Skip to main content
SpringerLink
Log in

Excitatory Amino Acids and Neuroprotection

  • Chapter
  • First Online:
Emerging Strategies in Neuroprotection

Part of the book series: Advances in Neuroprotection ((AN,volume 22))

Abstract

This chapter reviews approaches to neuroprotection that are based on reducing the excitotoxic effects of glutamate and related compounds. Evidence for a role of excitotoxicity in the brain damage that accompanies cerebral ischemia and trauma has been presented elsewhere (Choi and Rothman, 1990; Meldrum, 1990; Meldrum and Garthwaite, 1990; Olney, 1990) and will not be further reviewed here. Nor shall we provide any review or analysis of the different animal models of cerebral ischemia and trauma in which putative cerebroprotective agents are currently evaluated [these aspects are reviewed by Meldrum, 1990, and in Chapters 3 (Hsu et al.), 4 (Zivin), and 5 (Hayes et al.) of this volume]. Here we shall consider the various pharmacologic options for reducing excitatory effects, reviewing the drugs available for modifying the different stages of the excitotoxic process and the evidence for their cerebroprotective efficacy in animal models.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adamson P, Hajimohammadreza I, Brammer MJ, Campbell I, Meldrum BS (1990): Presynaptic glutamate/quisqualate receptors: Effects on synaptosomal free calcium concentrations. J Neurochem 55: 1850–1854

    Article  CAS  PubMed  Google Scholar 

  • Andine P, Lehmann A, Ellren K, Wennberg E, Kjellmer I, Nielsen T, Hagberg H (1988): The excitatory amino acid antagonist kynurenic acid administered after hypoxia-ischemia in neonatal rats offers neuroprotection. Neurosci Lett 90: 208–212

    Article  CAS  PubMed  Google Scholar 

  • Arai A, Kessler M, Lee K, Lynch G (1990): Calpain inhibitors improve the recovery of synaptic transmission from hypoxia in hippocampal slices. Brain Res 532: 63–68

    Article  CAS  PubMed  Google Scholar 

  • Arvin B, Le Peillet E, Dürmüller N, Chapman AG, Meldrum BS (1992): Electrolytic lesions of the locus coeruleus, or 6-hydroxy dopamine lesions of the medial forebrain bundle protect against excitotoxic damage in rat hippocampus. Brain Res (in press)

    Google Scholar 

  • Aston-Jones G, Akaoka H, Charléty P, Chouvet G (1991): Serotonin selectively attenuates glutamate-evoked activation of noradrenergic locus coeruleus neurons. J Neurosci 11: 760–769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beaughard M, Michelin MT, Massingham R (1990): Effects of the putative glycine antagonist HA-966 on the neurological and histological changes induced by transient global cerebral ischemia in rats and gerbils. In: Pharmacology of Cerebral Ischemia 1990, Krieglstein J, Oberpichler H, eds. Stuttgart: Wissenschaftliche Verlagsgesellschaft, p 275

    Google Scholar 

  • Bielenberg GW, Burkhardt M (1990): 5-HT1A agonists show neuroprotectant activity in rats and mice. Eur J Pharmacol 183: 1953–1954

    Article  Google Scholar 

  • Block GA, Pulsinelli WA (1988): Excitatory amino acid and purinergic transmitter involvement in ischemia-induced selective neuronal death. In: Mechanisms of Cerebral Hypoxia and Stroke, Somjen G, ed. New York: Plenum Press, p 359

    Chapter  Google Scholar 

  • Boast CA, Gerhardt SC, Janak P (1987): Systemic AP7 reduces ischemic brain damage in gerbils. In: Excitatory Amino Acid Transmission, Hicks TP, Lodge D, McLennan H, eds. New York: Alan R. Liss, p 249

    Google Scholar 

  • Boast CA, Gerhardt SC, Pastor G, Lehmann J, Etienne PE, Liebman JM (1988): The N-methyl-n-aspartate antagonists CGS 19755 and CPP reduce ischemic brain damage in gerbils. Brain Res 442: 345–348

    Article  CAS  PubMed  Google Scholar 

  • Bode-Greuel KM, Klisch J, Glaser T, Traber J (1990): Serotonin (5-HT) lA receptor agonists as neuroprotective agents in cerebral ischemia. In: Pharmacology of Cerebral Ischemia 1990, Krieglstein J, Oberpichler H, eds. Stuttgart: Wissenschaftliche Verlagsgesellschaft, p 485

