|
Elson
M. Haas, M.D. |
Taurine, a lesser known amino acid, is not part of our muscle protein yet is important in metabolism, especially in the brain. It is essential in newborns, as they cannot make it. Adults can produce sulfur-containing taurine from cysteine with the help of pyridoxine, B6. It is possible that if not enough taurine is made in the body, especially if cysteine or B6 is deficient, it might be further required in the diet. In foods, it is high in meats and fish proteins.
Taurine functions in electrically active tissues such as the brain and heart to help stabilize cell membranes. It also has functions in the gallbladder, eyes, and blood vessels and appears to have some antioxidant and detoxifying activity. Taurine aids the movement of potassium, sodium, calcium, and magnesium in and out of cells and thus helps generate nerve impulses. Zinc seems to support this effect of taurine. Taurine is found in the central nervous system, skeletal muscle, and heart; it is very concentrated in the brain and high in the heart tissues.
Taurine is an inhibitory neurotransmitter, and its main use has been to help treat epilepsy and other excitable brain states, where it functions as a mild sedative. Research shows low taurine levels at seizure sites and its anti-convulsant effect comes from its ability to stabilize nerve cell membranes, which prevents the erratic firing of nerve cells. Doses for this effect are 500 mg. three times daily.
The cardiovascular dosage of taurine is higher. In Japan, taurine therapy is used in the treatment of ischemic heart disease with supplements of 5–6 grams daily in three divided doses. Low taurine and magnesium levels were found in patients after heart attacks. Taurine has potential in the treatment of arrhythmias, especially arrhythmias secondary to ischemia. People with congestive heart failure have also responded to a dosage of 2 grams three times daily with improved cardiac and respiratory function. Other possible cardiovascular uses of taurine include hypertension, possibly related to effects in the renin-angiotensin system of the kidneys, and in patients with high cholesterol levels. Taurine helps gallbladder function by forming tauracholate from bile acids; tauracholate helps increase cholesterol elimination in the bile.
Other possible uses for taurine include immune suppression (by sparing L-cysteine), visual problems and eye disease, cirrhosis and liver failure, depression, male infertility due to low sperm motility, and as a supplement for newborns and new mothers. Overall, the dosage used may range from 500 mg. to 5–6 grams, with the higher amounts needed for the cardiovascular problems and possibly epilepsy. Possible symptoms of toxicity from taurine supplementation include diarrhea and peptic ulcers.
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Taurine is an amino acid. It is vital to the proper utilization of sodium, magnesium, potassium, and calcium. Taurine has a protective effect upon the human brain. The amino acid taurine is used to treat anxiety, hyperactivity, poor brain function, hypoglycemia, epilepsy, hypertension, and seizures.
The levels of taurine found in children's brains is up to 4 times that in adult brains. Thus supplementation for adults or children with lower levels of taurine can boost brain function. Excessive losses of taurine thru urine can be caused by many metabolism disorders. The results of this taurine loss can be: physical or emotional stress, excessive consumption of alcohol, intestinal problems, cardiac arrhythmias, platelet disorders, and zinc deficiency.
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Taurine is one of the most abundant amino acids in the body. It is found in the central nervous system, skeletal muscle and is very concentrated in the brain and heart. It is synthesized from the amino acids Methionine and Cysteine, in conjunction with vitamin B6. Animal protein is a good source of Taurine, as it is not found in vegetable protein. Vegetarians with an unbalanced protein intake, and therefore deficient in methionine or cysteine may have difficulty manufacturing Taurine. Taurine is present in meats and animal products, but not in plant products.Taurine functions in electrically active tissues such as the brain and heart to help stabilize cell membranes. Taurine seems to inhibit and modulate neurotransmitters in the brain and helps to stabilize cell membranes. It also has functions in the gallbladder, eyes, and blood vessels and appears to have some antioxidant and detoxifying activity. Taurine aids the movement of potassium, sodium, calcium, and magnesium in and out of cells and thus helps generate nerve impulses. Zinc seems to support this effect of Taurine. There have been reports on the benefits of Taurine supplementation for epileptics. It has also been found to control motor tics, such as uncontrollable facial twitches. Taurines' effectiveness in epilepsy has been limited by its poor diffusion across the blood-brain barrier. Vitamin B6 aids this.
In Japan, Taurine therapy is used in the treatment of ischemic heart disease. Low Taurine and magnesium levels have been found in patients after heart attacks . Like magnesium, Taurine affects cell membrane electrical excitability by normalizing potassium flow in and out of heart muscle cells. Supplements decrease the tendency to develop potentially lethal abnormal heart arrythmias after heart attacks. People with congestive heart failure have also responded to supplementation with improved cardiac and respiratory function.
Taurine is necessary for the chemical reactions that produce normal vision, and deficiencies are associated with retinal degeneration. Besides protecting the retina, Taurine may help prevent and possibly reverse age-related cataracts. Low levels of Taurine and other sulphur containing amino acids are associated with high blood pressure, and Taurine supplements have been shown to lower blood pressure in some studies.
Other possible uses for Taurine supplementation include eye disease, cirrhosis, depression and male infertility due to low sperm motility and hypertension, and as a supplement for newborns and new mothers. It is maintaining the correct composition of bile and the solubility of cholesterol. It has been found to have an effect on blood sugar levels similar to insulin. Possible symptoms of toxicity include diarrhea and peptic ulcers. For those considering taurine supplements, taurine is known to have a calming or depressant effect on the central nervous system, and may impair short term memory.
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WHAT IS IT?
Taurine is an amino acid in which many people are deficient. It's found in meat but not in vegetables. It is nonessential and can be manufactured from cysteine, another amino acid that is even rarer in diets.
WHAT DOES IT DO?
Along with Magnesium, Taurine is deficient in heart attack victims. Taurine normalizes the electrical activity of the heart muscle, and Taurine decreases the chances of cardiac arrhythmias which lead to death. In Japan, Taurine is used to treat Congestive Heart Failure (CHF,) and in some studies is better than CoQ10 for certain heart functions. Taurine may lower blood pressure in some people. Nutritionist Robert Crayhon believes it to be the best blood pressure lowering substance available.
Taurine may protect against and possible reverse cataracts in the eyes.
Taurine also acts like insulin in the body and may have a beneficial effect on diabetes.
Large doses of Taurine (1000 mg 3 times daily) have anecdotally been beneficial in preventing grand mal epileptic seizures.
CAUTIONS
Taurine is a depressant and large doses may result in some loss of short term memory.
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PHYSIOLOGY:EPILEPSY: Taurine is a neuro-inhibitory neurotransmitter. In Orthomolecular Review it is pointed out "an insufficiency of neuro-inhibitory transmitters (i.e. Taurine) may cause over-excitation in certain portion of the brain resulting in convulsant and epileptic type seizures."
HEART MUSCLES: Why did people on the liquid\d protein diet develop irregularities associated with potassium depletion when most were on potent potassium supplements? Recent evidence suggests Taurine is the most critical substance in the osmotic regulation of calcium and potassium in heart muscle. As a matter of fact, Taurine comprises 50% of the free amino acid content of the heart, Liquid protein had no Taurine and very low amounts of its precursors, Cysteine and Methionine. Therefore the heart muscles were unable to contract without calcium an potassium.
CHOLESTEROL GALL STONES: To quote Dr. Jeffrey Bland in Orthomolecular Review, "90% of Taurine is eventually conjugated to bile ... and this prevents cholesterol gall stones."
MAY BE USEFUL IN THE FOLLOWING CONDITIONS:
Convulsion/Epilepsy, Heart Muscle irregularities, Gall Stones
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I'd come across references to the amino acid, taurine, being useful in treating seizures in several books on epilepsy, though I had never met anyone who used it. A little more than a year ago I came across an article by a woman who had very good results stopping her convulsions using taurine. After reading her account I began a search for information about it and how it may affect seizures.
What I found is taurine is highly concentrated in the tissues of the brain, liver, and eyes. Insufficient quantities of taurine impedes liver function and, in cats, leads to blindness. Its role in seizures is that taurine acts to stabilize cell walls so the neurons can fire off normally. Seizures result from random firing of nerve cells. Taurine used in quantity to treat epilepsy has only one known side effect, peptic ulcers, which clear up when taurine is discontinued [1] .
My small partial seizures I still did not have under control last year, and sometimes had several a day. The symptoms ranged from panic, to sensations of foul odors, visual disturbances, memory loss, and sickness in my gut. After reading what information was available, I began taking taurine in June. About a month later my mental state and perceptions had stabilized considerably. In August my long- standing digestive distress was easing and the frequency of seizures was much less.
By September, my seizures with the bizarre perceptual distortions had all but
ceased and I was able to get my first driver's license in fifteen years. Most
often taurine is used as an adjunct to medication, not a replacement in treating
seizures. I found few epilepsy groups on the web are aware of how effective
taurine supplementation can be or have much information about it. On the
epilepsy bulletin boards I found a few others who use it, though they had little
information to share. A fair amount of study on its function and usefulness has
been going on for years.
The reader may click here for a survey of the recent biomedical literature on
taurine and epilepsy.
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Taurine. Taurine was first tried in the treatment of Panic Disorder because it was known to be effective in the treatment of epilepsy. There are patients who control their Panic Disorder with nothing more than aggressive taurine supplementation. A number of other PD patients find that they can reduce their medication with the help of taurine supplementation.
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Taurine is an amino acid, one of the building blocks of proteins. Found in the nervous system and muscles, taurine is one of the most abundant amino acids in the body. It is thought to help regulate heartbeat, maintain cell membranes, and affect the release of neurotransmitters (chemicals that carry signals between nerve cells) in the brain.
6. Fukuyama Y, Ochiai Y. Therapeutic trial by taurine for intractable childhood epilepsies. Brain Dev. 1982;4:63–69.
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Unlike the familiar amino acids, taurine -- or L-taurine, to be more particular -- is not used as a building block in proteins. But it is called an "essential" amino acid because the human body, although it desperately needs it, cannot synthetize it; we must get it from our foods. But because taurine is not used for proteins, biochemists classify it as a conditionally essential amino acid.Record 1 of 21 in MEDLINE EXPRESS (R) 1999/01-1999/08
Whatever, research in more recent years suggests that faulty taurine in metabolism may be associated with certain kinds of epileptic seizures. Below are the results of 21 investigations on the subject. At the end of set of abstracts, the reader will find a short list of potentially interesting web sites.
TITLE: GABAB-receptor splice variants GB1a and GB1b in rat brain: developmental regulation, cellular distribution and extrasynaptic localization.
AUTHOR(S): Fritschy-JM; Meskenaite-V; Weinmann-O; Honer-M; Benke-D; Mohler-H
ADDRESS OF AUTHOR: Institute of Pharmacology, Swiss Federal Institute of Technology (ETH),University of Zurich, Switzerland. fritschy@pharma.unizh.ch
SOURCE (BIBLIOGRAPHIC CITATION): Eur-J-Neurosci. 1999 Mar; 11(3): 761-8
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: FRANCE
ABSTRACT: GABAB (gamma-aminobutyric acid)-receptors have been implicated in central nervous system (CNS) functions, e.g. cognition and pain perception, and dysfunctions including spasticity and absence epilepsy. To permit an analysis of the two known GABAB-receptor splice variants GABAB-R1a (GB1a) and GABAB-R1b (GB1b), their distribution pattern has been differentiated in the rat brain, using Western blotting and immunohistochemistry with isoform-specific antisera. During postnatal maturation, the expression of the two splice variants was differentially regulated with GB1a being preponderant at birth. In adult brain, GB1b-immunoreactivity (-IR) was predominant, and the two isoforms largely accounted for the pattern of GABAB-receptor binding sites in the brain. Receptor heterogeneity was pronounced in the hippocampus, where both isoforms occurred in CA1, but only GB1b in CA3. Similarly, in the cerebellum, GB1b was exclusively found in Purkinje cells in a zebrin-like pattern. The staining was most pronounced in Purkinje cell dendrites and spines. Using electron microscopy, over 80% of the spine profiles in which a synaptic contact with a parallel fibre was visible contained GB1b-IR at extrasynaptic sites. This subcellular localization is unrelated to GABAergic inputs, indicating that the role of GABAB-receptors in vivo extends beyond synaptic GABAergic neurotransmission and may, in the cerebellum, involve taurine as a ligand.
NAME OF SUBSTANCE: Azides; CGP-71872; GABA-Antagonists; Organophosphorus-Compounds; Receptors,-GABA-B; Taurine; GABA
Record 2 of 21 in MEDLINE EXPRESS (R) 1996-1998
TITLE: Therapeutic applications of taurine.
AUTHOR(S): Birdsall-TC
ADDRESS OF AUTHOR: Thorne Research, Inc., Dover, ID 83825, USA. tim@thorne.com
SOURCE (BIBLIOGRAPHIC CITATION): Altern-Med-Rev. 1998 Apr; 3(2): 128-36
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: Taurine is a conditionally-essential amino acid which is not utilized in protein synthesis, but rather is found free or in simple peptides. Taurine has been shown to be essential in certain aspects of mammalian development, and in vitro studies in various species have demonstrated that low levels of taurine are associated with various pathological lesions, including cardiomyopathy, retinal degeneration, and growth retardation, especially if deficiency occurs during development. Metabolic actions of taurine include: bile acid conjugation, detoxification, membrane stabilization, osmoregulation, and modulation of cellular calcium levels. Clinically, taurine has been used with varying degrees of success in the treatment of a wide variety of conditions, including: cardiovascular diseases, hypercholesterolemia, epilepsy and other seizure disorders, macular degeneration, Alzheimer's disease, hepatic disorders, alcoholism, and cystic fibrosis.
NAME OF SUBSTANCE: Taurine
Record 3 of 21 in MEDLINE EXPRESS (R) 1996-1998
TITLE: [Audiogenic epilepsy: a morphofunctional analysis]
AUTHOR(S): Batuev-AS; Bragina-TA; Aleksandrov-AS; Riabinskaia-EA
SOURCE (BIBLIOGRAPHIC CITATION): Zh-Vyssh-Nerv-Deiat-Im-I-P-Pavlova. 1997 Mar-Apr; 47(2): 431-8
LANGUAGE OF ARTICLE: RUSSIAN; NON-ENGLISH
COUNTRY OF PUBLICATION: RUSSIA
ABSTRACT: The rats of K-M line with high level of convulsive readiness to sound stimuli were tested. It was established that systemic application of epileptogenic stimulus evoked the decrease of level of convulsive readiness. The phenomena of habituation and normalization of animal behavior were revealed. The intraperitoneal injection of inhibitory transmitter--GABA and taurine (separately or in mixture) blocked the convulsive seizures. The functional influence by KCl-induced spreading depression in the cerebral cortex bilaterally impairs the inhibitory processes, but not the changes the form of epileptiform seizure. In neurophysiological experiments using microelectrophoresis technique it was shown that taurine as inhibitory agent is more effective when applied to dendritic layers II-III; GABA is more effective if it is applied on soma of cortical pyramidal cells. Using the electron microscopic methods, the following changes were observed during the clonic seizure: axo-dendritic and axo-spine synapses in rat auditory cortex were activated. After the habituation to the epileptogenic stimulus, some features evidencing the decrease of activity were observed in ultrastructure of synapses in layers II-III. In 2 days after that the majority of ultrastructural shifts were normalized. Role of calcium ions in generation of epileptic seizures and their depression as main factor of antiepileptic mechanisms is discussed.
NAME OF SUBSTANCE: Taurine; GABA; Potassium-Chloride
Record 4 of 21 in MEDLINE EXPRESS (R) 1996-1998
TITLE: Comparison of seizure related amino acid release in human epileptic hippocampus versus a chronic, kainate rat model of hippocampal epilepsy.
AUTHOR(S): Wilson-CL; Maidment-NT; Shomer-MH; Behnke-EJ; Ackerson-L; Fried-I; Engel-J Jr
ADDRESS OF AUTHOR: Department of Neurology, UCLA School of Medicine 90024, USA.
SOURCE (BIBLIOGRAPHIC CITATION): Epilepsy-Res. 1996 Dec; 26(1): 245-54
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: NETHERLANDS
ABSTRACT: Recent microdialysis studies of excitatory and inhibitory amino acid release associated with paroxysmal hippocampal activity have found significant increases in the hippocampus of epileptic patients, but minimal or variable increases in animal models. One possible reason for the difference is that the animal models employed in these studies have not adequately reflected the pathophysiology of human epilepsy. The present study sought to verify the amino acid release reported in human epileptic hippocampus and then employs animal studies using a chronic rat model of epilepsy, in which rats exhibit spontaneous seizure activity 3 to 4 months after injection of kainic acid into the hippocampus. In agreement with earlier reports, we found increases in glutamate, aspartate and GABA during seizures in human hippocampus. In addition we found increases in taurine which have not previously been reported. The chronic rat model shows increases in the same amino acids as in the human epileptic hippocampus, both during spontaneous seizures and stimulation evoked after-discharges (ADs). In contrast, minimal increases are elicited by hippocampal stimulation in control (non-kainate injected) animals. These results correlate with the degree of mossy fiber reorganization found in the dentate gyrus of kainate rats or epileptic humans.
NAME OF SUBSTANCE: Amino-Acids; Excitatory-Amino-Acids; Taurine; Kainic-Acid; GABA
Record 5 of 21 in MEDLINE EXPRESS (R) 1996-1998
TITLE: Amino-acid release from human cerebral cortex during simulated ischaemia in vitro.
AUTHOR(S): Hegstad-E; Berg-Johnsen-J; Haugstad-TS; Hauglie-Hanssen-E; Langmoen-IA
ADDRESS OF AUTHOR: Institute for Surgical Research, Rikshospitalet, University of Oslo, Norway.
SOURCE (BIBLIOGRAPHIC CITATION): Acta-Neurochir-Wien. 1996; 138(2): 234-41
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: AUSTRIA
ABSTRACT: The aim of the present study was to investigate the release of amino-acids in human cerebral cortex during membrane depolarization and simulated ischaemia (energy deprivation). Superfluous tissue from temporal Iobe resections for epilepsy was cut into 500 microns thick slices and incubated in vitro. Membrane depolarization with 50 mM K+ caused a release of glutamate, aspartate, GABA and glycine, but not glutamine or leucine. The release of glutamate and GABA was Ca(++)-dependent. Slices were exposed to simulated ischaemia (energy deprivation; ED) by combined glucose/oxygen deprivation. This caused a Ca(++)-independent release of glutamate, aspartate, GABA, glycine, and taurine which started after 8 min, peaked at the end or shortly after the 27 min period of ED, and returned to control levels within 11 min following termination of ED. Preloaded D-[3H]aspartate was released both during K(+)-stimulation and ED. Release of D-[3H]aspartate during ED was delayed compared to glutamate supporting an initial phase of synaptic glutamate release. Uptake of L-[3H]glutamate was increased during the period of glutamate release, suggesting passive diffusion across the cell membrane or enhanced transport efficacy in cellular elements with functioning uptake mechanisms.
NAME OF SUBSTANCE: Amino-Acids; Calcium
Record 6 of 21 in MEDLINE EXPRESS (R) 1993-1995
TITLE: Extracellular GABA in the ventrolateral thalamus of rats exhibiting spontaneous absence epilepsy: a microdialysis study.
AUTHOR(S): Richards-DA; Lemos-T; Whitton-PS; Bowery-NG
ADDRESS OF AUTHOR: Department of Pharmacology, School of Pharmacy, London, England.
SOURCE (BIBLIOGRAPHIC CITATION): J-Neurochem. 1995 Oct; 65(4): 1674-80
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: There is compelling evidence that excessive GABA-mediated inhibition may underlie the abnormal electrical activity, initiated in the thalamus, associated with epileptic absence seizures. In particular, the GABAB receptor subtype seems to play a critical role, because its antagonists are potent inhibitors of absence seizures, whereas its agonists exacerbate seizure activity. Using a validated rat model of absence epilepsy, we have previously found no evidence of abnormal GABAB receptor density or affinity in thalamic tissue. In the present study, we have used in vivo microdialysis to monitor changes in levels of extracellular GABA and other amino acids in this brain region. We have shown that basal extracellular levels of GABA and, to a lesser extent, taurine are increased when compared with values in nonepileptic controls. However, modifying GABAergic transmission with the GABAB agonist (-)-baclofen (2 mg/kg i.p.), the GABAB antagonist CGP-35348 (200 mg/kg i.p.), or the GABA uptake inhibitor tiagabine (100 microM) did not produce any further alteration in extracellular GABA levels, despite the ability of these compounds to increase (baclofen and tiagabine) or decrease (CGP-35348) seizure activity. These findings suggest that the increased basal GABA levels observed in this animal model are not simply a consequence of seizure activity but may contribute to the initiation of absence seizures.
NAME OF SUBSTANCE: GABA-Antagonists; Nipecotic-Acids; Organophosphorus-Compounds; Baclofen; tiagabine; CGP-35348; GABA; Potassium
Record 7 of 21 in MEDLINE EXPRESS (R) 1993-1995
TITLE: [Changes of amino acids release in rat's hippocampus during kainic acid induced epilepsy and acupuncture]
AUTHOR(S): Liu-J; Cheng-J
ADDRESS OF AUTHOR: National Laboratory of Medical Neurobiology, Department of Neurobiology, Shanghai Medical University, China.
SOURCE (BIBLIOGRAPHIC CITATION): Chen-Tzu-Yen-Chiu. 1995; 20(3): 50-4
LANGUAGE OF ARTICLE: CHINESE; NON-ENGLISH
COUNTRY OF PUBLICATION: CHINA
ABSTRACT: Changes of amino acids release in rat's hippocampus were studied by using push-pull perfusion and high performance liquid chromatography (HPLC) with fluorometric detection techniques during kainic acid (KA) induced epilepsy and acupuncture. The results indicated that the levels of glutamate, aspartate, glycine and GABA were statistically increased in hippocampus 40min after administration of KA. After EA treatment, there was marked elevation in the extracellular level of taurine. It's shown that the inhibitory effect of EA on epilepsy may be related to the increase of inhibitory amino acids's release in hippocampus.
NAME OF SUBSTANCE: Amino-Acids; Kainic-Acid
Record 8 of 21 in MEDLINE EXPRESS (R) 1993-1995
TITLE: Intracerebral human microdialysis. In vivo study of an acute focal ischemic model of the human brain.
AUTHOR(S): Kanthan-R; Shuaib-A; Griebel-R; Miyashita-H
ADDRESS OF AUTHOR: Department of Medicine (Neurology), Royal University Hospital, Saskatoon, Saskatchewan, Canada.
SOURCE (BIBLIOGRAPHIC CITATION): Stroke. 1995 May; 26(5): 870-3
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: BACKGROUND AND PURPOSE: In vivo microdialysis was introduced in 1982 as a technique to study cerebral neurochemistry in awake, freely moving animals. In small animals, bilateral carotid occlusion produces a 7- to 10-fold increase in extracellular glutamate concentrations. This rapidly falls with reperfusion. Increase in extracellular glutamate is currently believed to be a major factor in initiating neuronal injury. Glutamate antagonists are currently undergoing clinical trials in acute stroke. Human data on the extracellular levels of glutamate and other amino acids in the normal or ischemic brain are limited. In this communication we wish to report the extracellular concentrations of glutamate, serine, glutamine, glycine, taurine, alanine, and gamma-aminobutyric acid, as monitored by in vivo microdialysis, in the simulated ischemic model of the temporal lobe of the human brain. METHODS: Intracerebral microdialysis was carried out in five patients who underwent resection of the temporal lobe for intractable epilepsy. Surgical excision leads to an acute (from partial to total, ie, from incomplete to complete) ischemic state of the resected brain. This was our model to study the changes in human extracellular fluid during acute focal ischemic conditions. RESULTS: Extracellular glutamate concentrations were 15 to 30 mumol/L in the preischemic samples. This increased to 380.69 +/- 42.14 mumol/L with partial (incomplete) ischemia and reached a peak of 1781.67 +/- 292.34 mumol/L (> 100-fold) with total isolation of the temporal pole (complete ischemia). The levels fell to 394.52 +/- 72.93 mumol/L 20 minutes after resection. Similar trends were observed with the onset of ischemia in the dialysate levels of serine, glutamine, glycine, alanine, taurine, and gamma-aminobutyric acid. CONCLUSIONS: Our results show that there is a significant increase in extracellular glutamate and other neurotransmitters with ischemia in the temporal lobe model of the human brain. This increase is of a higher magnitude than that in small animals.
NAME OF SUBSTANCE: Amino-Acids; GABA; Glutamic-Acid
Record 9 of 21 in MEDLINE EXPRESS (R) 1993-1995
TITLE: Neuroactive amino acids in synaptosomes from focal and nonfocal temporal lobe tissue of patients with intractable complex partial seizures.
AUTHOR(S): Lleu-PL; Labiner-D; Weinand-M; Huxtable-RJ
ADDRESS OF AUTHOR: College of Medicine, University of Arizona Health Sciences Center, Tucson 85724.
SOURCE (BIBLIOGRAPHIC CITATION): Adv-Exp-Med-Biol. 1994; 359: 435-43
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
NAME OF SUBSTANCE: Amino-Acids; Taurine; GABA; Glutamine; Glutamic-Acid
Record 10 of 21 in MEDLINE EXPRESS (R) 1993-1995
TITLE: Plasma amino acid alterations in idiopathic generalized epilepsy: an investigation in probands and their first-degree relatives.
AUTHOR(S): Monaco-F; Gianelli-M; Schiavella-MP; Naldi-P; Cantello-R; Torta-R; Verze-L; Mutani-R
ADDRESS OF AUTHOR: Clinica Neurologica, Universita di Sassari.
SOURCE (BIBLIOGRAPHIC CITATION): Ital-J-Neurol-Sci. 1994 Apr; 15(3): 137-44
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: ITALY
ABSTRACT: Twenty-two plasma amino acids were determined by means of ion-exchange chromatography in 16 previously untreated patients with generalized idiopathic epilepsy and in some of their first-degree relatives (26 subjects), and the results were compared with those obtained from a group of 50 healthy controls. The patients were subsequently treated with valproic acid for one month and then reexamined. In the epileptic subjects, statistical analysis showed significant alterations in the plasma levels of a group of amino acids, including the four associated with neuro-transmission (aspartate, glutamate, glycine, taurine); aspartate, glutamate and glycine levels were also altered in the first-degree relatives. Valproic acid therapy did not affect amino acid levels. If further confirmed, these alterations might be considered possible neurochemical markers of epilepsy.
NAME OF SUBSTANCE: Amino-Acids; Glutamates; Taurine; Glycine; Aspartic-Acid; Valproic-Acid
Record 11 of 21 in MEDLINE EXPRESS (R) 1993-1995
TITLE: A microdialysis study of amino acid concentrations in the extracellular fluid of the substantia nigra of freely behaving GEPR-9s: relationship to seizure predisposition.
AUTHOR(S): Doretto-MC; Burger-RL; Mishra-PK; Garcia-Cairasco-N; Dailey-JW; Jobe-PC
ADDRESS OF AUTHOR: Physiology Department, Ribeirao Preto School of Medicine, University of Sao Paulo, Brazil.
SOURCE (BIBLIOGRAPHIC CITATION): Epilepsy-Res. 1994 Feb; 17(2): 157-65
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: NETHERLANDS
ABSTRACT: Substantia nigra (SN) is known to play an important role in seizure generalization. Both excitatory and inhibitory neurotransmitters can modulate this role of SN. Previous studies have shown that GABA as well as aspartate and glutamate participate in seizure regulation through this site. Evidence for such a role comes from studies on the genetically epilepsy-prone rat (GEPR) and other seizure models. In the GEPR, bilateral microinjections of NMDA receptor antagonists in SN block or reduce seizure severity. In order to further evaluate which neurotransmitters are specifically involved at the SN level of seizure regulation in the GEPR, we undertook a microdialysis study of K+ stimulated release of amino acids in the SN of GEPR-9s- and non-epileptic controls. A 1 mm loop-type microdialysis probe was inserted through pre-implanted guides into the SN of awake and freely moving rats (seven GEPR-9s and four non-epileptic controls), and used to perfuse a 100 mM K+ (high K+) solution for 2 h. Four 30 microliters samples were collected prior to high K+ stimulation (basal release), during high K+ perfusion, and after high K+ infusion. After precolumn derivatization with phenylisothiocyanate, levels of aspartic (ASP) and glutamic (GLU) acids, glycine (GLY), taurine (TAU) and GABA were measured by reversed phase high performance liquid chromatography. Two hours after the initiation of high K+ infusion, the increases relative to basal were, for non-epileptic controls, 35%, 74%, 68%, 847% and 283% respectively for ASP, GLU, GLY, TAU and GABA. Corresponding increases for GEPR-9s were 14%, 10%, 41%, 505% and 123% respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
NAME OF SUBSTANCE: Amino-Acids; Taurine; Potassium
Record 12 of 21 in MEDLINE EXPRESS (R) 1993-1995
TITLE: Transmitter amino acid levels in rat brain regions after amygdala-kindling or chronic electrode implantation without kindling: evidence for a pro-kindling effect of prolonged electrode implantation.
AUTHOR(S): Loscher-W; Horstermann-D; Honack-D; Rundfeldt-C; Wahnschaffe-U
ADDRESS OF AUTHOR: Department of Pharmacology, Toxicology, and Pharmacy, School of Veterinary Medicine, Hannover, Germany.
SOURCE (BIBLIOGRAPHIC CITATION): Neurochem-Res. 1993 Jul; 18(7): 775-81
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: Kindling is a chronic model of epilepsy characterized by a progressive increase in response to the same regularly applied stimulus. The biological basis of the kindling phenomenon requires to be determined, but several studies indicate that alterations in amino acidergic neurotransmission may be involved. In the present experiments, levels of glutamate, aspartate, GABA, glycine, and taurine were determined in 12 brain regions by HPLC in 3 groups of animals: (a) a group which was kindled via electrical stimulation of intraamygdala electrodes and was sacrificed 36 days after the last fully kindled seizure for neurochemical determinations; (b) a group of implanted but nonstimulated rats (surgical control group) in which neurochemical measurements were done at the same time after electrode implantation as the kindled group, and (c) a group of non-implanted, naive control rats. Compared to surgical controls, kindling induced a significant reduction of glutamate, GABA, and taurine in the brain stem (pons/medulla), whereas no differences between both groups were found in any of the other regions. However, both electrode-implanted groups differed significantly from non-implanted naive rats in several regions, indicating that electrode-implantation per se induced long-lasting alterations in transmitter amino acids. The most striking difference to naive controls was an increase of glycine levels in several regions in which this amino acid is known to potentiate glutamatergic transmission. In order to examine the functional consequences of prolonged electrode implantation, seizure thresholds were determined in groups of rats with short and prolonged electrode implantation.(ABSTRACT TRUNCATED AT 250 WORDS)
NAME OF SUBSTANCE: Amino-Acids; Glutamates; Neurotransmitters; Taurine; GABA; Glycine; Aspartic-Acid; Glutamic-Acid
Record 13 of 21 in MEDLINE EXPRESS (R) 1993-1995
TITLE: Co-variation of free amino acids in human epileptogenic cortex.
AUTHOR(S): Hamberger-A; Haglid-K; Nystrom-B; Silfvenius-H
ADDRESS OF AUTHOR: Institute of Neurobiology, University of Goteborg, Sweden.
SOURCE (BIBLIOGRAPHIC CITATION): Neurochem-Res. 1993 Apr; 18(4): 519-25
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: The concentration of free amino acids was measured in 41 surgically removed samples of human epileptogenic brain and in 7 specimens of non-epileptic brain tissue, removed during surgery for meningiomas, etc. The material was subdivided according to the neuropathological diagnosis: mild cortical dysplasia (MCD), gliosis astrocytoma infiltration and a histologically heterogeneous group. The non-tumoral epileptogenic samples had five times higher than normal concentration of ethanolamine and 50% elevated concentration of glycine. The concentration of other neurotransmitter amino acids did not differ markedly between epileptogenic and non-epileptic samples. The concentration of neurotransmitter amino acids showed a strong correlation with the enzyme neuron specific enolase (NSE) and were low in most samples with astrocytoma infiltration. On the other hand, tyrosine and leucine had higher concentrations in samples with lower NSE concentration. Factor analysis of the amino acids revealed four groups of covarying compounds in the brain samples, first, a neurotransmitter group, including aspartate, glutamate, GABA and phosphoethanolamine. Another group contained ethanolamine, glutamine, glycine and taurine. Factor analysis on corresponding extracellular amino acids showed two groups, the first being a "neurotransmitter" group, containing serine, taurine phosphoethanolamine and ethanolamine in addition to aspartate and glutamate. The other group consisted of asparagine, glycine, alanine, tyrosine, valine, phenylalanine, isoleucine and leucine.
NAME OF SUBSTANCE: Phosphopyruvate-Hydratase; Amino-Acids; Ethanolamines; Glial-Fibrillary-Acidic-Protein; Nerve-Tissue-Protein-S-100; Neurotransmitters; Ethanolamine; Glycine
Record 14 of 21 in MEDLINE EXPRESS (R) 1993-1995
TITLE: Serum amino acids, liver status, and antiepileptic drug therapy in epilepsy.
AUTHOR(S): Rao-ML; Stefan-H; Scheid-C; Kuttler-AD; Froscher-W
ADDRESS OF AUTHOR: Nervenklinik der Rheinischen Friedrich-Wilhelms-Universitat, Bonn, Germany.
SOURCE (BIBLIOGRAPHIC CITATION): Epilepsia. 1993 Mar-Apr; 34(2): 347-54
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: Serum amino acid (AA) profiles are altered in epilepsy. It is not clear whether this is due to the disease process itself or to other variables such as seizure type, seizure frequency, duration of illness, medication, or altered liver function. We investigated serum AA profiles and liver enzymes in 73 epileptic patients and 90 healthy subjects and evaluated the data by analysis of variance to discriminate between age, sex, seizure type, duration of illness, seizure frequency, antiepileptic drug (AED) and increased serum liver enzyme levels, and their putative interaction with the serum AA profile. There was no correlation between the changes in the AA profile and age, duration of illness, seizure frequency, and seizure type. Seventy-two percent of the AED-treated patients and 33% of the unmedicated patients showed an increase in one or several serum liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and/or gamma-glutamyl transferase (gamma-GT)]; particularly gamma-GT. We observed a significant increase in serum concentrations of glutamine and glycine and decreased levels of taurine, threonine, serine, valine, methionine, isoleucine, leucine, phenylalanine, histidine, tryptophan, and arginine in AED-treated patients but not in unmedicated patients. These results show that the changes in the serum AA profiles of epileptic patients treated with AEDs occur in patients with alteration of serum liver enzymes; whether this implies a causal relation is still uncertain.
NAME OF SUBSTANCE: gamma-Glutamyltransferase; Aspartate-Transaminase; Alanine-Transaminase; Amino-Acids; Anticonvulsants; Carbamazepine; Valproic-Acid
Record 15 of 21 in MEDLINE EXPRESS (R) 1993-1995
TITLE: The involvement of taurine in the action mechanism of sodium valproate (VPA) in the treatment of epilepsy.
AUTHOR(S): Anyanwu-E; Harding-GF
ADDRESS OF AUTHOR: Department of Vision Sciences, Aston University, Aston Triangle, Birmingham, England.
SOURCE (BIBLIOGRAPHIC CITATION): Acta-Physiol-Pharmacol-Ther-Latinoam. 1993; 43(1-2): 20-7
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: ARGENTINA
ABSTRACT: Several lines of evidence have shown that sodium valproate (VPA) mechanism of action in the therapy of epilepsy is based on the phenomena of its interaction with neurotransmitters (GABA), receptor sites and ion channels (1). However, there is no conclusive evidence to show the extent of VPA interactions with other neurotransmitters in the brain. Based on this fact, taurine (an amino acid 'neurotransmitter') found distributed in the brain the visual system may probably be involved in the drug action mechanism of VPA. The application of taurine in experimental and human epilepsy started over thirty years ago (2,3) and it has been known to possess some mild anticonvulsant activity in both humans and experimental animal models (4). This review, therefore, will attempt to draw together all the available information on the involvement of taurine in epilepsy and its possible association with the action mechanism of VPA in suppressing epileptic seizures. Structural and physiological distribution of taurine in the brain will be discussed. Its association with the phenomena of VPA action in epilepsy will be cited. Its neurotransmitter candidacy, involvement in ocular pathology, receptor sites and modulatory activity will be dealt with in relation to valproate action in the therapy of epilepsy.
NAME OF SUBSTANCE: Taurine; Valproic-Acid
Record 16 of 21 in MEDLINE EXPRESS (R) 1993-1995
TITLE: Amino acids in cerebrospinal and brain interstitial fluid in experimental pneumococcal meningitis.
AUTHOR(S): Guerra-Romero-L; Tureen-JH; Fournier-MA; Makrides-V; Tauber-MG
ADDRESS OF AUTHOR: Infectious Diseases Laboratories, San Francisco General Hospital, California.
SOURCE (BIBLIOGRAPHIC CITATION): Pediatr-Res. 1993 May; 33(5): 510-3
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: Excitatory amino acids are increasingly implicated in the pathogenesis of neuronal injury induced by a variety of CNS insults, such as ischemia, trauma, hypoglycemia, and epilepsy. Little is known about the role of amino acids in causing CNS injury in bacterial meningitis. Several amino acids were measured in cerebrospinal fluid and in microdialysis samples from the interstitial fluid of the frontal cortex in a rabbit model of pneumococcal meningitis. Cerebrospinal fluid concentrations of glutamate, aspartate, glycine, taurine, and alanine increased significantly in infected animals. Among the amino acids with known excitatory or inhibitory function, interstitial fluid concentrations of glutamate were significantly elevated (by 470%). Alanine, a marker for anaerobic glycolysis, also increased in the cortex of infected rabbits. The elevated glutamate concentrations in the brain extracellular space suggest that excitotoxic neuronal injury may play a role in bacterial meningitis.
NAME OF SUBSTANCE: Amino-Acids; Glutamates; Glutamic-Acid
Record 17 of 21 in MEDLINE EXPRESS (R) 1993-1995
TITLE: Cerebrospinal fluid levels of neuropeptides, cortisol, and amino acids in patients with epilepsy.
AUTHOR(S): Devinsky-O; Emoto-S; Nadi-NS; Theodore-WH
ADDRESS OF AUTHOR: Clinical Epilepsy Section, NINDS, NIH, Bethesda, Maryland.
SOURCE (BIBLIOGRAPHIC CITATION): Epilepsia. 1993 Mar-Apr; 34(2): 255-61
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: We measured lumbar cerebrospinal fluid (CSF) levels of somatostatin, cholecystokinin, neurotensin, atrial natriuretic factor, vasoactive inhibitory peptide, neuropeptide Y, adrenocorticotrophic hormone, corticotropin releasing hormone, beta-endorphin, metenkephalin, cortisol, alanine, glycine, aspartate, glutamate, taurine, and gamma-aminobutyric acid in 25 inpatients with epilepsy at known interictal and postictal times and in 11 neurologically normal volunteers. There were no significant differences between interictal or postictal complex partial seizures (CPS), postictal generalized tonic-clonic seizures (GTC), and control CSF neuropeptide, cortisol, and amino acid (AA) levels. However, there were nonsignificant trends for CSF levels of several neuropeptides to be increased after CPS and GTC as compared with interictal baseline levels. There were significant correlations between levels of certain CSF neuropeptides or (AAs) and serum antiepileptic drug (AED) levels. Several correlations were noted between CSF levels of AAs, including a correlation between the excitatory neurotransmitters aspartate and glutamate identified only after CPS.
NAME OF SUBSTANCE: Amino-Acids; Glutamates; Neuropeptides; Hydrocortisone; GABA; Aspartic-Acid; Glutamic-Acid
Record 18 of 21 in MEDLINE EXPRESS (R) 1993-1995
TITLE: 1H magnetic resonance spectroscopy of extracts of human epileptic neocortex and hippocampus.
AUTHOR(S): Peeling-J; Sutherland-G
ADDRESS OF AUTHOR: Department of Chemistry, University of Winnipeg, Manitoba, Canada.
SOURCE (BIBLIOGRAPHIC CITATION): Neurology. 1993 Mar; 43(3 Pt 1): 589-94
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: We used high-resolution 1H magnetic resonance spectroscopy to determine the concentrations of several metabolites (lactate, alanine, N-acetylaspartate [NAA], gamma-aminobutyrate, glutamate, aspartate, creatine, cholines, taurine, inositol, and succinate) in tissue from patients undergoing surgical treatment of intractable epilepsy, and correlated the metabolite profiles with the results of histopathologic analysis of the excised tissue. We found no differences in metabolite levels for tissue from actively spiking or nonspiking neocortical sites in temporal lobe epilepsy patients. In neocortical tissue from patients with chronic localized encephalitis (Rasmussen's encephalitis), the metabolite concentrations varied with the severity and extent of the encephalitis. In tissue showing mild encephalitis and mild histologic abnormalities, the metabolite levels differed little from those found for nonencephalitic neocortical tissue. Tissue showing marked abnormalities and extensive encephalitis had decreased NAA, glutamate, cholines, and inositol. In hippocampal tissue from temporal lobe epilepsy patients, the levels of NAA, glutamate, and aspartate were lower and the levels of alanine, taurine, and inositol were higher than in neocortical tissue from the same patients. The decrease in the levels of NAA and glutamate was greater in gliotic hippocampal tissue. The results suggest that in vivo 1H magnetic resonance spectroscopy may aid in diagnosing the extent of chronic localized encephalitis and the severity of hippocampal gliosis.
NAME OF SUBSTANCE: Amino-Acids; Glutamates; GABA; Aspartic-Acid; Glutamic-Acid; N-acetylaspartate
Record 19 of 21 in MEDLINE EXPRESS (R) 1993-1995
TITLE: A multiparametric data analysis showing the potential of localized proton MR spectroscopy of the brain in the metabolic characterization of neurological diseases.
AUTHOR(S): Confort-Gouny-S; Vion-Dury-J; Nicoli-F; Dano-P; Donnet-A; Grazziani-N; Gastaut-JL; Grisoli-F; Cozzone-PJ
ADDRESS OF AUTHOR: Centre de Resonance Magnetique Biologique et Medicale, URA-CNRS 1186, Faculte de Medecine, Marseille, France.
