Effects of the novel NMDA antagonists CP-98,113, CP-101,581 and CP- 101,606 on cognitive function and regional cerebral edema following experimental brain injury in the rat

Journal of Neurotrauma

Volumn 14, Issue 4, 1997, Pages 211-222

  Okiyama, Koichi ^a   Smith, Douglas H ^a   White, W Frost ^b   Richter, Karl ^b   Mcintosh, Tracy K ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United States)

Author keywords

fluid percussion brain injury; Ifenprodil; memory; NMDA receptor blocker

Indexed keywords

DIMETHYL SULFOXIDE; IFENPRODIL; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; TRAXOPRODIL; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN EDEMA; BRAIN INJURY; COGNITION; CONTROLLED STUDY; INTRAPERITONEAL DRUG ADMINISTRATION; MALE; MAZE TEST; NEUROTRANSMISSION; NONHUMAN; RAT; SPATIAL MEMORY; SUBCUTANEOUS DRUG ADMINISTRATION;

EID: 0030925812     PISSN: 08977151     EISSN: None     Source Type: Journal    
DOI: 10.1089/neu.1997.14.211     Document Type: Article

References (105)

1. ADEAGBO, A.S.O. and MAGBAGBEOLA, A.O. (1985). Pharmacological actions of ifenprodil on the rat isolated anococcygeus muscle. J. Pharm. Pharmacol. 37, 833-835.
2. BAETHMANN, A., MAIER-HAUFF, K., SCHURER, L., et al. (1989). Release of glutamate and of free fatty acids in vasogenic brain edema. J. Neurosurg. 70, 578-591.
3. BARNES, C.A. (1988). Spatial learning and memory processes: the search for their neurobiological mechanisms in the rat. TINS 11, 163-169.
4. BENTUÉ-FERRER, D., DECOMBE, R., REYMANN, J.-M., SCHATZ, C., and ALLAIN, H. (1990). Progress in understanding the pathophysiology of cerebral ischemia: the amitrine-raubasine approach. Clin. Neuropharmacol. 13 (Suppl. 3), 9-25.
5. BUCHAN, A. (1992). Advances in cerebral ischemia: Experimental approaches. Neurol. Clin. 10, 49-61.
6. BULLOCK, R. and FUJISAWA, H. (1994). Do excitatory amino acids cause brain damage after severe head injury? J. Neurotrauma 11, 214-219.
7. BULLOCK, R., MAXWELL, W.L., GRAHAM, D.I., TEASDALE, G.M., and ADAMS, J.H. (1991). Glial swelling following human cerebral contusion: an ultrastructural study. J. Neurol. Neurosurg. Psychiatry 54, 427-432.
8. CARRON, C., JULLIEN, A., and BUCHER, B. (1971). Synthesis and pharmacological properties of a series of 2-piperidino alkanol derivatives. Arzeim. Forsch./Drug. Res. 21, 1992-1998.
9. CARTER, C., BENAVIDES, J., LEGENDRE, P., et al. (1988). Ifenprodil and SL 82.0715 as cerebral anti-ischemic agents. II. Evidence for N-methyl-D-aspartate receptor antagonist properties. J. Pharmacol. Exp. Ther. 247, 1222-1232.
10. CARTER, C., KENNETH, G., LLOID, K.G., ZIVKOVIC, B., and SCATTON, B. (1990). Ifenprodil and SL 82.0715 as cerebral anti-ischemic agents. III. Evidence for antagonistic effects at the polyamine modulatory site within the N-methyl-D-aspartate receptor complex. J. Pharmacol. Exp. Ther. 253, 475-482.
11. CHAN, P.H. and CHU, L. (1990). Mechanisms underlying glutamate-induced swelling of astrocytes in primary culture. Acta. Neurochir. (Suppl.) 51, 7-10.
12. CHOI, D.W. (1987). Ionic dependence of glutamate neurotoxicity. J. Neurosci. 7, 369-379.
13. CHOI, D.W., KOH, J., and PETERS, S. (1988). Pharmacology of glutamate neurotoxicity in cortical cell culture: attenuation by NMDA antagonists. J. Neurosci. 8, 185-196.
14. CHOI, D., MAULUCCI-GEDDE, M., and KRIEGSTEIN, A.R. (1987). Glutamate neurotoxicity in cortical cell culture. J. Neurosci. 7, 357-368.