    Google Scholar 

  • Boulter J, Hollmann M, O’Shea-Greenfield A, Hartley M, Deneris E, Maron C, Heinemann S (1990): Molecular cloning and functional expression of glutamate receptor subunit genes. Science 249: 1033–1037

    Article  ADS  CAS  PubMed  Google Scholar 

  • Buchan A, Pulsinelli WA (1990): Hypothermia but not the N-methyl-D-aspartate antagonist, MK-801, attenuates neuronal damage in gerbils subjected to transient global ischemia. J Neurosci 10: 311–316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Buchan AM, Li H, Pulsinelli WA (1991): The N-methyl-n-aspartate antagonist, MK-801, fails to protect against neuronal damage caused by transient severe forebrain ischemia in adult rats. J Neurosci 11: 1049–1056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Buchan AM, Xue D, Slivka A (1990): MK-801 reduces the volume of neocortical infarction but also increases regional cerebral blood flow. Stroke 21, 163

    Google Scholar 

  • Bullock R, Graham DI, Chen M-H, Lowe D, McCulloch J (1990): Focal cerebral ischemia in the cat: Pretreatment with a competitive NMDA receptor antagonist, D-CPPene. J Cereb Blood Flow Metab 10: 668–674

    Article  CAS  PubMed  Google Scholar 

  • Carter C, Benavides J, Legendre P, Vincent JD, Noel F, Thuret F, Lloyd KG, Arbilla S, Zivkovic B, MacKenzie ET, Scatton B, Langer SZ (1988): Ifenprodil and SL 82.0715 as cerebral anti-ischemic agents. II. Evidence for N-methyl-Daspartate receptor antagonist properties. J Pharmacol Exp Ther 247: 1222–1232

    CAS  PubMed  Google Scholar 

  • Carter CJ, Lloyd KG, Zivkovic B, Scatton B (1990): Ifenprodil and SL 82.0715 as cerebral antiischemic 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

    CAS  PubMed  Google Scholar 

  • Chapman AG, Dürmüller N, Lees GJ, Meldrum BS (1989): Excitotoxicity of NMDA and kainic acid is modulated by nigrostriatal dopaminergic fibres. Neurosci Lett 107: 256–260

    Article  CAS  PubMed  Google Scholar 

  • Chapman AG, Meldrum BS (1989): Non-competitive N-methyl-n-aspartate antagonists protect against sound-induced seizures in DBA/2 mice. Eur J Pharmacol 166: 201–211

    Article  CAS  PubMed  Google Scholar 

  • Choi DW (1990): Cerebral hypoxia: Some new approaches and unanswered questions. J Neurosci 10: 2493–2501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Choi DW, Rothman SM (1990): The role of glutamate neurotoxicity in hypoxicischemic neuronal death. Annu Rev Neurosci 13: 171–182

    Article  CAS  PubMed  Google Scholar 

  • Diemer NH, Johansen FF, Jorgensen MB (1990): N-Methyl-D-aspartate and nonN-methyl-D-aspartate antagonists in global cerebral ischemia. Stroke 21 (Suppl 3):III39–III42

    Google Scholar 

  • Duverger D, McKenzie ET (1988): The quantification of cerebral infarction following focal ischemia in the rat: Influence of strain, arterial pressure, blood glucose concentration, and age. J Cereb Blood Flow Metab 8: 449–461

    Article  CAS  PubMed  Google Scholar 

  • Eaton SA, Salt TE (1989): Modulatory effects of serotonin on excitatory amino acid responses and sensory synaptic transmission in the ventrobasal thalamus. Neuroscience 33: 285–292

    Article  CAS  PubMed  Google Scholar 

  • Egebjerg J, Bettler B, Hermans-Borgmeyer I, Heinemann S (1991): Cloning of a cDNA for a glutamate receptor subunit activated by kainate but not AMPA. Nature 351: 745–748

    Article  ADS  CAS  PubMed  Google Scholar 

  • Faden AI, Demediuk P, Panter SS, Vink R (1989): The role of excitatory amino acids and NMDA receptors in traumatic brain injury. Science 244: 798–800

