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. 2002 Jan;72(1):99–105. doi: 10.1136/jnnp.72.1.99

Increases in GABA concentrations during cerebral ischaemia: a microdialysis study of extracellular amino acids

P Hutchinson 1, M O'Connell 1, P Al-Rawi 1, C Kett-White 1, A Gupta 1, L Maskell 1, J Pickard 1, P Kirkpatrick 1
PMCID: PMC1737714  PMID: 11784833

Abstract

Objectives: Increases in the extracellular concentration of the excitatory amino acids glutamate and aspartate during cerebral ischaemia in patients are well recognised. Less emphasis has been placed on the concentrations of the inhibitory amino acid neurotransmitters, notably γ-amino-butyric acid (GABA), despite evidence from animal studies that GABA may act as a neuroprotectant in models of ischaemia. The objective of this study was to investigate the concentrations of various excitatory, inhibitory and non-transmitter amino acids under basal conditions and during periods of cerebral ischaemia in patients with head injury or a subarachnoid haemorrhage.

Methods: Cerebral microdialysis was established in 12 patients with head injury (n=7) or subarachnoid haemorrhage (n=5). Analysis was performed using high performance liquid chromatography for a total of 19 (excitatory, inhibitory and non-transmitter) amino acids. Patients were monitored in neurointensive care or during aneurysm clipping.

Results: During stable periods of monitoring the concentrations of amino acids were relatively constant enabling basal values to be established. In six patients, cerebral ischaemia was associated with increases (up to 1350 fold) in the concentration of GABA, in addition to the glutamate and aspartate. Parallel increases in the concentration of glutamate and GABA were found (r=0.71, p<0.005).

Conclusions: The results suggest that, in the human brain, acute cerebral ischaemia is not accompanied by an imbalance between excitatory and inhibitory amino acids, but by an increase in all neurotransmitter amino acids. These findings concur with the animal models of ischaemia and raise the possibility of an endogenous GABA mediated neuroprotective mechanism in humans.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Antkowiak B. Different actions of general anesthetics on the firing patterns of neocortical neurons mediated by the GABA(A) receptor. Anesthesiology. 1999 Aug;91(2):500–511. doi: 10.1097/00000542-199908000-00025. [DOI] [PubMed] [Google Scholar]
  2. Baldwin H. A., Williams J. L., Snares M., Ferreira T., Cross A. J., Green A. R. Attenuation by chlormethiazole administration of the rise in extracellular amino acids following focal ischaemia in the cerebral cortex of the rat. Br J Pharmacol. 1994 May;112(1):188–194. doi: 10.1111/j.1476-5381.1994.tb13050.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Belelli D., Pistis M., Peters J. A., Lambert J. J. The interaction of general anaesthetics and neurosteroids with GABA(A) and glycine receptors. Neurochem Int. 1999 May;34(5):447–452. doi: 10.1016/s0197-0186(99)00037-6. [DOI] [PubMed] [Google Scholar]
  4. Benveniste H., Drejer J., Schousboe A., Diemer N. H. Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J Neurochem. 1984 Nov;43(5):1369–1374. doi: 10.1111/j.1471-4159.1984.tb05396.x. [DOI] [PubMed] [Google Scholar]
