Advertisement

Neurotransmitter Release in Experimental Stroke Models: The Role of Glutamate-Gaba Interaction

  • Laszlo G. HarsingJr.
  • Gabor Gigler
  • Mihaly Albert
  • Gabor Szenasi
  • Annamaria Simo
  • Krisztina Moricz
  • Attila Varga
  • Istvan Ling
  • Erzsebet Bagdy
  • Istvan Kiraly
  • Sandor Solyom
  • Zsolt Juranyi
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 541)

Abstract

Stroke or cerebrovascular accident reduces blood flow and decreases oxygen supply (ischemia) in brain tissue. This may be resulted from vascular obstruction when a blood vessel is blocked or by hemorrhage when bleeding occurs into the brain tissue. Decrease in oxygen supply shifts pH to acidosis and increases extracellular K+ concentration, which depolarizes neural cell membrane. Anoxic depolarization leads to excessive release of glutamate, which then activates various glutamate receptors in the synapse or the extrasynaptic space. Opening of ionotropic glutamate receptors (NMDA, AMPA and kainate receptors) causes influx of Na+ through the activated glutamate-gated ion channels. In response to anoxia, Ca2+ also enters the cells in excessive amounts via activated NMDA receptors and Ca2+-permeable AMPA receptors. This will lead to activation of several Ca2+-dependent intracellular signal transduction pathways (proteases, kinases, endonucleases, lipoxygeneses and nitric oxide synthase), which ultimately leads to neural death (Vizi et al., 1996; Parsons et al., 1998).