    Article  ADS  CAS  PubMed  Google Scholar 

  • Faden AI, Simon RP (1988): A potential role for excitotoxins in the pathophys-iology of spinal cord injury. Ann Neurol 23: 623–626

    Article  CAS  PubMed  Google Scholar 

  • Favaron M, Manev H, Siman R (1990): Down regulation of protein kinase C protects cerebellar granule neurons in primary culture from glutamate-induced neuronal death. Proc Natl Acad Sci USA 87: 1983–1987

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Fleischer JE, Tateishi A, Drummond JC, Scheller MS, Grafe MR, Zornow MH, Shearman GT, Shapiro HM (1989): MK-801, an excitatory amino acid antagonist, does not improve neurologic outcome following cardiac arrest in cats. J Cereb Blood Flow Metab 9: 795–804

    Article  CAS  PubMed  Google Scholar 

  • Forsythe ID, Clements JD (1990): Presynaptic glutamate receptors depress excitatory monosynaptic transmission between mouse hippocampal neurones. JPhysiol (London) 429: 1–16

    Article  CAS  Google Scholar 

  • Foster AC (1991): Channel blocking drugs for the NMDA receptor. In: Excitatory Amino Acid Antagonists, Meldrum BS, ed. Oxford: Blackwell Scientific Publications, p 164

    Google Scholar 

  • Frandsen A, Schousboe A (1991): Dantrolene prevents glutamate cytotoxicity and Ca2+ release from intracellular stores in cultured cerebral cortical neurons. J Neurochem 56: 1075–1078

    Article  CAS  PubMed  Google Scholar 

  • Gannon RL, Baty LT, Terrian DM (1989): L(+)-2-Amino-4-phosphonobutyrate inhibits the release of both glutamate and dynorphin from guinea pig but not rat hippocampal mossy fiber synaptosomes. Brain Res 495: 151–155

    Article  CAS  PubMed  Google Scholar 

  • Germano IM, Pitts LH, Meldrum BS, Bartkowski HM, Simon RP (1987): Kynurenate inhibition of cell excitation decreases stroke size and deficits. Ann Neurol 22: 730–734

    Article  CAS  PubMed  Google Scholar 

  • Gill R, Foster AC, Woodruff GN (1987): Systemic administration of MK-801 protects against ischemia-induced hippocampal neurodegeneration in the gerbil. J Neurosci 7: 3343–3349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gill R, Foster AC, Woodruff GN (1988): MK-801 is neuroprotective in gerbils when administered during the post-ischemic period. Neuroscience 25: 847–856

    Article  CAS  PubMed  Google Scholar 

  • Gill R, Lodge D (1991): The neuroprotective action of 2,3-dihydroxy-6-nitro-7sulfamoyl-benzo(F)quinoxaline (NBQX) in a rat focal ischemia model. Brit J Pharmacol 102: 61 P

    Google Scholar 

  • Globus MYT, Ginsberg MD, Dietrich WD, Busto R, Scheinberg P (1987): Sub-stantia nigra lesion protects against ischemic damage in the striatum. Neurosci Lett 80: 251–256

    Article  CAS  PubMed  Google Scholar 

  • Gotti B, Benavides J, MacKenzie ET, Scatton B (1990): The pharmacotherapy of focal cortical ischemia in the mouse. Brain Res 522: 290–307

    Article  CAS  PubMed  Google Scholar 

  • Gotti B, Duverger D, Bertin J, Carter C, Dupont R, Frost J, Gaudilliere B, MacKenzie ET, Rousseau J, Scatton B, Wick A (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

    CAS  PubMed  Google Scholar 

  • Grotta JC (1987): Current medical and surgical therapy for cerebrovascular disease. N Engl J Med 317: 1505–1516

    Article  CAS  PubMed  Google Scholar 

  • Grotta JC, Picone CM, Ostrow PT, Strong RA, Earls RM, Yao LP, Rhoades HM, Dedman JR (1990): CGS-19755, a competitive NMDA receptor antagonist, reduces calcium-calmodulin binding and improves outcome after global cerebral ischemia. Ann Neurol 27: 612–619

    Article  CAS  PubMed  Google Scholar 

  • Gustafson I, Miyauchi Y, Wieloch TW (1989): Postischemic administration of idazoxan, an a-2 adrenergic receptor antagonist, decreases neuronal damage in the rat brain. J Cereb Blood Flow Metab 9: 171–174