  5. Bourdelais A. J., Kalivas P. W. Modulation of extracellular gamma-aminobutyric acid in the ventral pallidum using in vivo microdialysis. J Neurochem. 1992 Jun;58(6):2311–2320. doi: 10.1111/j.1471-4159.1992.tb10979.x. [DOI] [PubMed] [Google Scholar]
  6. Bullock R. Excitatory amino acids following brain injury. J Neurosurg. 1994 Mar;80(3):595–596. doi: 10.3171/jns.1994.80.3.0595. [DOI] [PubMed] [Google Scholar]
  7. Bullock R., Zauner A., Woodward J. J., Myseros J., Choi S. C., Ward J. D., Marmarou A., Young H. F. Factors affecting excitatory amino acid release following severe human head injury. J Neurosurg. 1998 Oct;89(4):507–518. doi: 10.3171/jns.1998.89.4.0507. [DOI] [PubMed] [Google Scholar]
  8. Butcher S. P., Bullock R., Graham D. I., McCulloch J. Correlation between amino acid release and neuropathologic outcome in rat brain following middle cerebral artery occlusion. Stroke. 1990 Dec;21(12):1727–1733. doi: 10.1161/01.str.21.12.1727. [DOI] [PubMed] [Google Scholar]
  9. Bächli H., Langemann H., Mendelowitsch A., Alessandri B., Landolt H., Gratzl O. Microdialytic monitoring during cerebrovascular surgery. Neurol Res. 1996 Aug;18(4):370–376. doi: 10.1080/01616412.1996.11740439. [DOI] [PubMed] [Google Scholar]
  10. Campbell K., Kalén P., Lundberg C., Wictorin K., Rosengren E., Björklund A. Extracellular gamma-aminobutyric acid levels in the rat caudate-putamen: monitoring the neuronal and glial contribution by intracerebral microdialysis. Brain Res. 1993 Jun 18;614(1-2):241–250. doi: 10.1016/0006-8993(93)91041-p. [DOI] [PubMed] [Google Scholar]
  11. Choi D. W., Maulucci-Gedde M., Kriegstein A. R. Glutamate neurotoxicity in cortical cell culture. J Neurosci. 1987 Feb;7(2):357–368. doi: 10.1523/JNEUROSCI.07-02-00357.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cross A. J., Jones J. A., Baldwin H. A., Green A. R. Neuroprotective activity of chlormethiazole following transient forebrain ischaemia in the gerbil. Br J Pharmacol. 1991 Oct;104(2):406–411. doi: 10.1111/j.1476-5381.1991.tb12443.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Davies P. A., Hanna M. C., Hales T. G., Kirkness E. F. Insensitivity to anaesthetic agents conferred by a class of GABA(A) receptor subunit. Nature. 1997 Feb 27;385(6619):820–823. doi: 10.1038/385820a0. [DOI] [PubMed] [Google Scholar]
  14. Doppenberg E. M., Bullock R. Clinical neuro-protection trials in severe traumatic brain injury: lessons from previous studies. J Neurotrauma. 1997 Feb;14(2):71–80. doi: 10.1089/neu.1997.14.71. [DOI] [PubMed] [Google Scholar]
  15. Doppenberg E. M., Choi S. C., Bullock R. Clinical trials in traumatic brain injury. What can we learn from previous studies? Ann N Y Acad Sci. 1997 Oct 15;825:305–322. doi: 10.1111/j.1749-6632.1997.tb48441.x. [DOI] [PubMed] [Google Scholar]
  16. During M. J., Spencer D. D. Extracellular hippocampal glutamate and spontaneous seizure in the conscious human brain. Lancet. 1993 Jun 26;341(8861):1607–1610. doi: 10.1016/0140-6736(93)90754-5. [DOI] [PubMed] [Google Scholar]
  17. Fink-Jensen A., Suzdak P. D., Swedberg M. D., Judge M. E., Hansen L., Nielsen P. G. The gamma-aminobutyric acid (GABA) uptake inhibitor, tiagabine, increases extracellular brain levels of GABA in awake rats. Eur J Pharmacol. 1992 Sep 22;220(2-3):197–201. doi: 10.1016/0014-2999(92)90748-s. [DOI] [PubMed] [Google Scholar]