15. CHOI, D. and ROTHMAN, S.M. (1990). The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death. Ann. Rev. Neurosci. 13, 171-182.
16. CLIFFORD, D.B., ZORUMSKI, C.F., and OLNEY, J.W. (1989). Ketamine and MK-801 prevent degeneration of thalamic neurons induced by focal cortical seizures. Exp. Neurol. 105, 272-279.
17. COLLINGRIDGE, G.L., and BLISS, T.V.P. (1987). NMDA receptors-their role in long-term potentiation. Trends. Neurosci. 10, 288-293.
18. COOK, P. and JAMES, I. (1981a). Cerebral vasodilators (first of two parts). N. Engl. J. Med. 305, 1508-1513.
19. COOK, P. and JAMES, I. (1981b). Cerebral vasodilators (second of two parts). N. Engl. J. Med. 305, 1560-1564.
20. CORTEZ, S.C., MCINTOSH, T.K., and NOBLE, L. (1989). Experimental fluid percussion brain injury: Vascular disruption and neuronal and glial alterations. Brain Res. 482, 271-282.
21. DELAGE, I., DUVERGER, D., GOTTI, B., and MACKENZIE, E.T. (1981). Correlation of local blood flow, glucose consumption and probability of necrosis following a middle cerebral artery occlusion in the cat. Eur. Neurol. 20, 258-264.
22. DIETRICH, W.D., ALONSO, O., and HALLEY, M. (1994). Early microvascular and neuronal consequences of traumatic brain injury: A light and electron microscopic study in rats. J. Neurotrauma 11, 289-301.
23. FADEN, A.I., DEMEDIUK, P., PANTER, S.S., and VINK, R. (1989). The role of excitatory amino acids and NMDA receptors in traumatic brain injury. Science 244, 789-800.
24. FADEN, A.I. and SIMON, R.P. (1988). The potential role for excitotoxins in the pathophysiology of spinal cord injury. Ann. Neurol. 235, 623-626.
25. FLOOD, J.F., BAKER, M.L., and DAVIS, J.L. (1990). Modulation of memory processing by glutamic acid receptor agonists and antagonists. Brain Res. 521, 197-202.
26. FOSTER, A.C., GILL, R., KEMP, J.A., and WOODRUFF, G.N. (1987). Systemic administration of MK-801 prevents N-methyl-D-aspartate-induced neuronal degeneration in the rat brain. Neurosci. Lett. 76, 307-311.
27. GLOBUS, M.Y.-T., ALONSO, O., DIETRICH, W.D., BUSTO, R., and GINSBERG, M.D. (1985). Glutamate release and free radical production following brain injury: Effects of posttraumatic hypothermia. J. Neurochem. 65, 1704-1711.
28. GOTTI, B., DUVERGER, D., BERTIN, J., et al. (1988). Ifenprodil and SL 82.0715 as cerebral anti-ischemic agents. I. Evidence for efficacy in models of focal cerebral ischemia. J. Pharmacol. Exp. Ther. 247, 1211-1221.
29. HAMM, R.J., DIXON, C.E., GBADEBO, D.M., et al. (1992). Cognitive deficits following traumatic brain injury by controlled cortical impact. J. Neurotrauma 9, 11-20.
30. HAMM, R.J., LYETH, B.G., JENKINS, L.W., O'DELL, D.M., and PIKE, B.R. (1993). Selective cognitive impairment following traumatic brain injury in rats. Behav. Brain Res. 59, 169-173.
31. HAPPERT, J.L., CATEL, P., PILARDEAU, P., and LOISEL, J.C. (1976). Emploi du Vadilex* dans le traitement des insuffisants vasulaires célébraux. Vie. Méd. 57, 2334-2336.
32. HAYES, R.L., JENKINS, L.W., LYETH, B.G., et al. (1988a). Pretreatment with phencyclidine, an N-methyl-D-aspartate antagonist, attenuates long-term behavioral deficits in the rat produced by traumatic brain injury. J. Neurotrauma 5, 259-274.
33. HAYES, R.L., MILLER, L.P., LYETH, B.G., et al. (1988b). Traumatic brain injury produces transient reduction in binding to excitatory amino acid receptor subtypes. Soc. Neurosci. Abstr. 14, 1153.