    Article  CAS  PubMed  Google Scholar 

  • Hagberg H, Andine P, Fredholm B, Rudolphi K (1990): Effect of the adenosine uptake inhibitor propentofylline on extracellular adenosine and glutamate and evaluation of its neuroprotective effect after ischemia in neonatal and adult rats. In: Pharmacology of Cerebral Ischemia 1990, Krieglstein J, Oberpichler H, eds. Stuttgart: Wissenschaftliche Verlagsgesellschaft, p 427

    Google Scholar 

  • Hall ED, Pazara KE (1988): Quantitative analysis of effects of kappa-opioid agonists and post-ischemic hippocampal CA1 neuronal necrosis in gerbils. Stroke 19: 1008–1012

    Article  CAS  PubMed  Google Scholar 

  • Hatfield RH, Mendelow AD, Alvares L (1990): Triphenyltetrazolium chloride (TTC) as a marker of ischemic changes in rat brain after MCA occlusion. J Neurol Neurosurg Psychiatry 53: 446

    Google Scholar 

  • Honoré T, Davies SN, Drejer J, Fletcher EJ, Jacobsen P, Lodge D, Nielsen FE (1988): Quinoxalinediones: Potent competitive non-NMDA glutamate receptor antagonists. Science 241: 701–703

    Article  ADS  PubMed  Google Scholar 

  • Ikonomidou C, Price MT, Mosinger JL, Frierdich G, Labruyere J, Shahid Salles K, Olney JW (1989): Hypobaric-ischemic conditions produce glutamate-like cytopathology in infant rat brain. J Neurosci 9: 1693–1700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Keana JFW, McBurney RN, Scherz MW, Fischer JB, Hamilton PN, Smith SM, Server AC, Finkbeiner S, Stevens CF, Jahr C, Weber E (1989): Synthesis and characterization of a series of diarylguanidines that are noncompetitive N-methylD-aspartate receptor antagonists with neuroprotective properties. Proc Natl Acad Sci USA 86: 5631–5635

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Keinanen K, Wisden W, Sommer B, Werner P, Herb A, Verdoorn TA, Sakmann B, Seeburg PH (1990): A family of AMPA-selective glutamate receptors. Science 249: 556–560

    Article  ADS  CAS  PubMed  Google Scholar 

  • Kirino T, Tamura A, Sano K (1986): A reversible type of neuronal injury following ischemia in the gerbil hippocampus. Stroke 17: 455–459

    Article  CAS  PubMed  Google Scholar 

  • Kuroiwa T, Bonnekoh P, Hossmann K-A (1990): Therapeutic window of CA1 neuronal damage defined by an ultrashort-acting barbiturate after brain ischemia in gerbils. Stroke 21: 1489–1493

    Article  CAS  PubMed  Google Scholar 

  • Lanier WL, Perkins WJ, Karlsson BR, Milde JH, Scheithauer BW, Shearman GT, Michenfelder JD (1990): The effects of dizocilpine maleate (MK-801), an antag-onist of the N-methyl-D-aspartate receptor, on neurologic recovery and histopathology following complete cerebral ischemia in primates. J Cereb Blood Flow Metab 10: 252–261

    Article  CAS  PubMed  Google Scholar 

  • Lee KS, Frank S, Vanderklish P, Arai A, Lynch G (1991): Inhibition of proteolysis protects hippocampal neurons from ischemia. Proc Natl Acad Sci USA 88: 7233–7237

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Leach MJ, Marden CM, Miller AA (1986): Pharmacological studies on lamotrigine, a novel potential antiepileptic drug. II. Neurochemical studies on the mechanism of action. Epilepsia 27: 490–497

    Article  CAS  PubMed  Google Scholar 

  • Le Peillet E, Arvin B, Moncada C, Meldrum BS (1992): The non-NMDA antagonists, NBQX and GYKI 52466, protect against cortical and striatal cell loss following transient global ischaemia in the rat. Brain Res 571: 115–120

    Article  PubMed  Google Scholar 

  • Lester RA, Jahr CE (1990): Quisqualate receptor-mediated depression of calcium currents in hippocampal neurons. Neuron 4: 741–749