  18. Globus M. Y., Busto R., Dietrich W. D., Martinez E., Valdes I., Ginsberg M. D. Effect of ischemia on the in vivo release of striatal dopamine, glutamate, and gamma-aminobutyric acid studied by intracerebral microdialysis. J Neurochem. 1988 Nov;51(5):1455–1464. doi: 10.1111/j.1471-4159.1988.tb01111.x. [DOI] [PubMed] [Google Scholar]
  19. Graham S. H., Shiraishi K., Panter S. S., Simon R. P., Faden A. I. Changes in extracellular amino acid neurotransmitters produced by focal cerebral ischemia. Neurosci Lett. 1990 Mar 2;110(1-2):124–130. doi: 10.1016/0304-3940(90)90799-f. [DOI] [PubMed] [Google Scholar]
  20. Green A. R., Misra A., Hewitt K. E., Snape M. F., Cross A. J. An investigation of the possible interaction of clomethiazole with glutamate and ion channel sites as an explanation of its neuroprotective activity. Pharmacol Toxicol. 1998 Aug;83(2):90–94. doi: 10.1111/j.1600-0773.1998.tb01449.x. [DOI] [PubMed] [Google Scholar]
  21. Hagberg H., Andersson P., Kjellmer I., Thiringer K., Thordstein M. Extracellular overflow of glutamate, aspartate, GABA and taurine in the cortex and basal ganglia of fetal lambs during hypoxia-ischemia. Neurosci Lett. 1987 Aug 5;78(3):311–317. doi: 10.1016/0304-3940(87)90379-x. [DOI] [PubMed] [Google Scholar]
  22. Hagberg H., Lehmann A., Sandberg M., Nyström B., Jacobson I., Hamberger A. Ischemia-induced shift of inhibitory and excitatory amino acids from intra- to extracellular compartments. J Cereb Blood Flow Metab. 1985 Sep;5(3):413–419. doi: 10.1038/jcbfm.1985.56. [DOI] [PubMed] [Google Scholar]
  23. Hillered L., Hallström A., Segersvärd S., Persson L., Ungerstedt U. Dynamics of extracellular metabolites in the striatum after middle cerebral artery occlusion in the rat monitored by intracerebral microdialysis. J Cereb Blood Flow Metab. 1989 Oct;9(5):607–616. doi: 10.1038/jcbfm.1989.87. [DOI] [PubMed] [Google Scholar]
  24. Hillered L., Persson L., Pontén U., Ungerstedt U. Neurometabolic monitoring of the ischaemic human brain using microdialysis. Acta Neurochir (Wien) 1990;102(3-4):91–97. doi: 10.1007/BF01405420. [DOI] [PubMed] [Google Scholar]
  25. Hollrigel G. S., Toth K., Soltesz I. Neuroprotection by propofol in acute mechanical injury: role of GABAergic inhibition. J Neurophysiol. 1996 Oct;76(4):2412–2422. doi: 10.1152/jn.1996.76.4.2412. [DOI] [PubMed] [Google Scholar]
  26. Hutchinson P. J., Al-Rawi P. G., O'Connell M. T., Gupta A. K., Maskell L. B., Hutchinson D. B., Pickard J. D., Kirkpatrick P. J. Monitoring of brain metabolism during aneurysm surgery using microdialysis and brain multiparameter sensors. Neurol Res. 1999 Jun;21(4):352–358. doi: 10.1080/01616412.1999.11740943. [DOI] [PubMed] [Google Scholar]
  27. Hutchinson P. J., Hutchinson D. B., Barr R. H., Burgess F., Kirkpatrick P. J., Pickard J. D. A new cranial access device for cerebral monitoring. Br J Neurosurg. 2000 Feb;14(1):46–48. doi: 10.1080/02688690042915. [DOI] [PubMed] [Google Scholar]
  28. Hutchinson P. J., O'Connell M. T., Al-Rawi P. G., Maskell L. B., Kett-White R., Gupta A. K., Richards H. K., Hutchinson D. B., Kirkpatrick P. J., Pickard J. D. Clinical cerebral microdialysis: a methodological study. J Neurosurg. 2000 Jul;93(1):37–43. doi: 10.3171/jns.2000.93.1.0037. [DOI] [PubMed] [Google Scholar]