34. HAYES, R.L., JENKINS, L.W., and LYETH, B.G. (1992). Neurotransmitter-mediated mechanisms of traumatic brain injury - acetylcholine and excitatory amino acids. J. Neurotrauma 9, S173-S187.
35. HICKS, R.R., SMITH, D.H., LOWENSTEIN, D.H., SAINT MARIE, R.L., and MCINTOSH, T.K. (1993). Mild experimental brain injury in the rat induces cognitive deficits associated with regional neuronal loss in the hippocampus. J. Neurotrauma 10, 405-414.
36. HICKS, R.R., SMITH, D.H., and MCINTOSH, T.K. (1994). Kynurenate is neuroprotective following experimental brain injury in the rat. Brain. Res. 655, 91-96.
37. HICKS, R.R., SMITH, D.H., and MCINTOSH, T.K. (1995). Temporal response and effects of excitatory amino acid antagonism on microtubule-associated protein 2 immunoreactivity following experimental brain injury in rats. Brain. Res. 678, 151-160.
38. HICKS, R.R., SOARES, H.D., SMITH, D.H., and MCINTOSH, T.K. (1996). Temporal and spatial characterization of neuronal injury following lateral fluid-percussion brain injury in the rat. Acta. Neuropathol. 91, 236-246.
39. HONDA, H. and SAKAI, Y. (1987). The mode of action of ifenprodil tartate in isolated canine cerebral and femoral arteries. Arch. Int. Pharmacodyn. 285, 211-225.
40. ISHIGE, N., PITTS, L., BERRY, J., et al. (1987). The effects of hypoxia on traumatic head injury in rats: alterations in neurologic function, brain edema, and cerebral blood flow. J. Cereb. Blood Flow Metab. 7, 750-767.
41. IZQUIERDO, I. (1989). Different forms of post-training memory processing. Behav. Neural. Biol. 51, 171-202.
42. JENKINS, L.W., LYETH, B.G., LEWELT, W., et al. (1988). Combined pretrauma scopolamine and phencyclidine attenuate posttraumatic increased sensitivity to delayed secondary ischemia. J. Neurotrauma 5, 275-287.
43. JENKINS, L.W., MOSZYNSKI, K., LYETH, B.G., et al. (1989). Increased vulnerability of the mildly traumatized rat brain to cerebral ischemia: The use of controlled secondary ischemia as a research tool to identify common or different mechanisms contributing to mechanical and ischemic brain injury. Brain. Res. 477, 211.
44. 3H](+)-3-PPP-labeled σ binding sites in guinea pig brain membranes. Eur. J. Pharmacol. 176, 247-148.
45. KATAYAMA, Y., CHEUNG, M.K., GORMAN, L., TAMURA, T., and BECKER, D.L. (1988). Increase in extracellular glutamate and associated massive ionic fluxes following concussive brain injury. Soc. Neurosci. Abstr. 14, 1154.
46. KATAYAMA, Y., BECKER, D.P., TAMURA, T., and HOVDA, D.A. (1990). Massive increases in extracellular potassium and the indiscriminate release of glutamate following concussive brain injury. J. Neurosurg. 73, 889-900.
47. KIMELBERG, H.K. and RANSOM, B.R. (1986). Physiological and pathological aspects of astrocytic swelling in: Astrocytes, Vol. 3. S. Federoff, A. Vernadakis (eds.), Orlando, FL: Academic Press, pps. 129-166.
48. KOCHHAR, A., ZIVIN, J., LYDEN, P., and MAZZARELLA, V. (1988). Glutamate antagonist therapy reduces neurologic deficits produced by focal central nervous system ischemia. Arch. Neurol. 45, 148-153.
49. KOENIG, H., TROUT, J.J., GOLDSTONE, A.D., and LU, C.Y. (1992). Capillary NMDA receptors regulate blood-brain barrier function and breakdown. Brain. Res. 588, 297-303.
50. 2+. Neurosci. Lett. 122, 210-212.
51. KUFFLER, S.W., NICHOLLS, J.G., and MARTIN, A.R. (1984). Physiology of neuroglial cells. in From Neuron to Brain. Sunderland, MA: Sinauer, pps. 323-360.
52. LEGENDRE, P. and WESTBROOK, G. (1991). Ifenprodil blocks N-methyl-D-aspartate receptors by a two-component mechanism. Mol. Pharmacol. 40, 289-298.