    Article  CAS  PubMed  Google Scholar 

  • Levine S (1960): Anoxic-ischemic encephalopathy in rats. Am J Pathol 36: 1–17

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liman ER, Knapp AG, Dowling JE (1989): Enhancement of kainate-gated currents in retinal horizontal cells by cyclic AMP-dependent protein kinase. Brain Res 481: 399–402

    Article  CAS  PubMed  Google Scholar 

  • Lin B, Dietrich WD, Busto R, Ginsberg MD (1990): (s)-Emopamil protects against global ischemic brain injury in rats. Stroke 21: 1734–1739

    Article  CAS  PubMed  Google Scholar 

  • Madden KP, Clark WM, Kochhar A, Zivin JA (1991): Effect of protein kinase C modulation on outcome of experimental CNS ischemia. Brain Res 547: 193–198

    Article  CAS  PubMed  Google Scholar 

  • Malenka RC, Madison DV, Nicoll RA (1986): Potentiation of synaptic transmission in the hippocampus by phorbol esters. Nature 321: 175–177

    Article  ADS  CAS  PubMed  Google Scholar 

  • Manev H, Favaron M, Vicini S, Guidotti A, Costa E (1990): Glutamate-induced neuronal death in primary cultures of cerebellar granule cells: Protection by synthetic derivatives of endogenous sphingolipids. J Pharmacol Exp Ther 252: 419–427

    CAS  PubMed  Google Scholar 

  • Marchi M, Bocchieri P, Garbarino L, Raiteri M (1989): Muscarinic inhibition of endogenous glutamate release from rat hippocampus synaptosomes. Neurosci Lett 96: 229–234

    Article  CAS  PubMed  Google Scholar 

  • Markwell MAK, Berger SP, Paul SM (1990): The polyamine synthesis inhibitor a-difluoromethylornithine blocks NMDA-induced neurotoxicity. Eur J Pharmacol 182: 607–609

    Article  CAS  PubMed  Google Scholar 

  • Martin D, Bustos GA, Bowe MA, Bray SD, Nadler JV (1991): Autoreceptor regulation of glutamate and aspartate release from slices of the hippocampal CA1 area. J Neurochem 56: 1647–1655

    Article  CAS  PubMed  Google Scholar 

  • Masu M, Tanabe Y, Tsuchida K, Shigemoto R, Nakanishi S (1991): Sequence and expression of a metabotropic glutamate receptor. Nature 349: 760–765

    Article  ADS  CAS  PubMed  Google Scholar 

  • Mayer ML (1991): Physiology and biophysics of the NMDA receptor channel complex. In: Excitatory Amino Acid Antagonists, Meldrum BS, ed, p. 64. Blackwell Scientific Publications, Oxford

    Google Scholar 

  • McDonald JW, Silverstein FS, Johnston MV (1987): MK-801 protects the neonatal brain from hypoxic-ischemic damage. Eur J Pharmacol 140: 359–361

    Article  CAS  PubMed  Google Scholar 

  • Meldrum BS (1990): Protection against ischemic neuronal damage by drugs acting on excitatory neurotransmission. Cerebrovasc Brain Metab Rev 2: 27–57

    CAS  PubMed  Google Scholar 

  • Meldrum BS, ed (1991): Excitatory Amino Acid Antagonists Oxford: Blackwell Scientific Publications

    Google Scholar 

  • Meldrum BS, Garthwaite J (1990): Excitatory amino acid neurotoxicity and neurodegenerative disease. Trends Pharmacol Sci 11: 379–387

    Article  CAS  PubMed  Google Scholar 

  • Meldrum BS, Swan JH, Leach MJ, Millan MH, Gwinn R, Kadota K, Graham SH, Chen J, Simon RP (1992): Reduction of glutamate release and protection against ischemic brain damage by BW 1003C87. Brain Res (in press)

    Google Scholar 

  • Meldrum BS, Swan JH, Millan MH, Leach MJ, Gwinn R, Kadota K, Graham SH, Simon RP (1991): A pyrimidine derivative, BW 1003C87, decreases glutamate release and protects against ischemic damage. In: The Role of Neurotransmitters in Brain Injury, Dietrich WD, Globus M Y-T, eds. New York: Plenum Publishing Corporation (in press)