  29. Hutchinson P. J., al-Rawi P. G., O'Connell M. T., Gupta A. K., Maskell L. B., Hutchinson D. B., Pickard J. D., Kirkpatrick P. J. On-line monitoring of substrate delivery and brain metabolism in head injury. Acta Neurochir Suppl. 2000;76:431–435. doi: 10.1007/978-3-7091-6346-7_89. [DOI] [PubMed] [Google Scholar]
  30. Jennett B., Bond M. Assessment of outcome after severe brain damage. Lancet. 1975 Mar 1;1(7905):480–484. doi: 10.1016/s0140-6736(75)92830-5. [DOI] [PubMed] [Google Scholar]
  31. Johansen F. F., Diemer N. H. Enhancement of GABA neurotransmission after cerebral ischemia in the rat reduces loss of hippocampal CA1 pyramidal cells. Acta Neurol Scand. 1991 Jul;84(1):1–6. doi: 10.1111/j.1600-0404.1991.tb04893.x. [DOI] [PubMed] [Google Scholar]
  32. Kanthan R., Shuaib A. Clinical evaluation of extracellular amino acids in severe head trauma by intracerebral in vivo microdialysis. J Neurol Neurosurg Psychiatry. 1995 Sep;59(3):326–327. doi: 10.1136/jnnp.59.3.326. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Kanthan R., Shuaib A., Griebel R., Miyashita H. Intracerebral human microdialysis. In vivo study of an acute focal ischemic model of the human brain. Stroke. 1995 May;26(5):870–873. doi: 10.1161/01.str.26.5.870. [DOI] [PubMed] [Google Scholar]
  34. Krasowski M. D., Koltchine V. V., Rick C. E., Ye Q., Finn S. E., Harrison N. L. Propofol and other intravenous anesthetics have sites of action on the gamma-aminobutyric acid type A receptor distinct from that for isoflurane. Mol Pharmacol. 1998 Mar;53(3):530–538. doi: 10.1124/mol.53.3.530. [DOI] [PubMed] [Google Scholar]
  35. Lynch D. R., Dawson T. M. Secondary mechanisms in neuronal trauma. Curr Opin Neurol. 1994 Dec;7(6):510–516. doi: 10.1097/00019052-199412000-00007. [DOI] [PubMed] [Google Scholar]
  36. Massieu L., Morales-Villagrán A., Tapia R. Accumulation of extracellular glutamate by inhibition of its uptake is not sufficient for inducing neuronal damage: an in vivo microdialysis study. J Neurochem. 1995 May;64(5):2262–2272. doi: 10.1046/j.1471-4159.1995.64052262.x. [DOI] [PubMed] [Google Scholar]
  37. Matsumoto K., Lo E. H., Pierce A. R., Halpern E. F., Newcomb R. Secondary elevation of extracellular neurotransmitter amino acids in the reperfusion phase following focal cerebral ischemia. J Cereb Blood Flow Metab. 1996 Jan;16(1):114–124. doi: 10.1097/00004647-199601000-00014. [DOI] [PubMed] [Google Scholar]
  38. Meldrum B., Evans M., Griffiths T., Simon R. Ischaemic brain damage: the role of excitatory activity and of calcium entry. Br J Anaesth. 1985 Jan;57(1):44–46. doi: 10.1093/bja/57.1.44. [DOI] [PubMed] [Google Scholar]
  39. Mendelowitsch A., Sekhar L. N., Wright D. C., Nadel A., Miyashita H., Richardson R., Kent M., Shuaib A. An increase in extracellular glutamate is a sensitive method of detecting ischaemic neuronal damage during cranial base and cerebrovascular surgery. An in vivo microdialysis study. Acta Neurochir (Wien) 1998;140(4):349–356. doi: 10.1007/s007010050108. [DOI] [PubMed] [Google Scholar]
  40. Meyerson B. A., Linderoth B., Karlsson H., Ungerstedt U. Microdialysis in the human brain: extracellular measurements in the thalamus of parkinsonian patients. Life Sci. 1990;46(4):301–308. doi: 10.1016/0024-3205(90)90037-r. [DOI] [PubMed] [Google Scholar]