53. LEVIN, H.S. (1985). Outcome after head injury. Part II. Neurobehavioral recovery, in Status Report on Central Nervous System Trauma Research. Bethesda: National Institute of Neurological and Communicative Disease and Stroke, pp. 281-299.
54. LOWENSTEIN, D.H., THOMAS, M.J., SMITH, D.H., and MCINTOSH, T.K. (1992). Selective vulnerability of dentate hilar neurons following traumatic brain injury: A potential mechanistic link between head trauma and disorders of the hippocampus. J. Neurosci. 12, 4846-4853.
55. LYETH, B.G., JENKINS, L.W., HAMM, R.J., et al. (1990). Prolonged memory impairment in the absence of hippocampal cell death following traumatic brain injury in the rat. Brain. Res. 526, 249-258.
56. MAEDA, Y. and FURUKAWA, T. (1975). Pharmacological studies on ifenprodil. Folia. Pharmacol. Japonica 71, 585-595.
57. MCGAUGH, J.L. (1989). Involvement of hormonal and neuro-modulatory systems in the regulation of memory storage. Annu. Rev. Neurosci. 12, 255-287.
58. MCINTOSH, T.K., VINK, R., NOBLE, L., YAMAKAMI, I., FERNYAK, S., and FADEN, A.I. (1989a). Traumatic brain injury in the rat: Characterization of a lateral fluid percussion model. Neuroscience 28, 233-244.
59. MCINTOSH, T.K., VINK, R., SOARES, H.D., HAYES, R.L., and SIMON, R. (1989b). Effect of N-methyl-D-aspartate receptor blocker MK-801 on neurological function after experimental brain injury. J. Neurotrauma 6, 247-259.
60. MCINTOSH, T.K., VINK, R., SOARES, H.D., HAYES, R.L., and SIMON, R. (1990). Effects of non-competitive blockade of N-methyl-D-aspartate receptors on the neurochemical sequelae of experimental brain injury. J. Neurochem. 55, 1170-1179.
61. MCINTOSH, T.K. (1994). The neurochemical sequelae of traumatic brain injury: Therapeutic implications. Cerebrovasc. Brain. Metab. Rev. 6, 109-162.
62. MCINTOSH, T.K., OKIYAMA, K., WHITE, W.F., et al. (1995). The NMDA antagonist CP-101,606 improves posttraumatic cognitive function following lateral fluid-percussion brain injury in the rat. J. Neurotrauma 12, 977.
63. MELDRUM, B. (1985). Possible therapeutic applications of antagonists of excitatory amino acid transmitters. Clin. Sci. 68, 113-122.
64. MELDRUM, B.S. (1988). What are the future prospects for agents decreasing excitatory neurotransmission as anti-epileptic agents? in: Frontiers in Excitatory Amino Acid Research. E. Cavalhiero, J. Lehmann, and L. Turski (eds.), New York: A.R. Liss, pp. 195-202.
65. MENNITI, F.S., COLLINS, M.A., CHENARD, B.L., SHALABY, I.A., and WHITE, W.F. (1995). CP-101,606, a potent and selective antagonist of forebrain NMDA receptors: in vitro neuroprotective activity. Soc. Neurosci. Abstr. 21, 72.
66. MEYER, F.B., ANDERSON, R.E., and FRIEDRICH, P.F. (1990). MK-801 attenuates capillary bed compression and hypoperfusion following incomplete focal cerebral ischemial J. Cereb. Blood Flow Metab. 10, 895-902.
67. MILLER, L.P., LYETH, B.G., JENKINS, L.W., et al. (1990). Excitatory amino acid receptor subtype binding following traumatic brain injury. Brain Res. 526, 103-107.
68. MIYAZAKI, S., KATAYAMA, Y., LYETH, B.G., et al. (1992). Enduring suppression of hippocampal long-term potentiation following traumatic brain injury in rat. Brain. Res. 585, 335-339.
69. 3H-glutamate binding sites in rat brain as determined by quantitative autoradiography. J. Neurosci. 5, 2909-2919.
70. MORRIS, R.G.M., ANDERSON, E., LYNCH, G.S., and BAUDRY, M. (1986). Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist. Nature 319, 774-776.