    Google Scholar 

  • Michenfelder JD, Lanier WL, Scheithauer BW, Perkins WJ, Shearman GT, Milde JH (1989): Evaluation of the glutamate antagonist dizocilipine maleate (MK-801) on neurologic outcome in a canine model of complete cerebral ischemia: correlation with hippocampal histopathology. Brain Res 481: 228–234

    Article  CAS  PubMed  Google Scholar 

  • Miyamoto M, Coyle JT (1990): Idebenone attenuates neuronal degeneration induced by intrastriatal injection of excitotoxins. Exp Neurol 108, 38–45

    Article  CAS  PubMed  Google Scholar 

  • Miyamoto M, Murphy TH, Sartre A, Schnaar RL, Coyle JT (1989): Antioxidants protect against glutamate-induced cytotoxicity in a neuronal cell line. J Pharmacol Exp Ther 250: 1132–1140

    CAS  PubMed  Google Scholar 

  • Moriyoshi K, Masu M, Ishii T, Shigemoto R, Mizuno N, Nakanishi S (1991): Molecular cloning and characterization of the rat NMDA receptor. Nature 354: 31–37

    Article  ADS  CAS  PubMed  Google Scholar 

  • Mouradian RD, Sessler FM, Waterhouse BD (1991): Noradrenergic potentiation of excitatory transmitter action in cerebrocortical slices: Evidence for mediation by an alpha, receptor-linked second messenger pathway. Brain Res 546: 83–95

    Article  CAS  PubMed  Google Scholar 

  • Mulder AH, Burger DM, Wardeh G, Hogenboom F, Frankhuyzen AL (1991): Pharmacological profile of various kappa-agonists at kappa-, mu-and deltaopioid receptors mediating presynaptic inhibition of neurotransmitter release in the rat brain. Br J Pharmacol 102: 518–522

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nicholls D, Attwell D (1990): The release and uptake of excitatory amino acids. Trends Pharmacol Sci 11: 462–467

    Article  PubMed  Google Scholar 

  • Nichols RA, Sihra TS, Czernik AJ, Nairn AC, Greengard P (1990): Calcium/ calmodulin-dependent protein kinase II increases glutamate and noradrenaline release from synaptosomes. Nature 343: 647–651

    Article  ADS  CAS  PubMed  Google Scholar 

  • Nuglisch J, Karkoutly C, Peruche B, Prehn JHM, Welsch M, Mennel HD, Rossberg C, Krieglstein J (1990): Effect of the 5-HT 1A-agonist CM57493 on infarct area, infarct volume and hippocampal neuronal damage after focal and global cerebral ischemia in mice and in rats. In: Pharmacology of Cerebral Ischemia 1990, Krieglstein J, Oberpichler H, eds. Stuttgart: Wissenschaftliche Verlagsgesellschaft, p 493

    Google Scholar 

  • Olney JW (1990): Excitotoxic amino acids and neuropsychiatric disorders. Annu Rev Pharmacol Toxicol 30: 47–71

    Article  CAS  PubMed  Google Scholar 

  • Olney JW, Ikonomidou C, Mosinger JL, Friedrich G (1989): MK-801 prevents hypobaric-ischemic neuronal degeneration in infant rat brain. J Neurosci 9: 1701–1704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ouardouz M, Durand J (1991): GYKI 52466 antagonizes glutamate responses but not NMDA and kainate responses in rat abducens motoneurones. Neurosci Lett 125: 5–8

    Article  CAS  PubMed  Google Scholar 

  • Ozyurt E, Graham DI, Woodruff GN, McCulloch J (1988): Protective effect of the glutamate antagonist, MK-801 in focal cerebral ischemia in the cat. J Cereb Blood Flow Metab 8: 138–143

    Article  CAS  PubMed  Google Scholar 

  • Palfreyman MG, Baron BM (1991): Non-competitive NMDA antagonists acting on the glycine site. In: Excitatory Amino Acid Antagonists, Meldrum BS, ed. Oxford: Blackwell Scientific Publications, p 101

    Google Scholar 

  • Park CK, Nehls DG, Graham DI, Teasdale GM, McCulloch J (1988a): The glutamate antagonist MK-801 reduces focal ischemic damage in the rat. Ann Neurol24, 543–551

