Convulsions and the γ-aminobutyric acid content of rat brain

1968 ◽  
Vol 46 (5) ◽  
pp. 803-804 ◽  
Author(s):  
F. V. DeFeudis ◽  
K. A. C. Elliott
Keyword(s):  
High Pressure ◽  
Rat Brain ◽  
Acid Content ◽  
Aminobutyric Acid ◽  
The Brain

The observation of Wood and Watson that the γ-aminobutyric acid content of the brain decreases in animals that suffer convulsions during treatment with oxygen at high pressure has been confirmed. This decrease is prevented when seizures are prevented by prior intraperitoneal injections of hyperosmotic solutions. When seizures are induced by picrotoxin or pentylenetetrazol the GABA levels are slightly (and alanine levels considerably) increased.

Effect of adrenalectomy on convulsions induced by high-pressure oxygen

1979 ◽  
Vol 57 (7) ◽  
pp. 688-694 ◽  
Author(s):  
A. K. Singh ◽  
E. W. Banister
Keyword(s):  
High Pressure ◽  
Acid Level ◽  
Amino Acid Level ◽  
Aminobutyric Acid ◽  
Pressure Oxygen ◽  
Significant Difference ◽  
High Pressure Oxygen ◽  
Brain Gaba ◽  
The Brain ◽  
Adrenalectomized Rats

Adrenalectomized rats exposed to high pressure oxygen (OHP) until convulsion convulse much later than sham-operated or normal rats. No significant changes in the concentration of noradrenaline (NA) and total catecholamines (TC) in the brain were noted in sham-operated or adrenalectomized rats resulting from sham or real surgery and no change occurred in these variables in normal sham-operated or adrenalectomized animals after OHP leading to convulsion. Brain adrenaline (A) concentration, however, decreased significantly in all three groups following OHP-induced convulsions. Activity of catecholamine O-methyltransferase (COMT) decreased significantly only in adrenalectomized rats. Brain γ-aminobutyric acid (GABA), glutamate, and other amino acid level remained unchanged after adrenalectomy whereas the concentration of ammonia decreased significantly when normal rats were adrenalectomized. After OHP-induced convulsions, the concentrations of brain GABA and glutamate decreased and ammonia and glutamine plus asparagine increased significantly in normal, sham-operated, and adrenalectomized rats. In the blood no significant difference was noted in the concentration of the catecholamines, ammonia, and amino acids either in normal or sham-operated rats. In adrenalectomized rats, the blood A and NA concentrations decreased significantly and tyrosine increased significantly. The concentration of NA, ammonia, and glutamine plus asparagine in rats from all three groups increased after OHP-induced convulsions, whereas the concentration of glutamate decreased significantly. Since the concentration of A increased significantly after convulsions in normal and sham-operated rats but did not change in adrenalectomized rats, it might be proposed that adrenalectomy protects against OHP-induced convulsions by reducing the circulating concentration of A and ammonia.However, these are not the only factors involved in the protection since the sham-operated rats also convulsed much later than normal rats but had similar ammonia and A concentrations to normal animals.

scholarly journals Increase in the γ-Aminobutyric Acid Content of Rat Brain After Ingestion of Ethanol

Nature ◽  
1959 ◽  
Vol 184 (4687) ◽  
pp. 726-726 ◽  
Author(s):  
H-M. HÄKKINEN ◽  
E. KULONEN
Keyword(s):  
Rat Brain ◽  
Acid Content ◽  
Aminobutyric Acid

Effects of hexamethonium and methyl-p-tyrosine on normal rats subjected to convulsions induced by oxygen at high pressure

1980 ◽  
Vol 58 (3) ◽  
pp. 237-242 ◽  
Author(s):  
E. W. Banister ◽  
A. K. Singh
Keyword(s):  
Amino Acids ◽  
High Pressure ◽  
Protective Action ◽  
Latency Period ◽  
Oxygen Toxicity ◽  
Aminobutyric Acid ◽  
Brain Catecholamines ◽  
Oxidative Deamination ◽  
The Brain ◽  
Catecholamine Concentration

