Exp. Neurol. 106 (1989) 289-296
58. Meldrum B.S., Evans M.C., Swan J.H., and Simon R.P. Protection against hypoxic/ischaemic brain damage with excitatory amino acid antagonists. Med. Biol. 65 (1987) 153-157
59. Miyabe M., Kirsch J.R., Nishikawa T., Koehler R.C., and Traystman R.J. Comparative analysis of brain protection by N-methyl-d-aspartate receptor antagonists after transient focal ischemia in cats. Crit. Care Med. 25 (1997) 1037-1043
60. Monard D., Niday E., Limat A., and Solomon F. Inhibition of protease activity can lead to neurite extension in neuroblastoma cells. Prog. Brain Res. 58 (1983) 359-364
61. Mosnier L.O., and Griffin J.H. Inhibition of staurosporine-induced apoptosis of endothelial cells by activated protein C requires protease-activated receptor-1 and endothelial cell protein C receptor. Biochem. J. 373 (2003) 65-70
62. Niclou S.P., Suidan H.S., Pavlik A., Vejsada R., and Monard D. Changes in the expression of protease-activated receptor 1 and protease nexin-1 mRNA during rat nervous system development and after nerve lesion. Eur. J. Neurosci. 10 (1998) 1590-1607
63. Nicole O., Goldshmidt A., Hamill C.E., Sorensen S.D., Sastre A., Lyuboslavsky P., Hepler J.R., McKeon R.J., and Traynelis S.F. Activation of protease-activated receptor-1 triggers astrogliosis after brain injury. J. Neurosci. 25 (2005) 4319-4329
64. Ogata J., Shiraishi M., Namba T., Smothers C.T., Woodward J.J., and Harris R.A. Effects of anesthetics on mutant N-methyl-d-aspartate receptors expressed in Xenopus oocytes. J. Pharmacol. Exp. Ther. 318 (2006) 434-443
65. Olson E.E., Lyuboslavsky P., Traynelis S.F., and McKeon R.J. PAR-1 deficiency protects against neuronal damage and neurologic deficits after unilateral cerebral hypoxia/ischemia. J. Cereb. Blood Flow Metab. 24 (2004) 964-971
66. Ozden S., and Isenmann S. Neuroprotective properties of different anesthetics on axotomized rat retinal ganglion cells in vivo. J. Neurotrauma 21 (2004) 73-82
67. Park C.K., Nehls D.G., Graham D.I., Teasdale G.M., and McCulloch J. The glutamate antagonist MK-801 reduces focal ischemic brain damage in the rat. Ann Neurol 24 (1988) 543-551
68. Portera-Cailliau C., Hedreen J.C., Price D.L., and Koliatsos V.E. Evidence for apoptotic cell death in Huntington disease and excitotoxic animal models. J. Neurosci. 15 (1995) 3775-3787
69. Qin Z.H., Wang Y., and Chase T.N. Stimulation of N-methyl-d-aspartate receptors induces apoptosis in rat brain. Brain Res. 725 (1996) 166-176
70. Ramos-Mandujano G., Vazquez-Juarez E., Hernandez-Benitez R., and Pasantes-Morales H. Thrombin potently enhances swelling-sensitive glutamate efflux from cultured astrocytes. Glia 55 (2007) 917-925
71. Riek-Burchardt M., Striggow F., Henrich-Noack P., Reiser G., and Reymann K.G. Increase of prothrombin-mRNA after global ischemia in rats, with constant expression of protease nexin-1 and protease-activated receptors. Neurosci. Lett 329 (2002) 181-184
72. Rohatgi T., Henrich-Noack P., Sedehizade F., Goertler M., Wallesch C.W., Reymann K.G., and Reiser G. Transient focal ischemia in rat brain differentially regulates mRNA expression of protease-activated receptors 1 to 4. J.Neurosci.Res. 75 (2004) 273-279
73. Roussel S., Pinard E., and Seylaz J. Effect of MK-801 on focal brain infarction in normotensive and hypertensive rats. Hypertension 19 (1992) 40-46