71. MRSULIGA, B.B., STANIMIROVIC, D., MICIC, D.V., and SPATZ, M. (1990). Excitatory amino acid receptors, oxido-reductive processes, and brain oedema following transient ischaemia in gerbils. Acta. Neurochir. (Suppl.) 51, 180-182.
72. NILSSON, P., HILLERED, L., PONTEN, U., and URGERSTEDT, V. (1990). Changes in cortical extracellular levels of energy-related metabolites and amino acids following concussive brain injury in rats. J. Cereb. Blood Flow Metab. 10, 631-637.
73. OKIYAMA, K., SMITH, D.H., THOMAS, M.J., and MCINTOSH, T.K. (1992). Evaluation of a novel calcium channel blocker, (s)-emopamil, on regional cerebral edema and neurobehavioral function after experimental brain injury. J. Neurosurg. 77, 607-615.
74. OKIYAMA, K., SMITH, D.H., GENNARELLI, T.A., SIMON, R.P., LEACH, M., and MCINTOSH, T.K. (1995). The sodium channel blocker and glutamate release inhibitor BW1003C87 and magnesium attenuate regional cerebral edema following experimental brain injury in the rat. J. Neurochem. 64(2), 802-809.
75. OLTON, D.S., BECKER, J.T., and HANDELMANN, G.E. (1979). Hippocampus, space and memory. Behav. Brain. Sci. 2, 316-365.
76. OTOMO, E., ATARASHI, J., ARAKI, G., et al. (1985). Comparison of vinpocetine with ifenprodil tartrate and dihydroergotoxine methylate treatment and results of long-term treatment with vinpocetine. Curr. Ther. Res. 37, 811-821.
77. PALMER, A.M., MARION, D.W., BOTSCHELLER, M.L., SWEDLOW, P.E., STYREN, S.D., and DEKOSKY, S.T. (1993). Traumatic brain injury-induced excitotoxicity assessed in a controlled cortical impact model. J. Neurochem. 61, 2015-2024.
78. PIERCE, J.E.S., SMITH, D.H., EISON, M.S., and MCINTOSH, T.K. (1993). The nootropic compound BMY-21502 improves spatial learning ability in brain-injured rats. Brain. Res. 624, 199-208.
79. REEVES, T.M., LYETH, B.G., and POVLISHOCK, J.T. (1995). Long-term potentiation deficits and excitability changes following traumatic brain injury. Exp. Brain. Res. 106, 248-256.
80. REYNOLDS, I.J. and MILLER, R.J. (1989). Ifenprodil is a novel type of N-methyl-D-aspartate receptor antagonist: interaction with polymines. Mol. Pharmacol. 36, 758-765.
81. ROGERS, B.C., and TILSON, H.A. (1989). MK-801 prevents cognitive and behavioral deficits produced by NMDA receptor overstimulation in the rat hippocampus. Toxicol. Appl. Pharmacol. 99, 445-453.
82. ROTHMAN, S.M. and OLNEY, J.W. (1986). Glutamate and the pathophysiology of hypoxic-ischemic brain damage. Ann. Neurol. 19, 105-111.
83. SHALABY, I.A., PROCHNIAK, M., and CHENARD, B. (1990). Neuroprotective effects of ifenprodil against glutamate toxicity in hippocampal cell cultures. Soc. Neurosci. Abstr. 16, 193.
84. SHAPIRA, Y., YADID, G., COTEV, S., NISKA, A., and SHOHAMI, E. (1990). Protective effect of MK-801 in experimental brain injury. J. Neurotrauma 7, 131-139.
85. SHOHAMI, E., NOVIKOV, M., and BASS, R. (1995). Long-term effect of HU-211, a novel non-competitive NMDA antagonist, on motor and memory functions after closed head injury in the rat. Brain Res. 674, 55-62.
86. SIESJÖ, B.K. (1981). Cell damage to the brain: a speculative hypothesis. J. Cereb. Blood Flow Metab. 1, 155-185.
87. SIMON, R., SWAN, J.H., GRIFFITHS, T., and MELDRUM, B. (1984). Blockade of the N-methyl-D-aspartate receptors may protect against ischemic damage in the brain. Science 226, 850-852.
88. SMITH, D.H., OKIYAMA, K., THOMAS, M.J., CLAUSSEN, B., and MCINTOSH, T.K. (1991). Evaluation of memory dysfunction following experimental brain injury using the Morris Water Maze. J. Neurotrauma 8, 259-269.