Keywords

Middle Cerebral Artery Middle Cerebral Artery Occlusion Glutamate Release Ischemic Insult Gaba Release 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abraham, G., Solyom, S., Csuzdi, E., Berzsenyi, P., Ling, I., Tarnawa, I., Hamori, T., Pallagi, I., Horvath, K., Andrasi, F., Kapus, G., Harsing, L.G., Jr., and Kiraly, I., 2000, New non competitive AMPA antagonists, Bioorg. Med. Chem. 8:2127.Google Scholar
  2. Aghajanian, G.K., and Marek, G.J., 2000, Serotonin model of schizophrenia: emerging role of glutamate mechanisms, Brain Res. Rev. 31:302.Google Scholar
  3. Baldwin, H.A., Williams, J.L., Snares, M., Ferriera, T., Cross, A.J., Green, A.R., 1994, Attenuation by chlormethiazole of the rise in extracellular amino acids following focal ischemia in the cerebral cortex of the rat, Br. J. Pharmacol. 112:188.Google Scholar
  4. Beani, L., Tanganelli, S., Antonelli, T., Ferraro L., Morari, M., Spalluto, P., Nordberg, A., and Bianchi, C, 1991, Effect of acute and subchronic nicotine treatment on cortical efflux of [3H]-D-aspartate and endogenous GABA in freely moving guinea-pigs, Br. J. Pharmacol. 104:15.Google Scholar
  5. Bederson, J.B., Pitts, L.H., Gremano, S.M., Nishimura, M. C, Davis, R.L., and Bartkowski, H.M., 1986, Evaluation of 2,3,5-triphenyltetrazolium chloride as a stain for detection and quantification of experimental cerebral infarction in rats, Stroke 17:1304.Google Scholar
  6. Bolam, J.P., and Bennett, B.D., 1995, Microcircuitry of the neostriatum, in: Molecular and Cellular Mechanisms of Neurostriatal Function, M. A. Ariano, and D. J. Surmeier, EDS., Landes Company, Austin, TX, pp. 1–19.Google Scholar
  7. Carlsson, A., Hansson, L.O., Waters, N., and Carlsson, M.L., 1997, Neurotransmitter aberration in schizophrenia: new perspectives and therapeutic implications, Life Sci. 61:75.Google Scholar
  8. Chen, Q., Veenman, I., Knopp, K., Yan, Z., Medina, L., Song, W.-J., Surmeier, D.J., and Reiner, A., 1998, Evidence for the preferential location of glutamate receptor-1 subunits of AMPA receptors to the dendritic spines of medium spiny neurons in rat striatum, Neuroscience 83:749.Google Scholar
  9. Coyle, J.T., Puttfarcken, P., 1993, Oxidative stress, glutamate and neurodegenerative disorders, Science 262:689.Google Scholar
  10. Gajkowska, B., Mossakowski, M.J., 1994, Ischemia inhibits GABAergic neurons of the rat thalamic reticular nucleus. An immunocytochemical study, Folia Neuropathol, 32:139.Google Scholar
  11. Gerfen, C.R., The neostriatal mosaic: multiple levels of compartmental organization, TINS 15:133.Google Scholar
  12. Globus, M.Y.-Y., Busto, R., Martinez, E., Valdes, I., Dietrich, W.D., and Ginsberg, M.D., 1991, Comparative effect of transient global ischemia on extracellular levels of glutamate, glycine, and γ-aminobutyric acid in vulnerable and nonvulnerable brain regions in the rat, J. Neurochem. 57:470.Google Scholar
  13. Gonzales, C, Lin, R.C.-S., and Chesselet, M.-F., 1992, Relative sparing of GABAergic intemeurons in the striatum of gerbils with ischemia-induced lesions, Neurosci. Lett. 135:53.Google Scholar
  14. Harsing, L.G., Jr., Sershen, H., Lajtha, A., 1992, Dopamine efflux from striatum after chronic nicotine: evidence for autoreceptor desensitization, J. Neurochem. 59:48.Google Scholar
  15. Harsing, L.G., Jr., Zigmond, M.J., 1997, Influence of dopamine on GABA release in striatum: evidence for D1-D2 interactions and non-synaptic influences, Neuroscience 77:419.Google Scholar
  16. Harsing, L.G., Jr., Zigmond, M.J., 1998, Postsynaptic integration of cholinergic and dopaminergic signals on medium size GABAergic projection neurons in the neostriatum. Brain Res. Bull. 45:607.Google Scholar
  17. Harsing, L.G., Jr., Csillik-Perczel, V., Ling, I., and Solyom, S., 2000, Negative allosteric modulators of AMPA-preferring receptors inhibit [3H]GABA release in rat striatum, Neurochem. Internat. 37:33.Google Scholar
  18. Iversen, L.L., and Kelly, J.S., 1975, Uptake and metabolism of γ-aminobutyric acid by neurones and glial cells, Biochem. Pharmac. 24:933.Google Scholar
  19. Juranyi, Zs., Harsing, L.G., Jr., Zigmond, M.J., 2003, A new method for the investigation of transmitter release in complex corticostriatal slice preparation in vitro, J. Neurosci. Methods in press.Google Scholar
  20. Katsura, M., Lino, T., and Kuriyama, K., 1992, Changes in content of neuroactive amino acids and acetylcholine in the rat hippocampus following transient forebrain ischemia, Neurochem. Int. 21:243.Google Scholar
  21. Kawai, K, Penix, L.P., and Kawara, N., 1995, Development of susceptibility to audiogenic seizures following cardiac arrest cerebral ischemia, J. Cereb. Blood Flow Metab. 15:248.Google Scholar
  22. Kita, H., 1996, Glutamatergic and GABAergic postsynaptic responses of striatal spiny neurons to intrastriatal and cortical stimulation recorded in slice preparation. Neuroscience 70:925.Google Scholar
  23. Leyden, P.D., 1997, GABA and neuroprotection, Int. Rev. Neurohiol. 40:233.Google Scholar