Hexamethonium infusion (intravenous) does not alter the concentrations of brain catecholamines, ammonia, and amino acids in rats under normal conditions. However, it decreases the concentration of blood adrenaline (A) and nonadrenaline (NA) significantly without affecting blood ammonia and amino acids. Injection of α-methyl-p-tyrosine (α-MPT) (intraperitoneal) decreases brain catecholamines without affecting the concentration of ammonia and amino acids in the brain or catecholamines, ammonia, and amino acids in the blood.In normal, hexamethonium-, and α-MFT-treated rats convulsed by exposure to oxygen at high pressure (OHP), the concentration of ammonia and glutamine plus aspargine increased and glutamate and γ-aminobutyric acid (GABA) (brain only) decreased significantly in both blood and brain. After convulsion, hexamethonium and α-MPT effect the same degree of concentration change for ammonia and amino acids in both blood and brain.When hexamethonium-treated rats are convulsed by OHP, the concentrations of A and NA in blood increased significantly. However, the postconvulsive concentration of A in these rats is significantly less than the preconvulsive control values of normal, undrugged rats. Hexamethonium also prolongs the latency period before convulsions induced by exposure of rats to OHP. This protective action of hexamethonium against oxygen toxicity is probably due to (a) some direct effect of low circulating catecholamines, or (b) delay in the production of toxic levels of ammonia from oxidative deamination of catecholamines, as initial low catecholamine concentration would hinder accumulation of ammonia from such deamination.α-MPT treatment was ineffective in producing an increased latency period before convulsion occurred despite the prevailing low brain catecholamine initially produced by α-MPT treatment. However, the concentration of brain A, NA, and total catecholamines decreased significantly after α-MPT-treated rats were convulsed by OHP exposure. The response of blood catecholamines to OHP-induced convulsions in these α-MPT-treated rats is the same as in normal rats.As α-MPT blocks the synthesis of catecholamines, a further decrease in brain catecholamine values after oxygen-induced convulsions in drugged animals suggests that brain catecholamines are oxidatively deaminated to produce ammonia. These observations suggest that, contrary to earlier reports, brain catecholamines do play an important role in producing ammonia during oxygen toxicity, which, in turn, induces convulsions.

DELAY OR INHIBITION OF CONVULSIONS BY INTRAPERITONEAL INJECTIONS OF DIVERSE SUBSTANCES

1967 ◽  
Vol 45 (5) ◽  
pp. 857-865 ◽  
Author(s):  
F. V. DeFeudis ◽  
K. A. C. Elliott
Keyword(s):  
Amino Acids ◽  
High Pressure ◽  
Sodium Chloride ◽  
Chloride Solution ◽  
Sodium Chloride Solution ◽  
Strong Solutions ◽  
Aminobutyric Acid ◽  
Plain Water ◽  
Effective Protection ◽  
The Brain

Prior intraperitoneal injections, into mice or rats, of strong solutions of γ-aminobutyric acid, DL-alanine, other amino acids, succinate, or sucrose tend to postpone or prevent convulsions and death caused by the administration of oxygen at high pressure, picrotoxin, or pentylenetetrazol. Sodium chloride solution was not as consistently effective. Protection against strychnine was not obvious. Injections of urea solutions or plain water were not effective. Intraperitoneal injections of the "protective" solutions cause increased osmolarity of the serum and dehydration of the brain; the latter effect may be partly responsible for the elevation of seizure thresholds.

The Anticonvulsant Properties of Isonicotinic Acid Hydrazide and Associated Changes in γ-Aminobutyric Acid Metabolism

1973 ◽  
Vol 51 (12) ◽  
pp. 959-965 ◽  
Author(s):  
J. D. Wood ◽  
S. J. Peesker
Keyword(s):  
High Pressure ◽  
Acid Metabolism ◽  
Isonicotinic Acid ◽  
Acid Hydrazide ◽  
Aminobutyric Acid ◽  
Isonicotinic Acid Hydrazide ◽  
Acid Decarboxylase ◽  
Anticonvulsant Action ◽  
Drug Mixture ◽  
The Brain

The administration of isonicotinic acid hydrazide and pyridoxine to chicks prior to their being exposed to oxygen at high pressure brought about a delay in the onset of the hyperbaric-oxygen-induced seizures in the birds. The hydrazide was the active anticonvulsant component of the drug mixture but pyridoxine was necessary to prevent seizures induced by the hydrazide itself shortly after its administration. The anticonvulsant action of the drug mixture developed relatively slowly but lasted for several hours and correlated well with concomitant changes in the concentration of γ-aminobutyric acid (GABA) in the brain. No similar correlation was observed between the anticonvulsant action and the activity of either glutamic acid decarboxylase or GABA-α-oxoglutarate aminotransferase.