74. Ruf W. PAR1 signaling: more good than harm?. Nat. Med. 9 (2003) 258-260
75. Sheehan J.J., and Tsirka S.E. Fibrin-modifying serine proteases thrombin, tPA, and plasmin in ischemic stroke: a review. Glia 50 (2005) 340-350
76. Shibata M., Kumar S.R., Amar A., Fernandez J.A., Hofman F., Griffin J.H., and Zlokovic B.V. Anti-inflammatory, antithrombotic, and neuroprotective effects of activated protein C in a murine model of focal ischemic stroke. Circulation 103 (2001) 1799-1805
77. Shigetomi E., Bowser D.N., Sofroniew M.V., and Khakh B.S. Two forms of astrocyte calcium excitability have distinct effects on NMDA receptor-mediated slow inward currents in pyramidal neurons. J.Neurosci. 28 (2008) 6659-6663
78. Silverman J., and Muir III W.W. A review of laboratory animal anesthesia with chloral hydrate and chloralose. Lab. Anim. Sci. 43 (1993) 210-216
79. 2+ mobilization, and apoptosis. J. Neurobiol. 48 (2001) 87-100
80. 2+ homeostasis and sensitivity to glucose deprivation-induced injury. J. Neurosci. 15 (1995) 5840-5850
81. Snider R.M., and Richelson E. Thrombin stimulation of guanosine 3′,5′-monophosphate formation in murine neuroblastoma cells (clone N1E-115). Science 221 (1983) 566-568
82. Snider R.M., McKinney M., Fenton II J.W., and Richelson E. Activation of cyclic nucleotide formation in murine neuroblastoma N1E-115 cells by modified human thrombins. J. Biol. Chem. 259 (1984) 9078-9081
83. Sorensen S.D., Nicole O., Peavy R.D., Montoya L.M., Lee C.J., Murphy T.J., Traynelis S.F., and Hepler J.R. Common signaling pathways link activation of murine PAR-1, LPA, and S1P receptors to proliferation of astrocytes. Mol. Pharmacol. 64 (2003) 1199-1209
84. Standaert D.G., Friberg I.K., Landwehrmeyer G.B., Young A.B., and Penney Jr. J.B. Expression of NMDA glutamate receptor subunit mRNAs in neurochemically identified projection and interneurons in the striatum of the rat. Brain Res. Mol. Brain Res. 64 (1999) 11-23
85. Striggow F., Riek M., Breder J., Henrich-Noack P., Reymann K.G., and Reiser G. The protease thrombin is an endogenous mediator of hippocampal neuroprotection against ischemia at low concentrations but causes degeneration at high concentrations. Proc. Natl. Acad. Sci. U. S. A. 97 (2000) 2264-2269
86. Striggow F., Riek-Burchardt M., Kiesel A., Schmidt W., Henrich-Noack P., Breder J., Krug M., Reymann K.G., and Reiser G. Four different types of protease-activated receptors are widely expressed in the brain and are up-regulated in hippocampus by severe ischemia. Eur. J. Neurosci. 14 (2001) 595-608
87. Suidan H.S., Stone S.R., Hemmings B.A., and Monard D. Thrombin causes neurite retraction in neuronal cells through activation of cell surface receptors. Neuron 8 (1992) 363-375
88. Suo Z., Wu M., Ameenuddin S., Anderson H.E., Zoloty J.E., Citron B.A., Andrade-Gordon P., and Festoff B.W. Participation of protease-activated receptor-1 in thrombin-induced microglial activation. J. Neurochem. 80 (2002) 655-666
89. Suo Z., Citron B.A., and Festoff B.W. Thrombin: a potential proinflammatory mediator in neurotrauma and neurodegenerative disorders. Curr. Drug Targets Inflamm. Allergy 3 (2004) 105-114
90. Swan J.H., and Meldrum B.S. Protection by NMDA antagonists against selective cell loss following transient ischaemia. J. Cereb. Blood Flow Metab. 10 (1990) 343-351