    Google Scholar 

  • Park CK, Nehls DG, Graham DI, Teasdale GM, McCulloch J (1988b): Focal cerebral ischemia in the cat: treatment with the glutamate antagonist MK-801 after induction of ischemia. J Cereb Blood Flow Metab 8: 757–762

    Article  CAS  PubMed  Google Scholar 

  • Paschen W, Rohn G, Meese CO, Pjunicie B, Schmidt-Kastner R (1991): Polyamine metabolism in reversible cerebral ischemia: Effects of a-difluoromethylornithine. Brain Res 453: 9–16

    Article  Google Scholar 

  • Pellegrini-Giampietro DE, Cherici G, Alesiani M, Carla V, Moroni F (1990): Excitatory amino acid release and free radical formation may cooperate in the genesis of ischemia-induced neuronal damage. J Neurosci 10: 1035–1041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Phillis JW, Walter GA, Simpson RE (1991): Brain adenosine and transmitter amino acid release from the ischemic rat cerebral cortex: Effects of the adenosine deaminase inhibitor deoxycoformycin. J Neurochem 56: 644–650

    Article  CAS  PubMed  Google Scholar 

  • Prince DA, Feeser HR (1988): Dextromethorphan protects against cerebral infarc-tion in a rat model of hypoxia-ischemia. Neurosci Lett 85: 291–296

    Article  CAS  PubMed  Google Scholar 

  • Rice JE, Vannucci RC, Brierley JB (1981): The influence of immaturity on hypoxic-ischemic brain damage in the rat. Ann Neurol 9: 131–141

    Article  PubMed  Google Scholar 

  • Rod MR, Auer RN (1989): Pre-and post-ischemic administration of dizocilpine (MK-801) reduces cerebral necrosis in the rat. Can J Neurol Sci 16: 340–344

    Article  CAS  PubMed  Google Scholar 

  • Roman R, Bartkowski H, Simon R (1989): The specific NMDA receptor antagonist AP-7 attenuates focal ischemic brain injury. Neurosci Lett 104: 19–24

    Article  CAS  PubMed  Google Scholar 

  • Seren MS, Rubini R, Lazzaro A, Zanoni R, Fiori MG, Leon A (1990): Protective effects of a monosialoganglioside derivative following transitory forebrain ischemia in rats. Stroke 21: 1607–1612

    Article  CAS  PubMed  Google Scholar 

  • Seubert P, Lee K, Lynch G (1989): Ischemia triggers NMDA receptor-linked cytoskeletal proteolysis in hippocampus. Brain Res 492: 366–370

    Article  CAS  PubMed  Google Scholar 

  • Sheardown MJ, Nielsen EO, Hansen AJ, Jacobsen P, Honoré T (1990): 2,3Dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline: A neuroprotectant for cerebral ischemia. Science 247: 571–574

    Article  ADS  CAS  PubMed  Google Scholar 

  • Silvia RC, Slizgi GR, Ludens JH, Tang AH (1987): Protection from ischemia-induced cerebral edema in the rat by U-50488H, a kappa opioid receptor agonist. Brain Res 403: 52–57

    Article  CAS  PubMed  Google Scholar 

  • Siman R (1990): Role of calpain I in excitatory amino acid-induced degenerative structural changes. In: Neurotoxicity of Excitatory Amino Acids, Guidotti A, ed. New York: Raven Press, p 145

    Google Scholar 

  • Siman R, Noszek JC, Kegerise C (1989): Calpain I activation is specifically related to excitatory amino acid induction of hippocampal damage. J Neurosci 9: 1579–1590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simmonds MA, Horne AL (1988): Barbiturates and excitatory amino acid interactions. In: Excitatory Amino Acids in Health and Disease, Lodge D, ed. Chichester: John Wiley & Sons, p 219

    Google Scholar 

  • Swan JH, Evans MC, Meldrum BS (1988): Long-term development of selective neuronal loss and the mechanism of protection by 2-amino-7-phosphonoheptanoate in a rat model of incomplete forebrain ischemia. J Cereb Blood Flow Metab 8: 64–78

    Article  CAS  PubMed  Google Scholar 

  • Swan JH, Meldrum BS (1990): Protection by NMDA antagonists against selective cell loss following transient ischemia. J Cereb Blood Flow Metab 10: 343–351