GAMMA-AMINOBUTYRIC ACID LEVELS IN THE BRAIN OF RATS EXPOSED TO OXYGEN AT HIGH PRESSURES

1963 ◽  
Vol 41 (9) ◽  
pp. 1907-1913 ◽  
Author(s):  
J. D. Wood ◽  
W. J. Watson
Keyword(s):  
High Pressure ◽  
Recovery Time ◽  
High Pressures ◽  
No Reduction ◽  
Ambient Pressure ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Gaba Concentration ◽  
Short Period ◽  
The Brain

Rats were exposed to 100% oxygen at a pressure of 6 atmospheres absolute for 33 minutes. The surviving animals were assigned to one of three groups: (a) animals suffering severe convulsions during exposure, (b) animals suffering mild convulsions during exposure, (c) animals in which no convulsions were observed during exposure. The concentration of gamma-aminobutyric acid (GABA) in the brains of rats in all groups was lower than in unexposed rats, reductions of 35%, 27%, and 19% in GABA concentration being observed in groups (a), (b), and (c) respectively. Only a few minutes' exposure to oxygen at high pressure was necessary to cause a significant decrease in GABA concentration. Exposure either to air at high pressure or to 100% oxygen at ambient pressure produced no reduction in GABA levels. Although the GABA concentration in the brain increased markedly within 1 hour after the end of the 33-minute exposure to oxygen at 6 atm pressure it was still somewhat below the levels found in unexposed animals. No significant change in GABA levels was observed during a further 2 hours of recovery time. In the case of rats exposed for only a short period of time, however, a complete return to normal was observed within the first hour. The levels of glutamic acid, aspartic acid, and total α-amino acids in the brain were not altered by exposure to oxygen at high pressure.

GAMMA-AMINOBUTYRIC ACID LEVELS IN THE BRAIN OF RATS EXPOSED TO OXYGEN AT HIGH PRESSURES

1963 ◽  
Vol 41 (1) ◽  
pp. 1907-1913 ◽  
Author(s):  
J. D. Wood ◽  
W. J. Watson
Keyword(s):  
High Pressure ◽  
Recovery Time ◽  
High Pressures ◽  
No Reduction ◽  
Ambient Pressure ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Gaba Concentration ◽  
Short Period ◽  
The Brain

Rats were exposed to 100% oxygen at a pressure of 6 atmospheres absolute for 33 minutes. The surviving animals were assigned to one of three groups: (a) animals suffering severe convulsions during exposure, (b) animals suffering mild convulsions during exposure, (c) animals in which no convulsions were observed during exposure. The concentration of gamma-aminobutyric acid (GABA) in the brains of rats in all groups was lower than in unexposed rats, reductions of 35%, 27%, and 19% in GABA concentration being observed in groups (a), (b), and (c) respectively. Only a few minutes' exposure to oxygen at high pressure was necessary to cause a significant decrease in GABA concentration. Exposure either to air at high pressure or to 100% oxygen at ambient pressure produced no reduction in GABA levels. Although the GABA concentration in the brain increased markedly within 1 hour after the end of the 33-minute exposure to oxygen at 6 atm pressure it was still somewhat below the levels found in unexposed animals. No significant change in GABA levels was observed during a further 2 hours of recovery time. In the case of rats exposed for only a short period of time, however, a complete return to normal was observed within the first hour. The levels of glutamic acid, aspartic acid, and total α-amino acids in the brain were not altered by exposure to oxygen at high pressure.

The effect of hyperbaric oxygen on the GABA shunt pathway in brain homogenates

1968 ◽  
Vol 46 (4) ◽  
pp. 669-671 ◽  
Author(s):  
W. S. Myles ◽  
J. D. Wood
Keyword(s):  
High Pressure ◽  
Rat Brain ◽  
Ambient Pressure ◽  
Aminobutyric Acid ◽  
Gaba Shunt ◽  
In Vitro Method ◽  
Shunt Pathway ◽  
Effect Of Oxygen ◽  
Small Inhibition

The effect of oxygen at high pressure (OHP) on the γ-aminobutyric acid (GABA) shunt pathway in rat brain homogenates was studied by measuring the formation of labelled succinate from GABA-4-14C in the presence of malonate. Under in vitro conditions, OHP inhibited the GABA shunt by 28% and 22%, with and without the addition of supplementary amounts of GABA and α-ketoglutarate to the incubation media respectively. A small inhibition (10%) was also observed with oxygen at ambient pressure. In further studies, rats were exposed to OHP, and the activity of the GABA shunt in the brains was subsequently measured by the in vitro method. Preexposure of the intact animals, with or without accompanying convulsions, did not affect the metabolism of GABA to succinate.