89. SMITH, D.H., OKIYAMA, K., GENNARELLI, T.A., and MCINTOSH, T.K. (1993a). Magnesium and ketamine attenuate cognitive dysfunction following experimental brain injury. Neurosci. Lett. 157, 211-214.
90. SMITH, D.H., OKIYAMA, K. THOMAS, M.J., and MCINTOSH, T.K. (1993b). Effects of the excitatory amino acid receptor antagonists kynurenate and indole-2-carboxylic acid on behavioral and neurochemical outcome following experimental brain injury. J. Neurosci. 13, 5383-5392.
91. SMITH, D.H., LOWENSTEIN, D.H., GENNARELLI, T.A., and MCINTOSH, T.K. (1994). Persistent memory dysfunction is associated with bilateral hippocampal damage following experimental brain injury. Neurosci. Lett. 168, 151-154.
92. SOARES, H.D., THOMAS, M., CLOHERTY, K., and MCINTOSH, T.K. (1992a). Development of prolonged focal cerebral edema and regional cation change following experimental brain injury in the rat. J. Neurochem. 58, 1845-1852.
93. SOARES, H.D., THOMAS, M.J., CLOHERTY, K., and MCINTOSH, T.K. (1992b). Development of prolonged focal cerebral edema and regional cation change following experimental brain injury in the rat. J. Neurochem. 58, 1845-1852.
94. SOARES, H.D., HICKS, R.R., SMITH, D.H., and MCINTOSH, T.K. (1995). Inflammatory leukocytic recruitment and diffuse neuronal degeneration are separate pathological processes resulting from traumatic brain injury. J. Neurosci. 15, 8223-8233.
95. SQUIRE, L.R. (1996). Memory and Brain. Oxford University Press: New York.
96. STEINBERG, G.K., SALEH, J., DELAPAZ, R., KUNIS, D., and ZARNEGAR, S.R. (1989a). Pretreatment with NMDA antagonist dextrorphan reduces cerebral injury following transient focal ischemia in rabbits. Brain Res. 497, 382-386.
97. STEINBERG, G.K., SALEH, J., KUNIS, D., DELAPAZ, R., and ZARNEGAR, S.R. (1989b). Protective effect of N-methyl-D-aspartate antagonists after focal ischemia in rabbits. Stroke 20, 1247-1252.
98. SUTTON, R.L. and FEENEY, D.M. (1992). α-noradrenergic agonists and antagonists affect recovery and maintenance of beam-walking ability after sensorimotor cortex ablation in the rat. Restorat. Neurol. Neurosci. 4, 1-11.
99. SUTTON, R.L., SUTHERLAND, R.J., QUINTANA, G., GUTIERREZ, T., and FEENEY, D.M. (1992). Spatial learning deficits in rats with cortical contusion injury. Soc. Neurosci. Abstr. 18, 170.
100. TOULMOND, S., VIGE, X., GAGE, C., and BENAVIDES, J. (1992). Local infusion of interleukin-6 attenuates the neurotoxic effects of NMDA on rat striatal cholinergic neurons. Neurosci. Lett. 144, 49-52.
101. WHITE, W.F., DUCAT, M.F., CHENARD, B.L., BUTLER, T.W., and RONAU, R.T. (1995). CP-101,606, a potent and selective antagonist of forebrain NMDA receptors: binding to a novel recognition site. Soc. Neurosci. Abstr. 21, 1114.
102. WIELOCH, T. (1985). Hypoglycemia-induced neuronal damage prevented by an N-methyl-D-aspartate antagonist. Science 230, 681-683.
103. YOUNG, A.R., BOULOY, M., BOPUSSARD, J.-F., EDVINSSON, K., and MACKENZIE, E.T. (1981). Direct vascular effects of agents used in the pharmacotherapy of cerebrovascular disease on isolated cerebral vessels. J. Cereb. Blood Flow Metab. 1, 117-128.
104. ZAUNER, A. and BULLOCK, R. (1995). The role of excitatory amino acids in severe brain trauma: opportunities for therapy: a review. J. Neurotrauma 12, 547-554.
105. ZEEVALK, G.D. and NIKLAS, W.J. (1990). Action of the anti-ischemic agent ifenprodil on N-methyl-D-aspartate and kainate-mediated excitotoxicity. Brain. Res. 522, 135-139.