  41. Nakata N., Kato H., Kogure K. Effects of repeated cerebral ischemia on extracellular amino acid concentrations measured with intracerebral microdialysis in the gerbil hippocampus. Stroke. 1993 Mar;24(3):458–464. doi: 10.1161/01.str.24.3.458. [DOI] [PubMed] [Google Scholar]
  42. Obrenovitch T. P., Urenjak J. Altered glutamatergic transmission in neurological disorders: from high extracellular glutamate to excessive synaptic efficacy. Prog Neurobiol. 1997 Jan;51(1):39–87. doi: 10.1016/s0301-0082(96)00049-4. [DOI] [PubMed] [Google Scholar]
  43. Obrenovitch T. P., Urenjak J. Is high extracellular glutamate the key to excitotoxicity in traumatic brain injury? J Neurotrauma. 1997 Oct;14(10):677–698. doi: 10.1089/neu.1997.14.677. [DOI] [PubMed] [Google Scholar]
  44. Olney J. W. Glutamate-induced neuronal necrosis in the infant mouse hypothalamus. An electron microscopic study. J Neuropathol Exp Neurol. 1971 Jan;30(1):75–90. doi: 10.1097/00005072-197101000-00008. [DOI] [PubMed] [Google Scholar]
  45. Orser B. A., McAdam L. C., Roder S., MacDonald J. F. General anaesthetics and their effects on GABA(A) receptor desensitization. Toxicol Lett. 1998 Nov 23;100-101:217–224. doi: 10.1016/s0378-4274(98)00188-x. [DOI] [PubMed] [Google Scholar]
  46. Palmer A. M., Marion D. W., Botscheller M. L., Bowen D. M., DeKosky S. T. Increased transmitter amino acid concentration in human ventricular CSF after brain trauma. Neuroreport. 1994 Dec 30;6(1):153–156. doi: 10.1097/00001756-199412300-00039. [DOI] [PubMed] [Google Scholar]
  47. Persson L., Hillered L. Chemical monitoring of neurosurgical intensive care patients using intracerebral microdialysis. J Neurosurg. 1992 Jan;76(1):72–80. doi: 10.3171/jns.1992.76.1.0072. [DOI] [PubMed] [Google Scholar]
  48. Persson L., Valtysson J., Enblad P., Warme P. E., Cesarini K., Lewen A., Hillered L. Neurochemical monitoring using intracerebral microdialysis in patients with subarachnoid hemorrhage. J Neurosurg. 1996 Apr;84(4):606–616. doi: 10.3171/jns.1996.84.4.0606. [DOI] [PubMed] [Google Scholar]
  49. Potashner S. J. Baclofen: effects on amino acid release and metabolism in slices of guinea pig cerebral cortex. J Neurochem. 1979 Jan;32(1):103–109. doi: 10.1111/j.1471-4159.1979.tb04516.x. [DOI] [PubMed] [Google Scholar]
  50. Ravindran J., Shuaib A., Ijaz S., Galazka P., Waqar T., Ishaqzay R., Miyashita H., Liu L. High extracellular GABA levels in hippocampus--as a mechanism of neuronal protection in cerebral ischemia in adrenalectomized gerbils. Neurosci Lett. 1994 Aug 1;176(2):209–211. doi: 10.1016/0304-3940(94)90084-1. [DOI] [PubMed] [Google Scholar]
  51. Robertson C. S., Gopinath S. P., Uzura M., Valadka A. B., Goodman J. C. Metabolic changes in the brain during transient ischemia measured with microdialysis. Neurol Res. 1998;20 (Suppl 1):S91–S94. doi: 10.1080/01616412.1998.11740618. [DOI] [PubMed] [Google Scholar]
  52. Rothman S. Synaptic release of excitatory amino acid neurotransmitter mediates anoxic neuronal death. J Neurosci. 1984 Jul;4(7):1884–1891. doi: 10.1523/JNEUROSCI.04-07-01884.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Saji M., Reis D. J. Delayed transneuronal death of substantia nigra neurons prevented by gamma-aminobutyric acid agonist. Science. 1987 Jan 2;235(4784):66–69. doi: 10.1126/science.3798095. [DOI] [PubMed] [Google Scholar]