  24. Longa, E.Z., Weinstein, P.R., Carlson S., and Cummins, R., 1989, Reversible middle cerebral artery occlusion craniectomy in rats, Stroke 28:84.Google Scholar
  25. Martin, R.L., Lloyd, H.G.E., and Cowan, A.I., 1994, The early events of oxygen and glucose deprivation: setting the scene for neural death? TINS 17:251.Google Scholar
  26. Miluseva, E., Doda, M., Pasztor, E., Lajtha, A., Sershen, H., and Vizi, E.S., 1992, Regulatory interactions among axon terminals affecting the release of different transmitters from rat striatal slices under hypoxic and hypoglycemic conditions, J. Neurochem. 69:946.Google Scholar
  27. Nelson, R.M., Green, A.R., Lambert, D.G., and Hainsworth, A.H., 2000, On the regulation of ischaemiainduced glutamate efflux from rat cortex by GABA; in vitro studies with GABA, clomethiazole and pentobarbitone, Br. J. Pharmacol. 130:1124.Google Scholar
  28. Nitsch, C, Goping, G., and Klatzo, I., 1989, Preservation of GABAergic perykaria and boutons after transient ischemia in the gerbil hippocampal CA1 field, Brain Res. 495:243.Google Scholar
  29. Parsons, C.G., Danysz, W., and Quack, G., 1998, Glutamate in CNS disorders as a target for drug development: An update, Drug News Perspect. 11:523.Google Scholar
  30. Phillis, J.W., Smith-Barbour, M., Perkins, L.M., O’Regan M.H., 1993, GYKI 52466 and ischemia-evoked neurotransmitter amino acid release from rat cerebral cortex, NeuroReport 4:109.Google Scholar
  31. Ren, Y., Li, X., and Xu, Z. C, 1997, Asymmetrical protection of neostriatal neurons against transient forebrain ischemia by unilateral dopamine depletion, Exp. Neurol. 146:250.Google Scholar
  32. Rowley, H.L., Martin, K.F., Marsden, C.A., 1995, Determination of in vivo amino acid neurotransmitters y high-performance liquid chromatography with o-phthalaldehyde-sulphite derivatisation, J. Neurosci. Methods, 54:93.Google Scholar
  33. Schwartz-Bloom, R.D., and Sah, R., 2001, γ-Aminobutyric acidA neurotransmission and cerebral ischemia, J. Neurochem. 77:353.Google Scholar
  34. Scif-El-Nasr, M., and Khattab, M., 2002, Influence of inhibition of adenosine uptake on the γ-aminobutyric acid level of the ischemic rat brain, Arzneim. Forsck/Drug Res. 52:353.Google Scholar
  35. Smith A.D., Bolam, J.P., 1990, The neural network of the basal ganglia as revealed by the study of synaptic connections of identified neurones, TINS 13:259.Google Scholar
  36. Snyder, G., Keller, R.W., Zigmond, M.J., 1990, Dopamine efflux from striatal slices after intracerebral 6-hydroxydopamine: evidence for compensatory hyperactivity of residual terminals, J. Pharm. Exp. Ther. 253:867.Google Scholar
  37. Sopala, M., Schweizer, S., Schaffer, N., Nurnberg, E., Kreuter, J., Sciller, E., and Danysz, W., 2002, Neuroprotective activity of a nanoparticulate formulation of the glycines site antagonist MRZ 2/576 in transient focal ischaemia in rats, Arzneim.-Forsch/Drug Res. 52:168.Google Scholar
  38. Szatkowski, M., Attwell, D., 1994, Triggering and execution of neural death in brain ischaemia: two phases of glutamate release by different mechanisms, TINS 17:359.Google Scholar
  39. Szerb, J. C, 1982. Effect of nipecotic acid, a γ-aminobutyric acid transport inhibitor, on the turnover and release of γ-aminobutyric acid in the rat cerebral cortex, J. Neurochem. 39:850.Google Scholar
  40. Taguchi, T., Miyake, K., and Tanonnaka, K., 1993, Sustained changes in acetylcholine and amino acid contents of brain regions following microsphere embolism in rats, Jpn. J. Pharmacol, 62:269Google Scholar
  41. Tamawa, I., Vizi, E.S., 1998, 2,3-Benzodiazepine AMPA antagonists, Rest. Neurol. Neurosci. 13:41.Google Scholar
  42. Vizi, E.S., Mike, A., and Tarnawa, I., 1996 2,3-Benzodiazepines (GYKI 52466 and analogs): negative allosteric modulators of AMPA receptors, CNS Drug Reviews 2:91.Google Scholar
  43. Warner, D.S., Martin, H., Ludwig, P., McAllister, A., Keane, J.F. W., and Weber, E., 1995, In vivo models of cerebral ischemia: effects of parenterally administered NMDA receptor glycine site antagonists, J. Cereb. Blood Flow and Metab. 15:188.Google Scholar
  44. Zigmond, M.J., Abercrombie, E.D., Berger, T.W., Grace A.A., and Strieker, E.M., 1990, Compensations after lesions of central dopaminergic neurons: some clinical and basic implication, TINS 13:290.Google Scholar
  45. Zoli, M., Grimaldi, R., Ferrari, R., Zini I, and Agnati, L.F., 1997, Short-and long-term changes in striatal neurons and astroglia after transient forebrain ischemia in rats, Stroke 28:1049.Google Scholar

Copyright information

© Springer Science+Business Media New York 2004

Authors and Affiliations

  • Laszlo G. HarsingJr.
    • 1
  • Gabor Gigler
    • 1
  • Mihaly Albert
    • 1
  • Gabor Szenasi
    • 1
  • Annamaria Simo
    • 1
  • Krisztina Moricz
    • 1
  • Attila Varga
    • 1
  • Istvan Ling
    • 1
  • Erzsebet Bagdy
    • 2
  • Istvan Kiraly
    • 2
  • Sandor Solyom
    • 2
  • Zsolt Juranyi
    • 1
  1. 1.IVAX Drug Research InstituteBudapestHungary
  2. 2.EGIS Pharmaceuticals Ltd.BudapestHungary

Personalised recommendations