scholarly journals Cytochrome P450 2D Catalyze Steroid 21-Hydroxylation in the Brain

Endocrinology ◽  
2004 ◽  
Vol 145 (2) ◽  
pp. 699-705 ◽  
Author(s):  
Wataru Kishimoto ◽  
Toyoko Hiroi ◽  
Masakazu Shiraishi ◽  
Mayuko Osada ◽  
Susumu Imaoka ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Rat Brain ◽  
Aminobutyric Acid ◽  
Specific Chemical ◽  
Protein Levels ◽  
Receptor Modulator ◽  
Ic50 Value ◽  
Brain Microsomes ◽  
The Brain ◽  
Hydroxylation Activity

Abstract mRNA of cytochrome P450 21-hydroxylase (P450c21) is expressed in the brain, but little is known about the enzymatic properties of P450c21 in the brain. In the present study, we showed, by using various recombinant cytochrome P450 (CYP)2D enzymes and anti-CYP2D4- or P450c21-specific antibodies, that rat brain microsomal steroid 21-hydroxylation is catalyzed not by P450c21, but by CYP2D isoforms. Rat CYP2D4 and human CYP2D6, which are the predominant CYP2D isoforms in the brain, possess 21-hydroxylation activity for both progesterone and 17α-hydroxyprogesterone. In rat brain microsomes, these activities were not inhibited by anti-P450c21 antibodies, but they were effectively inhibited by the CYP2D-specific chemical inhibitor quinidine and by anti-CYP2D4 antibodies. mRNA and protein of CYP2D4 were expressed throughout the brain, especially in cerebellum, striatum, pons, and medulla oblongata, whereas the mRNA and protein levels of P450c21 were extremely low or undetectable. These results support the idea that CYP2D4, not P450c21, works as steroid 21-hydroxylase in the brain. Allopregnanolone, a representative γ-aminobutyric acid receptor modulator, was also hydroxylated at the C-21 position by recombinant CYP2D4 and CYP2D6. Rat brain microsomal allopregnanolone 21-hydroxylation was inhibited by fluoxetine with an IC50 value of 2 μm, suggesting the possibility that the brain CYP2D isoforms regulate levels of neurosteroids such as allopregnanolone, and that this regulation is modified by central nervous system-active drugs such as fluoxetine.

Liquid Chromatography Analysis of Clozapine in Rat Brain Tissue, Using its Molecularly Imprinted Polymer after Administration of Toxic Dose of Drug and Lipid Emulsion Therapy

2019 ◽  
Vol 15 (3) ◽  
pp. 251-257
Author(s):  
Bahareh Sadat Yousefsani ◽  
Seyed Ahmad Mohajeri ◽  
Mohammad Moshiri ◽  
Hossein Hosseinzadeh
Keyword(s):  
Rat Brain ◽  
Brain Tissue ◽  
Molecularly Imprinted Polymer ◽  
Lipid Emulsion ◽  
Limit Of Detection ◽  
Imprinted Polymer ◽  
Toxic Dose ◽  
Molecularly Imprinted ◽  
The Brain ◽  
Rat Brain Tissue

Background:Molecularly imprinted polymers (MIPs) are synthetic polymers that have a selective site for a given analyte, or a group of structurally related compounds, that make them ideal polymers to be used in separation processes.Objective:An optimized molecularly imprinted polymer was selected and applied for selective extraction and analysis of clozapine in rat brain tissue.Methods:A molecularly imprinted solid-phase extraction (MISPE) method was developed for preconcentration and cleanup of clozapine in rat brain samples before HPLC-UV analysis. The extraction and analytical process was calibrated in the range of 0.025-100 ppm. Clozapine recovery in this MISPE process was calculated between 99.40 and 102.96%. The limit of detection (LOD) and the limit of quantification (LOQ) of the assay were 0.003 and 0.025 ppm, respectively. Intra-day precision values for clozapine concentrations of 0.125 and 0.025 ppm were 5.30 and 3.55%, whereas inter-day precision values of these concentrations were 9.23 and 6.15%, respectively. In this study, the effect of lipid emulsion infusion in reducing the brain concentration of drug was also evaluated.Results:The data indicated that calibrated method was successfully applied for the analysis of clozapine in the real rat brain samples after administration of a toxic dose to animal. Finally, the efficacy of lipid emulsion therapy in reducing the brain tissue concentration of clozapine after toxic administration of drug was determined.Conclusion:The proposed MISPE method could be applied in the extraction and preconcentration before HPLC-UV analysis of clozapine in rat brain tissue.

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