  54. Shuaib A., Ijaz S., Hasan S., Kalra J. Gamma-vinyl GABA prevents hippocampal and substantia nigra reticulata damage in repetitive transient forebrain ischemia. Brain Res. 1992 Sep 11;590(1-2):13–17. doi: 10.1016/0006-8993(92)91076-q. [DOI] [PubMed] [Google Scholar]
  55. Shuaib A., Ijaz S., Miyashita H., Mainprize T., Kanthan R. Progressive decrease in extracellular GABA concentrations in the post-ischemic period in the striatum: a microdialysis study. Brain Res. 1994 Dec 12;666(1):99–103. doi: 10.1016/0006-8993(94)90287-9. [DOI] [PubMed] [Google Scholar]
  56. Shuaib A., Mazagri R., Ijaz S. GABA agonist "muscimol" is neuroprotective in repetitive transient forebrain ischemia in gerbils. Exp Neurol. 1993 Oct;123(2):284–288. doi: 10.1006/exnr.1993.1160. [DOI] [PubMed] [Google Scholar]
  57. Siesjö B. K. Pathophysiology and treatment of focal cerebral ischemia. Part I: Pathophysiology. J Neurosurg. 1992 Aug;77(2):169–184. doi: 10.3171/jns.1992.77.2.0169. [DOI] [PubMed] [Google Scholar]
  58. Siesjö B. K. Pathophysiology and treatment of focal cerebral ischemia. Part II: Mechanisms of damage and treatment. J Neurosurg. 1992 Sep;77(3):337–354. doi: 10.3171/jns.1992.77.3.0337. [DOI] [PubMed] [Google Scholar]
  59. Smith S. E., Sharp T. An investigation of the origin of extracellular GABA in rat nucleus accumbens measured in vivo by microdialysis. J Neural Transm Gen Sect. 1994;97(2):161–171. doi: 10.1007/BF01277951. [DOI] [PubMed] [Google Scholar]
  60. Sternau L. L., Lust W. D., Ricci A. J., Ratcheson R. Role for gamma-aminobutyric acid in selective vulnerability in gerbils. Stroke. 1989 Feb;20(2):281–287. doi: 10.1161/01.str.20.2.281. [DOI] [PubMed] [Google Scholar]
  61. Sydserff S. G., Cross A. J., West K. J., Green A. R. The effect of chlormethiazole on neuronal damage in a model of transient focal ischaemia. Br J Pharmacol. 1995 Apr;114(8):1631–1635. doi: 10.1111/j.1476-5381.1995.tb14950.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Teasdale G. M., Braakman R., Cohadon F., Dearden M., Iannotti F., Karimi A., Lapierre F., Maas A., Murray G., Ohman J. The European Brain Injury Consortium. Nemo solus satis sapit: nobody knows enough alone. Acta Neurochir (Wien) 1997;139(9):797–803. doi: 10.1007/BF01411397. [DOI] [PubMed] [Google Scholar]
  63. Teasdale G. M., Drake C. G., Hunt W., Kassell N., Sano K., Pertuiset B., De Villiers J. C. A universal subarachnoid hemorrhage scale: report of a committee of the World Federation of Neurosurgical Societies. J Neurol Neurosurg Psychiatry. 1988 Nov;51(11):1457–1457. doi: 10.1136/jnnp.51.11.1457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Teasdale G. M., Graham D. I. Craniocerebral trauma: protection and retrieval of the neuronal population after injury. Neurosurgery. 1998 Oct;43(4):723–738. doi: 10.1097/00006123-199810000-00001. [DOI] [PubMed] [Google Scholar]
  65. Teasdale G., Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet. 1974 Jul 13;2(7872):81–84. doi: 10.1016/s0140-6736(74)91639-0. [DOI] [PubMed] [Google Scholar]