91. Thomson A.M., West D.C., and Lodge D. An N-methylaspartate receptor-mediated synapse in rat cerebral cortex: a site of action of ketamine?. Nature 313 (1985) 479-481
92. Trejo J. Protease-activated receptors: new concepts in regulation of G protein-coupled receptor signaling and trafficking. J. Pharmacol. Exp. Ther. 307 (2003) 437-442
93. Traynelis S.F., and Trejo J. Protease receptor signaling: new roles and regulatory mechanisms. Curr. Opin. Hematol. 14 (2007) 230-235
94. Turgeon V.L., Lloyd E.D., Wang S., Festoff B.W., and Houenou L.J. Thrombin perturbs neurite outgrowth and induces apoptotic cell death in enriched chick spinal motoneuron cultures through caspase activation. J. Neurosci. 18 (1998) 6882-6891
95. Uematsu D., Araki N., Greenberg J.H., Sladky J., and Reivich M. Combined therapy with MK-801 and nimodipine for protection of ischemic brain damage. Neurology 41 (1991) 88-94
96. Vaughan P.J., Pike C.J., Cotman C.W., and Cunningham D.D. Thrombin receptor activation protects neurons and astrocytes from cell death produced by environmental insults. J. Neurosci. 15 (1995) 5389-5401
97. Vivien D., and Buisson A. Serine protease inhibitors: novel therapeutic targets for stroke. J. Cereb. Blood Flow Metab. 20 (2000) 755-764
98. Vu T.K., Hung D.T., Wheaton V.I., and Coughlin S.R. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell 64 (1991) 1057-1068
99. Wang C.X., and Shuaib A. NMDA/NR2B selective antagonists in the treatment of ischemic brain injury. Curr. Drug Targets CNS Neurol. Disord. 4 (2005) 143-151
100. Wang H., Ubl J.J., and Reiser G. Four subtypes of protease-activated receptors, co-expressed in rat astrocytes, evoke different physiological signaling. Glia 37 (2002) 53-63
101. Warner M.A., Neill K.H., Nadler J.V., and Crain B.J. Regionally selective effects of NMDA receptor antagonists against ischemic brain damage in the gerbil. J. Cereb. Blood Flow Metab. 11 (1991) 600-610
102. Weinstein J.R., Gold S.J., Cunningham D.D., and Gall C.M. Cellular localization of thrombin receptor mRNA in rat brain: expression by mesencephalic dopaminergic neurons and codistribution with prothrombin mRNA. J. Neurosci. 15 (1995) 2906-2919
103. Whetsell Jr. W.O. Current concepts of excitotoxicity. J. Neuropathol. Exp. Neurol. 55 (1996) 1-13
104. Wong E.H., Kemp J.A., Priestley T., Knight A.R., Woodruff G.N., and Iversen L.L. The anticonvulsant MK-801 is a potent N-methyl-d-aspartate antagonist. Proc. Natl. Acad. Sci. USA 83 (1986) 7104-7108
105. Xi G., Reiser G., and Keep R.F. The role of thrombin and thrombin receptors in ischemic, hemorrhagic and traumatic brain injury: deleterious or protective?. J. Neurochem. 84 (2003) 3-9
106. Xue M., Hollenberg M.D., and Yong V.W. Combination of thrombin and matrix metalloproteinase-9 exacerbates neurotoxicity in cell culture and intracerebral hemorrhage in mice. J. Neurosci. 26 (2006) 10281-10291
107. Yamakura T., Askalany A.R., Petrenko A.B., Kohno T., Baba H., and Sakimura K. The NR3B subunit does not alter the anesthetic sensitivities of recombinant N-methyl-d-aspartate receptors. Anesth. Analg. 100 (2005) 1687-1692
108. Yang J., and Zorumski C.F. Effects of isoflurane on N-methyl-d-aspartate gated ion channels in cultured rat hippocampal neurons. Ann. N.Y. Acad. Sci. 625 (1991) 287-289