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Proc Natl Acad Sci U S A. 1993 Jun 15; 90(12): 5662–5666.

Localized 1H NMR measurements of gamma-aminobutyric acid in human brain in vivo.


Localized 1H NMR spectroscopy in conjunction with J editing was used to measure the concentration of gamma-aminobutyric acid (GABA) in the occipital lobe of four control human volunteers and four epileptic volunteers who were receiving the drug vigabatrin. The GABA concentration measured in four nonepileptic subjects was 1.1 +/- 0.1 mumol/cm3 of brain, which is in good agreement with previous values measured in surgically removed human cortex. A dose-dependent elevation of GABA concentration was measured in patients receiving the GABA transaminase inhibitor vigabatrin, with the maximum measured level of 3.7 mumol/cm3 of brain measured at the highest dose (6 g per day) studied. 1H NMR measurements of GABA in those patients receiving GABA-elevating agents such as vigabatrin will be of importance in establishing the relationship between seizure suppression and the concentration of brain GABA.

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  • McCormick DA. GABA as an inhibitory neurotransmitter in human cerebral cortex. J Neurophysiol. 1989 Nov;62(5):1018–1027. [PubMed]
  • Meldrum BS. GABAergic mechanisms in the pathogenesis and treatment of epilepsy. Br J Clin Pharmacol. 1989;27 (Suppl 1):3S–11S. [PMC free article] [PubMed]
  • Horton RW, Collins JF, Anlezark GM, Meldrum BS. Convulsant and anticonvulsant actions in DBA/2 mice of compounds blocking the reuptake of GABA. Eur J Pharmacol. 1979 Oct 26;59(1-2):75–83. [PubMed]
  • Wood JD, Johnson DD, Krogsgaard-Larsen P, Schousboe A. Anticonvulsant activity of the glial-selective GABA uptake inhibitor, THPO. Neuropharmacology. 1983 Jan;22(1):139–142. [PubMed]
  • Frey HH, Popp C, Löscher W. Influence of inhibitors of the high affinity GABA uptake on seizure thresholds in mice. Neuropharmacology. 1979 Jul;18(7):581–590. [PubMed]
  • Palfreyman MG, Schechter PJ, Buckett WR, Tell GP, Koch-Weser J. The pharmacology of GABA-transaminase inhibitors. Biochem Pharmacol. 1981 Apr 15;30(8):817–824. [PubMed]
  • Meldrum B, Horton R. Blockade of epileptic responses in the photosensitive baboon, Papio papio, by two irreversible inhibitors of GABA-transaminase, gamma-acetylenic GABA (4-amino-hex-5-ynoic acid) and gamma-vinyl GABA (4-amino-hex-5-enoic acid). Psychopharmacology (Berl) 1978 Sep 15;59(1):47–50. [PubMed]
  • Shin C, Rigsbee LC, McNamara JO. Anti-seizure and anti-epileptogenic effect of gamma-vinyl gamma-aminobutyric acid in amygdaloid kindling. Brain Res. 1986 Nov 29;398(2):370–374. [PubMed]
  • Lippert B, Metcalf BW, Jung MJ, Casara P. 4-amino-hex-5-enoic acid, a selective catalytic inhibitor of 4-aminobutyric-acid aminotransferase in mammalian brain. Eur J Biochem. 1977 Apr 15;74(3):441–445. [PubMed]
  • Gram L, Larsson OM, Johnsen A, Schousboe A. Experimental studies of the influence of vigabatrin on the GABA system. Br J Clin Pharmacol. 1989;27 (Suppl 1):13S–17S. [PMC free article] [PubMed]
  • Bolton JB, Rimmer E, Williams J, Richens A. The effect of vigabatrin on brain and platelet GABA-transaminase activities. Br J Clin Pharmacol. 1989;27 (Suppl 1):35S–42S. [PMC free article] [PubMed]
  • Browne TR, Mattson RH, Penry JK, Smith DB, Treiman DM, Wilder BJ, Ben-Menachem E, Napoliello MJ, Sherry KM, Szabo GK. Vigabatrin for refractory complex partial seizures: multicenter single-blind study with long-term follow-up. Neurology. 1987 Feb;37(2):184–189. [PubMed]
  • Mumford JP, Dam M. Meta-analysis of European placebo controlled studies of vigabatrin in drug resistant epilepsy. Br J Clin Pharmacol. 1989;27 (Suppl 1):101S–107S. [PMC free article] [PubMed]
  • Remy C, Beaumont D. Efficacy and safety of vigabatrin in the long-term treatment of refractory epilepsy. Br J Clin Pharmacol. 1989;27 (Suppl 1):125S–129S. [PMC free article] [PubMed]
  • Sivenius J, Ylinen A, Murros K, Mumford JP, Riekkinen PJ. Vigabatrin in drug-resistant partial epilepsy: a 5-year follow-up study. Neurology. 1991 Apr;41(4):562–565. [PubMed]
  • Frisk-Holmberg M, Kerth P, Meyer P. Effect of food on the absorption of vigabatrin. Br J Clin Pharmacol. 1989;27 (Suppl 1):23S–25S. [PMC free article] [PubMed]
  • Behar KL, den Hollander JA, Stromski ME, Ogino T, Shulman RG, Petroff OA, Prichard JW. High-resolution 1H nuclear magnetic resonance study of cerebral hypoxia in vivo. Proc Natl Acad Sci U S A. 1983 Aug;80(16):4945–4948. [PMC free article] [PubMed]
  • Rothman DL, Behar KL, Hetherington HP, Shulman RG. Homonuclear 1H double-resonance difference spectroscopy of the rat brain in vivo. Proc Natl Acad Sci U S A. 1984 Oct;81(20):6330–6334. [PMC free article] [PubMed]