    Article  CAS  PubMed  Google Scholar 

  • Takata Y, Ozawa J, Kato H (1991): A selective effect of protein kinase C activators on noradrenaline release compared with subsequent contraction in canine isolated saphenous veins. Brit J Pharmacol 102: 955–961

    Article  CAS  Google Scholar 

  • Tarnawa I, Engberg I, Flatman JA (1990): GYKI 52466, an inhibitor of spinal reflexes is a potent quiqualate antagonist. In: Amino Acids. Chemistry, Biology, and Medicine, Lubec G, Rosenthal GA, eds. Leiden: Escom, p 538

    Chapter  Google Scholar 

  • Turner JP, Meldrum BS (1991): L-Glutamate diethyl ester and deaminated analogues as excitatory amino acid antagonists in rat cerebral cortex. Brit J Pharmacol 104: 445–451

    Article  CAS  Google Scholar 

  • Warner MA, Nadler JV, Crain BJ (1990): Effects of NMDA receptor antagonists and body temperature in the gerbil carotid occlusion model of transient forebrain ischemia. In: Current and Future Trends in Anticonvulsant Anxiety and Stroke Therapy, Meldrum BS, Williams M, eds. New York: Alan R. Liss

    Google Scholar 

  • Watkins JC (1991): Structure/activity relations of competitive NMDA receptor antagonists. In: Excitatory Amino Acid Antagonists, Meldrum BS, ed. Oxford: Blackwell Scientific Publications, p 84

    Google Scholar 

  • Watkins JC, Evans RH (1981): Excitatory amino acid transmitters. Annu Rev Pharmacol Toxicol 21: 165–204

    Article  CAS  PubMed  Google Scholar 

  • Wong RKS (1990): Intracellular Ca2+: Glutamate-induced elevation and role as a messenger in hippocampal pyramidal cells. In: Neurotoxicity of Excitatory Amino Acids, Guidotti A, ed. New York: Raven Press, p 19

    Google Scholar 

  • Wood PL, Emmett MR, Rao TS, Cler J, Mick S, Iyengar S (1990): Inhibition of nitric oxide synthase blocks N-methyl-D-aspartate-, quisqualate-, kainate-, harmaline-, and pentylenetetrazole-dependent increases in cerebellar cyclic GMP in vivo. J Neurochem 55: 346–348

    Article  CAS  PubMed  Google Scholar 

  • Wroblewski JT, Blaker WD, Meek JL (1985): Ornithine as a precursor of neurotransmitter glutamate: Effect of canaline on ornithine aminotransferase activity and glutamate content in the septum of rat brain. Brain Res 329: 161–168

    Article  CAS  PubMed  Google Scholar 

  • Xiang J-Z, Adamson P, Brammer MJ, Campbell IC (1990): The kappa-opiate agonist U50488H decreases the entry of 45Ca into rat cortical synaptosomes by inhibiting N- but not L-type calcium channels. Neuropharmacology 29: 439–444

    Article  CAS  PubMed  Google Scholar 

  • Xiang J-Z, Brammer MJ, Campbell IC (1991): Quisqualate and carbachol-induced increases in intrasynaptosomal free calcium are mediated by different products of phospholipid hydrolysis. Mol Pharmacol 207: 93–100

    CAS  Google Scholar 

Download references

Authors
  1. Brian Meldrum
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. NeuroTherapeutics Corp. and Center for Neurologic Study, 11211 Sorrento Valley Road, 92121, San Diego, CA, USA

    Paul J. Marangos

  2. Department of Pharmacology, Texas College of Osteopathic Medicine, 3500 Camp Bowie Boulevard, 76107, Fort Worth, TX, USA

    Harbans Lal

Rights and permissions

Reprints and permissions

Copyright information

© 1992 Birkhäuser Boston

About this chapter

Cite this chapter

Meldrum, B. (1992). Excitatory Amino Acids and Neuroprotection. In: Marangos, P.J., Lal, H. (eds) Emerging Strategies in Neuroprotection. Advances in Neuroprotection, vol 22. Birkhäuser, Boston, MA. https://doi.org/10.1007/978-1-4684-6796-3_7

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-6796-3_7

  • Published:

  • Publisher Name: Birkhäuser, Boston, MA

  • Print ISBN: 978-1-4684-6798-7

  • Online ISBN: 978-1-4684-6796-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation