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T N Ferraro

Publications and source records attributed to T N Ferraro.

52 records · Page 3Linked to original sources
PubMed1989

Chronic lithium treatment and status epilepticus induced by lithium and pilocarpine cause selective changes of amino acid concentrations in rat brain regions.

We measured the effects of four weeks of dietary lithium treatment and of status epilepticus induced by administration of pilocarpine to lithium-treated rats on the concentrations of amino acids in four regions of rat brain: cerebral cortex, hippocampus, striatum, and substantia nigra. To ensure accurate quantitation of the amino acids, animals were sacrificed by focussed beam microwave irradiation and amino acids were measured using a fully validated triple-column ion-exchanged amino acid analyzer with post-column o-phthalaldehyde derivatization and fluorometric detection. The concentrations of four amino acids, threonine, methionine, lysine and tyrosine, were increased significantly in two to four brain regions by chronic lithium treatment. Their concentrations remained elevated, or were further increased, during status epilepticus. The concentrations of eight amino acids and ammonia were not altered by lithium treatment but increased in concentration during status epilepticus in some brain regions. Glycine, serine, arginine and citrulline were decreased by chronic lithium treatment. Status epilepticus increased the concentrations of these four amino acids above that found in the lithium-treated samples in some of the brain regions that were examined. Six amino acids and glutathione were generally unaltered by both treatments. These results are related to the effects of lithium treatment and are compared with changes reported by others following treatment with a variety of convulsive stimuli.

Amino Acids↗
PubMed1989

Amino acid profiles in Long-Evans rat superior colliculus, visual cortex, and inferior colliculus.

An ultrasensitive triple-column ion-exchange/fluorometric method was utilized to measure the levels of over 30 amino acids and related primary amino compounds in Long-Evans rat superior colliculus (SC), visual cortex (VC) and inferior colliculus (IC). Comparison of levels of amino compounds revealed distinctly different profiles for each region. Major constituents were the neurotransmitters and related compounds glutamate, glutamine, GABA, taurine, aspartate and glycine. Glutathione levels were also relatively high in all three regions. SC exhibited a significantly higher level of GABA and beta-alanine compared to both VC and IC. VC had significantly higher levels of glutamate and taurine. VC exhibited the lowest level of glycine and IC the highest. A time-course experiment using SC documented that levels of eleven of thirty-four compounds, including GABA, were subject to significant postmortem alteration in vitro. SC GABA stability experiments indicated that significant in vitro increases of free GABA levels between 1 and 4 min postmortem were associated with equimolar decreases of conjugated GABA levels.

Amino Acids↗
PubMed1988

Cerebrospinal fluid amino compounds in Parkinson's disease. Alterations due to carbidopa/levodopa.

Employing a triple-column ion-exchange/fluorometric procedure, 29 amino compounds, including amino acid neurotransmitters, were measured in lumbar cerebrospinal fluid (CSF) from two groups of patients with idiopathic Parkinson's disease de novo (n = 6) and those who were treated with carbidopa/levodopa (n = 6), and from neurologically normal controls (n = 10). Consideration was given to in vivo and in vitro factors known to influence levels of various CSF constituents. Results showed statistically significant decreases in the levels of gamma-aminobutyric acid, homocarnosine, phosphoethanolamine, and threonine, and elevation of ornithine levels, in the CSF of de novo patients with Parkinson's disease compared with controls. These changes "normalized" following treatment with carbidopa/levodopa. This study suggests that Parkinson's disease may be characterized by defects in specific amino compound metabolic pathways, resulting in central nervous system amino compound imbalances that may contribute to the pathophysiology of this disorder. Carbidopa/levodopa therapy tends to "normalize" these amino compound imbalances.

Adult↗
PubMed1988

Cerebral metabolism of parkinsonian primates 21 days after MPTP.

This study evaluates the changes in the local cerebral metabolic rate for glucose (LCMRg) in primates exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The LCMRg was evaluated 21 days following the last dose of MPTP. At this time, all MPTP-injected animals demonstrated parkinsonism and striatal dopamine was reduced to less than 3% of control values. The structures whose LCMRg was most affected were the motor cortex, the intermediate zone of the putamen, the external segment of the globus pallidus, the medial part of the ventrolateral nucleus of the thalamus (VLm), visual cortex, locus ceruleus, and the dorsolateral segment of the substantia nigra pars compacta. The structure whose increase in LCMRg correlated most closely to the clinical severity of parkinsonism was the external segment of the globus pallidus.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1988

Systemic acetyl-L-carnitine elevates nigral levels of glutathione and GABA.

Amino acid and reduced glutathione (GSH) levels in substantia nigra (SN) as well as striatal monoamine levels were measured in acetyl-L-carnitine (ALCar) treated and control Swiss-Webster mice. ALCar, L carnitine, or saline were administered i.p. to mice for 5 days and mice were decapitated 24 hours following the last injection. Substantia nigra and striata were isolated within 2.5 and 3 min., respectively, and frozen immediately on dry ice. A significant dose-dependent increase of nigral GABA was observed following ALCar treatment; GABA levels were also increased by administration of carnitine. Nigral GSH levels were also increased. Striatal levels of dopamine and metabolites were not significantly affected by ALCar or carnitine. These results, suggest that ALCar may be useful in treating symptoms of neuronal dysfunction related to accumulation of metabolic waste.

Acetylcarnitine↗
PubMed1987

MPTP and convulsive responses in rodents.

Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg/kg s.c. for 5 days) to mice resulted in complete abolishment of strychnine seizure and of the tonic phase of the maximal electroshock response. Bicuculline and picrotoxin convulsions were not significantly affected by MPTP treatment. The severity of the pentylenetetrazole seizures was mildly, but significantly affected in the protective way. MPTP depleted neostriatal dopamine and its metabolites, together with hippocampal norepinephrine. No nigral neuronal loss was detected histologically. Strychnine seizures and the tonic phase of the maximal electroshock response are thought to depend mostly on hindbrain (bulbo-spinal) structures. Thus, these experiments suggest that a caudally projecting system originates from the substantia nigra, pars compacta, and/or locus coeruleus, controlling seizures that involve bulbo-spinal centers. While neostriatal dopamine depletion offers a good index of seizure resistance, its role in the protection from seizures remains to be established.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Isoniazid-induced alteration of CSF neurotransmitter amino acids in Huntington's disease.

During a randomized, double-blind, crossover, placebo-controlled clinical trial of isoniazid (plus pyridoxine) in Huntington's disease (HD), amino acids and related amino compounds were measured in both cerebrospinal fluid (CSF) and plasma utilizing a newly developed high-performance liquid chromatography ion-exchange/fluorometric assay method. Results showed that isoniazid (plus pyridoxine) significantly elevated the mean (+/- S.E.M.) levels of gamma-aminobutyric acid, aspartate, asparagine, homocarnosine, ornithine, histidine, alpha-aminobutyric acid, isoleucine, leucine and alanine in CSF and the levels of beta-alanine in both CSF and plasma. These alterations can be traced to inhibition of decarboxylation and transamination reactions requiring the cofactor pyridoxal phosphate and may be related to the observed equivocal clinical response in the HD patients. The differential influence of isoniazid on plasma and CSF amino acid profiles suggests that alterations of CNS amino acid metabolism may be reflected in CSF, and that isoniazid-induced alterations of amino acid metabolism in the CNS differ from those in the periphery.

Adult↗
PubMed1987

Brain gamma-aminobutyric acid abnormality in tardive dyskinesia. Reduction in cerebrospinal fluid GABA levels and therapeutic response to GABA agonist treatment.

A double-blind, placebo-controlled trial of gamma-vinyl gamma-aminobutyric acid (GVG) and 4,5,6,7-tetrahydroisoxazolo-(5,4-c) pyridine-3-ol (THIP) was carried out in drug-free schizophrenic patients with tardive dyskinesia. A significant decrease in dyskinetic symptoms occurred with the administration of GVG, associated with a twofold increase in cerebrospinal fluid levels of GABA; THIP produced a more moderate, yet consistent decrease in the involuntary movements. A pathophysiologic role for gamma-aminobutyric acid (GABA)-mediated neuronal transmission in tardive dyskinesia was explored by analyzing cerebrospinal fluid GABA concentrations in drug-free schizophrenic patients with and without tardive dyskinesia. A significant reduction in cerebrospinal fluid levels of GABA was observed in the dyskinetic schizophrenics compared with the nondyskinetic controls. These data compliment a growing body of experimental evidence suggesting a critical role for GABA-ergic neurons in the pathophysiology of tardive dyskinesia.

Adult↗
PubMed1986

Effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on levels of glutathione in the extrapyramidal system of the mouse.

Treatment of mice with the proximate neurotoxin MPTP depletes striatal dopamine levels. Depletion of striatal dopamine and metabolites in MPTP-treated mice is accompanied by depletion of glutathione (GSH) in the substantia nigra (SN). Striatal GSH and nigral amino acid levels were not significantly affected by MPTP. Results suggest that GSH depletion in SN may represent an index of regional vulnerability to metabolic oxidative stress and also of selective susceptibility to the toxic effects of MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

Free and conjugated amino acids in human CSF: influence of age and sex.

An extended baseline characterization of amino acids (AAs) and related amino compounds in CSF is reported. Thirty-one amino compounds were measured in deproteinized CSF before and after acid hydrolysis using a triple-column HPLC/fluorometric analyzer. CSF specimens were collected under strictly controlled conditions from neurologically normal myelogram patients and carefully pooled with regard to subject age and sex. Consideration was given to factors which may produce artifactual alterations in AA levels during CSF collection, storage and handling. Conjugated AAs were determined as the difference between levels of free AAs (measured in CSF prior to hydrolysis) and total AAs (measured in hydrolyzed CSF) and are taken as an index of total CSF peptide AAs. Results documented conjugated forms of all non-acid-labile CSF AAs except citrulline and ethanolamine. In general, ratios of conjugated to free AAs were relatively low, however for the neurotransmitter AAs aspartate, glutamate, glycine and GABA as well as for beta-alanine hydrolysis produced marked increases indicating that these compounds are present predominantly in bound form in CSF. Results also revealed the significant influence of both age and sex on levels of a number of CSF free and conjugated AAs. Compared to younger individuals (those less than 40 years of age), older individuals exhibited significantly higher levels of free aspartate, glycine, alpha-aminobutyric acid, valine, isoleucine, leucine, phenylalanine and 3-methylhistidine as well as significantly lower levels of free phosphoethanolamine, serine, GABA, homocarnosine, conjugated GABA and conjugated beta-alanine. Additionally, significantly higher levels of free tyrosine, ethanolamine, arginine and conjugated aspartate were documented in males compared to females.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Triple-column ion-exchange physiological amino acid analysis with fluorescent detection: baseline characterization of human cerebrospinal fluid.

A highly resolving triple-column amino acid analyzer with fluorometric detection is described. The reliability of this technique was evaluated and it was used in a baseline investigation of amino acids and related compounds in human cerebrospinal fluid (CSF). The procedure employs three distinct ion-exchange columns to elute the acidic, neutral, and basic amino acids, respectively. Each column is run isocratically with lithium citrate buffers designed to provide overlapping elution profiles. Studies using CSF collected under strictly controlled conditions documented nanomolar concentrations of aspartate, gamma-aminobutyric acid (GABA), beta-alanine, 1-methylhistidine, and 3-methylhistidine, as well as low levels of glutamate, methyllysine, and ammonia. In addition, other common amino acids were also quantified. Chromatograms of CSF from all three systems (acidic, neutral, and basic) exhibited numerous uncharacterized compounds emphasizing the resolution and sensitivity of the analytical procedure. In vitro stability studies revealed that levels of aspartate, glutamate, GABA, homocarnosine, and ammonia are subject to significant change when CSF is maintained at room temperature for various periods of time up to 24 h. It is concluded that the valid and accurate measurement of CSF amino compounds, especially the neurotransmitter amino acids, requires a highly specific and sensitive assay procedure as well as strict control of CSF manipulation in vitro.

Amino Acids↗
PubMed1983

Further characterization of in vitro conditions appropriate for GABA determination in human CSF: impact of acid deproteinization and freeze/thaw.

Recently established standardized protocols for collection, handling, and storage of CSF for measurement of gamma-aminobutyric acid (GABA) have proven valuable in the characterization of various CNS disorders. In response to two recent reports which may have an impact on certain widely used protocols, we have, using the confirmed ion-exchange/fluorometric procedure, systematically evaluated the effects of deproteinization with various concentrations of sulfosalicylic acid (SSA) ranging from 0 to 10% (100 mg/ml), as well as the effects of freeze/thaw (F/T) on CSF GABA levels. Results of F/T studies documented that levels are stable to freezing and thawing. Acid deproteinization studies revealed the presence of an equilibrium between strictly free GABA, demonstrable only in acid-free CSF, and a very loosely bound form of GABA, fully demonstrable only in CSF deproteinized with concentrations of SSA above 1% (10 mg/ml). The relationship between GABA concentrations in undeproteinized and acid-deproteinized CSF revealed a highly significant (p less than .001) correlation, suggesting that alterations of central GABAergic activity would be reflected by either the level of strictly free GABA or free plus loosely bound GABA. This hypothesis was upheld in studies of patients with Parkinson's disease (PD) and Huntington's disease (HD), two neurologic disorders in which dysfunctions of the GABA system have been implicated. Results indicated that CSF GABA levels are significantly reduced in both PD and HD patients compared with neurologically normal controls, whether the measurement is of free GABA or free plus loosely bound GABA. Thus, we conclude that the level of strictly free GABA is stable to freezing and thawing and can only be accurately determined in nonacidified CSF; however, existing protocols employing deproteinization in 5% SSA yield data that provide an equally good reflection of central GABAergic transmission.

Adult↗
PubMedDate not supplied

Continuous monitoring of brain ethanol levels by intracerebral microdialysis.

A method is described which allows simultaneous collection of blood and perfusate of discrete brain regions from an individual animal over several hours. This procedure involves catheterization of a peripheral blood vessel (jugular vein) and the insertion of a microdialysis probe into a specified brain area (lateral hypothalamus) for sampling of blood and brain perfusate, respectively. Using this procedure, levels of ethanol in blood and brain perfusates were determined by scintillation counting following administration of [14C]-ethanol (20 mu Ci) to adult male rats at a dose of 0.8 or 2.4 g/kg. Ethanol levels in brain and blood as well as the time-course of disappearance were dependent on the dose administered. Peak blood levels were observed in the first sample taken (i.e., at 10 min), whereas a slight delay was noted in the time to peak level in brain. At subsequent time points, a good correlation was observed between blood and brain perfusate radioactivity levels although perfusate levels were slightly lower. It is concluded that this approach will prove useful for investigating the molecular and cellular mechanisms of action of ethanol by enabling the direct correlation of blood and brain ethanol levels with various behavioral, electrophysiological and/or biochemical measures.

Animals↗