  66. Timmerman W., Westerink B. H. Brain microdialysis of GABA and glutamate: what does it signify? Synapse. 1997 Nov;27(3):242–261. doi: 10.1002/(SICI)1098-2396(199711)27:3<242::AID-SYN9>3.0.CO;2-D. [DOI] [PubMed] [Google Scholar]
  67. Timmerman W., Zwaveling J., Westerink B. H. Characterization of extracellular GABA in the substantia nigra reticulata by means of brain microdialysis. Naunyn Schmiedebergs Arch Pharmacol. 1992 Jun;345(6):661–665. doi: 10.1007/BF00164580. [DOI] [PubMed] [Google Scholar]
  68. Torp R., Arvin B., Le Peillet E., Chapman A. G., Ottersen O. P., Meldrum B. S. Effect of ischaemia and reperfusion on the extra- and intracellular distribution of glutamate, glutamine, aspartate and GABA in the rat hippocampus, with a note on the effect of the sodium channel blocker BW1003C87. Exp Brain Res. 1993;96(3):365–376. doi: 10.1007/BF00234106. [DOI] [PubMed] [Google Scholar]
  69. Uchiyama-Tsuyuki Y., Araki H., Yae T., Otomo S. Changes in the extracellular concentrations of amino acids in the rat striatum during transient focal cerebral ischemia. J Neurochem. 1994 Mar;62(3):1074–1078. doi: 10.1046/j.1471-4159.1994.62031074.x. [DOI] [PubMed] [Google Scholar]
  70. Ungerstedt U. Microdialysis--principles and applications for studies in animals and man. J Intern Med. 1991 Oct;230(4):365–373. doi: 10.1111/j.1365-2796.1991.tb00459.x. [DOI] [PubMed] [Google Scholar]
  71. Vespa P., Prins M., Ronne-Engstrom E., Caron M., Shalmon E., Hovda D. A., Martin N. A., Becker D. P. Increase in extracellular glutamate caused by reduced cerebral perfusion pressure and seizures after human traumatic brain injury: a microdialysis study. J Neurosurg. 1998 Dec;89(6):971–982. doi: 10.3171/jns.1998.89.6.0971. [DOI] [PubMed] [Google Scholar]
  72. Wahlgren N. G., Ranasinha K. W., Rosolacci T., Franke C. L., van Erven P. M., Ashwood T., Claesson L. Clomethiazole acute stroke study (CLASS): results of a randomized, controlled trial of clomethiazole versus placebo in 1360 acute stroke patients. Stroke. 1999 Jan;30(1):21–28. doi: 10.1161/01.str.30.1.21. [DOI] [PubMed] [Google Scholar]
  73. Westerink B. H., de Vries J. B. On the origin of extracellular GABA collected by brain microdialysis and assayed by a simplified on-line method. Naunyn Schmiedebergs Arch Pharmacol. 1989 Jun;339(6):603–607. doi: 10.1007/BF00168650. [DOI] [PubMed] [Google Scholar]
  74. Wilson C. L., Maidment N. T., Shomer M. H., Behnke E. J., Ackerson L., Fried I., Engel J., Jr Comparison of seizure related amino acid release in human epileptic hippocampus versus a chronic, kainate rat model of hippocampal epilepsy. Epilepsy Res. 1996 Dec;26(1):245–254. doi: 10.1016/s0920-1211(96)00057-5. [DOI] [PubMed] [Google Scholar]
  75. You Z. B., Pettersson E., Herrera-Marschitz M., Hökfelt T., Terenius L., Nylander I., Goiny M., Hughes J., O'Connor W. T., Ungerstedt U. Modulation of striatal aspartate and dynorphin B release by cholecystokinin (CCK-8) studied in vivo with microdialysis. Neuroreport. 1994 Nov 21;5(17):2301–2304. doi: 10.1097/00001756-199411000-00024. [DOI] [PubMed] [Google Scholar]
  76. Zhang J., Niu X. Changes of monoamines, purines and amino acids in rat striatum as measured by intercerebral microdialysis during ischemia/reperfusion. Chin Med Sci J. 1994 Dec;9(4):225–229. [PubMed] [Google Scholar]

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