SOURCE (BIBLIOGRAPHIC CITATION): J-Neurol-Sci. 1993 Sep; 118(2): 123-33
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: NETHERLANDS
ABSTRACT: We conducted an extended clinical evaluation of localized proton magnetic resonance spectroscopy (MRS) of the brain, performed on various brain diseases using short stimulated echo times. Pathologies studied were mainly multiple sclerosis, stroke, leukoaraiosis, AIDS-related leukoencephalopathies and glial tumors. Other miscellaneous pathologies were also studied. Magnetic resonance examination of the brain was conducted on a Siemens Magnetom SP63 (equipped with a 1.5 T magnet). Localized proton MRS was performed on a routine basis immediately after imaging, using the STEAM (stimulated echo acquisition mode) with a short echo time (20 ms) combined with a CHESS (chemical shift selective excitation) sequence. One or two VOI (8 ml) were examined. Data on 125 spectra were processed by principal component analysis (PCA) and conventional variance analysis. The following metabolite resonances were studied: inositol-glycine, taurine-scyllo-inositol, choline derivatives, phosphocreatine-creatine, aspartate, glutamine glutamate, N-acetylaspartate, acetate and lactate. PCA demonstrates that the different metabolic variables are independent. The analysis of groups of spectra clearly demonstrates that the metabolic profiles detected by localized MRS in various pathologies (i) differ significantly from controls, and (ii) allow a metabolic discrimination between groups of pathologies. Results of PCA are confirmed by variance analysis. Strokes are characterized by an increase in lactate concentration and leukoaraiosis by a decrease in inositol-glycine resonance. AIDS-related leukodystrophies are characterized by increases in lactate and choline concentrations. Reduction in N-acetylaspartate which is observed in most pathologies is not significant in the small lesions of white matter. Lactate has often been found in MS plaques, but no variation in the choline/phosphocreatine ratio was observed. GABA was tentatively assigned in the spectrum of a patient with epilepsy under sodium valproate treatment. This study illustrates the clinical feasibility of the technique, the value of a multiparametric data analysis in the definition of the pertinent variables characterizing the metabolic impairment, and the impact of localized proton MR spectroscopy of the brain in the assessment of cerebral suffering.
Record 20 of 21 in MEDLINE EXPRESS (R) 1993-1995
TITLE: Alteration of amino acid in plasma and cerebrospinal fluid of children with seizure disorders.
AUTHOR(S): Ko-FJ; Chiang-CH; Liu-WJ; Chiang-W
ADDRESS OF AUTHOR: Department of Pediatrics, Kaohsiung Medical College, Taiwan, Republic of China.
SOURCE (BIBLIOGRAPHIC CITATION): Kao-Hsiung-I-Hsueh-Ko-Hsueh-Tsa-Chih. 1993 Mar; 9(3): 131-42
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: TAIWAN
ABSTRACT: Amino acid levels in plasma were measured by amino acid autoanalyser in 130 convulsive children. The levels of taurine, serine and tryptophan were significantly lower in convulsive children as compared to normal control; in contrast, isoleucine, homocystine, GABA, histidine, arginine and ammonia were higher. The children with paroxysmal disorders (headache, dizziness and abdominal epilepsy) had the highest levels of isoleucine, histidine and arginine and the lowest levels of glutamate and cystein. Clinical seizure activity within 6 months prior to the test seemed to have no obvious effect on the plasma amino acid pattern, except for the levels of glycine and arginine tended to return to normal, and the level of GABA was significantly increased in patients with the seizure being controlled. The patients treated with carbamazepin as a single anticonvulsant had the highest GABA level compared to those with other anticonvulsants. Hyperglycinemia and hyperammonaemia were also noted in patients who took valproic acid. The levels of serine, isoleucine and phenylalanine in the CSF within 6 hours after convulsion were significantly lower than the normal control; while asparagine, tyrosine, lysine and arginine were significantly higher. The concentration of ammonia in the CSF was also elevated after convulsion as compared to the normal control. Amino acids play an important role in the generation of epilepsy and recently there has been an increasing number of studies to help determine their effects during an epileptic attack. However, there still is much debate and controversy on this topic. Therefore, further studies are needed and researchers should carefully consider factors that might affect the accurate assessment of the results.
NAME OF SUBSTANCE: Amino-Acids; Anticonvulsants; GABA
Record 21 of 21 in MEDLINE EXPRESS (R) 1993-1995
TITLE: Effect of sustained pyridoxine treatment on seizure susceptibility and regional brain amino acid levels in genetically epilepsy-prone BALB/c mice.
AUTHOR(S): Dolina-S; Peeling-J; Sutherland-G; Pillay-N; Greenberg-A
ADDRESS OF AUTHOR: Manitoba Institute of Cell Biology, Winnipeg, Canada.
SOURCE (BIBLIOGRAPHIC CITATION): Epilepsia. 1993 Jan-Feb; 34(1): 33-42
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: Epilepsy-prone and epilepsy-resistant substrains were selectively bred from a strain of BALB/c mice; audiogenic-sensitive epilepsy-prone animals showed enhanced sensitivity to chemical convulsants. Treatment with pyridoxine (100 mg/L in drinking water) initiated at mating and continued throughout pregnancy and the life of the offspring abolished the enhanced sensitivity to chemical convulsants and reduced the severity of audiogenic seizures. Withdrawal of pyridoxine restored the enhanced seizure sensitivity. [1H] Nuclear magnetic resonance (NMR) spectroscopy of perchloric acid extracts of tissue was used to determine the concentrations of several compounds [N-acetylaspartate (NAA), GABA, glutamate, aspartate, alanine, taurine, creatine, cholines, inositol] in the hippocampus, neocortex, brainstem, and cerebellum of untreated and pyridoxine-treated 6-week-old female animals. The ratios of the concentrations of excitatory to inhibitory putative neurotransmitter amino acids tended to be higher in epilepsy-prone animals, with the most pronounced difference being a significantly elevated glutamate/GABA ratio in every brain region examined. Pyridoxine treatment abolished this imbalance in the hippocampus, brainstem, and cerebellum, but not in the neocortex. Treatment of epilepsy-resistant animals with pyridoxine using the same protocol decreased the glutamate/GABA concentration ratio in the hippocampus, brainstem, and neocortex and resulted in impaired development of the animals. The amino acid imbalance and the accompanying seizure susceptibility in these genetically epilepsy prone mice may originate from an inborn error in pyridoxine metabolism or in a pyridoxine-dependent enzyme system.
NAME OF SUBSTANCE: Amino-Acids; Pyridoxine