  • Behar KL, Ogino T. Assignment of resonance in the 1H spectrum of rat brain by two-dimensional shift correlated and J-resolved NMR spectroscopy. Magn Reson Med. 1991 Feb;17(2):285–303. [PubMed]
  • Hanstock CC, Rothman DL, Prichard JW, Jue T, Shulman RG. Spatially localized 1H NMR spectra of metabolites in the human brain. Proc Natl Acad Sci U S A. 1988 Mar;85(6):1821–1825. [PMC free article] [PubMed]
  • Segebarth CM, Balériaux DF, Luyten PR, den Hollander JA. Detection of metabolic heterogeneity of human intracranial tumors in vivo by 1H NMR spectroscopic imaging. Magn Reson Med. 1990 Jan;13(1):62–76. [PubMed]
  • Rothman DL, Hanstock CC, Petroff OA, Novotny EJ, Prichard JW, Shulman RG. Localized 1H NMR spectra of glutamate in the human brain. Magn Reson Med. 1992 May;25(1):94–106. [PubMed]
  • Rothman DL, Novotny EJ, Shulman GI, Howseman AM, Petroff OA, Mason G, Nixon T, Hanstock CC, Prichard JW, Shulman RG. 1H-[13C] NMR measurements of [4-13C]glutamate turnover in human brain. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9603–9606. [PMC free article] [PubMed]
  • Silver MS, Joseph RI, Chen CN, Sank VJ, Hoult DI. Selective population inversion in NMR. Nature. 1984 Aug 23;310(5979):681–683. [PubMed]
  • Spencer SS. Surgical options for uncontrolled epilepsy. Neurol Clin. 1986 Aug;4(3):669–695. [PubMed]
  • Browne TR, Mattson RH, Penry JK, Smith DB, Treiman DM, Wilder BJ, Ben-Menachem E, Miketta RM, Sherry KM, Szabo GK. A multicentre study of vigabatrin for drug-resistant epilepsy. Br J Clin Pharmacol. 1989;27 (Suppl 1):95S–100S. [PMC free article] [PubMed]
  • Browne TR, Mattson RH, Penry JK, Smith DB, Treiman DM, Wilder BJ, Ben-Menachem E, McBride RG, Sherry KM. Multicenter long-term safety and efficacy study of vigabatrin for refractory complex partial seizures: an update. Neurology. 1991 Mar;41(3):363–364. [PubMed]
  • Gruetter R, Rothman DL, Novotny EJ, Shulman GI, Prichard JW, Shulman RG. Detection and assignment of the glucose signal in 1H NMR difference spectra of the human brain. Magn Reson Med. 1992 Sep;27(1):183–188. [PubMed]
  • Prichard J, Rothman D, Novotny E, Petroff O, Kuwabara T, Avison M, Howseman A, Hanstock C, Shulman R. Lactate rise detected by 1H NMR in human visual cortex during physiologic stimulation. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5829–5831. [PMC free article] [PubMed]
  • Chen W, Ackerman JJ. Surface coil single-pulse localization in vivo via inhomogeneous surface spoiling magnetic gradient. NMR Biomed. 1989 Apr;1(4):205–207. [PubMed]
  • Bottomley PA, Edelstein WA, Foster TH, Adams WA. In vivo solvent-suppressed localized hydrogen nuclear magnetic resonance spectroscopy: a window to metabolism? Proc Natl Acad Sci U S A. 1985 Apr;82(7):2148–2152. [PMC free article] [PubMed]
  • Hetherington HP, Avison MJ, Shulman RG. 1H homonuclear editing of rat brain using semiselective pulses. Proc Natl Acad Sci U S A. 1985 May;82(10):3115–3118. [PMC free article] [PubMed]
  • Petroff OA, Spencer DD, Alger JR, Prichard JW. High-field proton magnetic resonance spectroscopy of human cerebrum obtained during surgery for epilepsy. Neurology. 1989 Sep;39(9):1197–1202. [PubMed]
  • Lowry OH, Berger SJ, Chi MM, Carter JG, Blackshaw A, Outlaw W. Diversity of metabolic patterns in human brain tumors--I. High energy phosphate compounds and basic composition. J Neurochem. 1977 Dec;29(6):959–977. [PubMed]
  • Gill SS, Thomas DG, Van Bruggen N, Gadian DG, Peden CJ, Bell JD, Cox IJ, Menon DK, Iles RA, Bryant DJ, et al. Proton MR spectroscopy of intracranial tumours: in vivo and in vitro studies. J Comput Assist Tomogr. 1990 Jul-Aug;14(4):497–504. [PubMed]
  • Van Gelder NM, Sherwin AL, Rasmussen T. Amino acid content of epileptogenic human brain: focal versus surrounding regions. Brain Res. 1972 May 26;40(2):385–393. [PubMed]
  • Perry TL, Hansen S, Gandham SS. Postmortem changes of amino compounds in human and rat brain. J Neurochem. 1981 Feb;36(2):406–410. [PubMed]
  • Schechter PJ, Hanke NF, Grove J, Huebert N, Sjoerdsma A. Biochemical and clinical effects of gamma-vinyl GABA in patients with epilepsy. Neurology. 1984 Feb;34(2):182–186. [PubMed]
  • Ben-Menachem E. Pharmacokinetic effects of vigabatrin on cerebrospinal fluid amino acids in humans. Epilepsia. 1989;30 (Suppl 3):S12–S14. [PubMed]
  • Riekkinen PJ, Ylinen A, Halonen T, Sivenius J, Pitkanen A. Cerebrospinal fluid GABA and seizure control with vigabatrin. Br J Clin Pharmacol. 1989;27 (Suppl 1):87S–94S. [PMC free article] [PubMed]

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