Effect of centrally administered gamma-aminobutyric acid on metabolic function

1986 ◽  
Vol 61 (2) ◽  
pp. 472-476 ◽  
Author(s):  
M. P. Kneussl ◽  
P. Pappagianopoulos ◽  
B. Hoop ◽  
H. Kazemi

gamma-Aminobutyric acid (GABA) content of the brain increases during hypoxia and hypercapnia and GABA by itself is a central ventilatory depressant and may depress metabolism as well. Therefore the effect of centrally administered GABA by ventriculocisternal perfusion on O2 consumption (VO2) and CO2 production (VCO2) was studied in pentobarbital-anesthetized dogs. GABA (30 mM) in mock cerebrospinal fluid (CSF) was perfused for 15 min at the rate of 1.0 ml/min followed by perfusion with mock CSF alone. Body temperature, perfusion pressure, and CSF pH were kept constant. Minute ventilation (VE) was kept constant mechanically. Under these conditions, VO2, VCO2, alveolar ventilation (VA), and relative pulmonary dead space volume (VD/VT) were measured. During perfusion with 30 mM GABA, mean VO2 (+/- SE) decreased from 96.5 +/- 3.3 to 81.9 +/- 5.1 ml/min, VCO2 from 72.1 +/- 3.8 to 60.7 +/- 3.0 ml/min, and VA from 1.7 +/- 0.1 to 1.3 +/- 0.1 l/min. VD/VT increased from 0.55 +/- 0.02 to 0.65 +/- 0.01. Perfusion with mock CSF alone restored these parameters to initial levels within 15 min. We conclude that centrally administered GABA depresses VO2 and VCO2. This reduction in metabolic function is independent of the central modulatory effects of GABA on respiration.

Author(s):  
T.R. Winder ◽  
G.Y. Minuk ◽  
E.J. Sargeant ◽  
T.P. Seland

ABSTRACT:In order to determine whether disturbances in GABA homeostasis might play a role in the pathogenesis of sepsis-related encephalopathy, serum and brain tissue GABA concentrations from six areas of the brain (cortex, diencephalon, striatum, hippocampus, midbrain, and pons-medulla) were determined in a rat model of bacterial sepsis (cecal ligation and perforation). The results were compared to those obtained from sham operated control animals. All septic animals demonstrated clinical signs of encephalopathy and had elevated serum GABA levels (0.92 ± 0.3 uM versus 0.48 ± 0.15 in controls, p < 0.01). GABA content in the specific subcompartments of the brain, however, were similar in the two groups. These results indicate that although serum GABA levels are elevated during sepsis, GABA is unlikely to play an important role in the pathogenesis of sepsis-related encephalopathy.


2021 ◽  
Author(s):  
Quangang Yang

Background: In mechanical ventilation, there are still some challenges to turn a modern ventilator into a fully reactive device, such as lack of a comprehensive target variable and the unbridged gap between input parameters and output results. This paper aims to present a state ventilation which can provide a measure of two primary, but heterogenous, ventilation support goals. The paper also tries to develop a method to compute, rather than estimate, respiratory parameters to obtain the underlying causal information. Methods: This paper presents a state ventilation, which is calculated based on minute ventilation and blood gas partial pressures, to evaluate the efficacy of ventilation support and indicate disease progression. Through mathematical analysis, formulae are derived to compute dead space volume/ventilation, alveolar ventilation, and CO2 production. Results: Measurements from a reported clinical study are used to verify the analysis and demonstrate the application of derived formulae. The state ventilation gives the expected trend to show patient status, and the calculated mean values of dead space volume, alveolar ventilation, and CO2 production are 158mL, 8.8L/m, and 0.45L/m respectively for a group of patients. Discussions and Conclusions: State ventilation can be used as a target variable since it reflects patient respiratory effort and gas exchange. The derived formulas provide a means to accurately and continuously compute respiratory parameters using routinely available measurements to characterize the impact of different contributing factors.


1984 ◽  
Vol 56 (4) ◽  
pp. 849-856 ◽  
Author(s):  
J. Hedner ◽  
T. Hedner ◽  
P. Wessberg ◽  
J. Jonason

Intracerebroventricular administration of gamma-aminobutyric acid (GABA) or intraperitoneal injection of the GABA transaminase A inhibitor aminooxyacetic acid (AOAA) depressed ventilation in halothane-anesthetized rats. The depression was due to changes in both respiratory frequency (f) and tidal volume (VT) after GABA, whereas AOAA decreased only f. Intracerebroventricular GABA decreased inspiratory drive (VT/TI; intrapulmonary pressure at 100 ms) but did not change the bulbopontine setting of inspiratory duration (TI). Moreover, respiratory duty cycle (TI/TT) was decreased, and the ventilatory response to CO2 exposure was blunted. The ventilatory depression induced by GABA was reversed by the GABA antagonist bicuculline. The GABA content measured 45 min after AOAA administration was significantly increased in the whole brain, the hemispheres, striatum, and lower spinal cord regions. Whole-brain GABA content was significantly correlated to the changes in f, minute ventilation, TI, expiratory duration (TE), and total cycle duration. Furthermore, there was a significant negative correlation between brain stem GABA content and TI/TT but not VT/TI. In summary, GABA seems to interact with the central regulation of respiration at different levels in the brain. The main effect of increased endogenous concentrations of GABA is, however, a decrease in respiratory frequency due to a prolongation in TE.


2018 ◽  
Vol 14 (5) ◽  
pp. 16-24 ◽  
Author(s):  
P. Török ◽  
F. Depta ◽  
V. Donic ◽  
M. Nosál’ ◽  
S. Imrecze ◽  
...  

The purpose of the study was to compare the relationship between the dead space volume and tidal volume (VD/VT) using volumetric capnography (VCap) during pressure controlled (PCV) and pressure supported (PSV) ventilation mode in the postoperative period.Materials and methods. 30 randomly assigned cardiac surgical patients undergoing CABG (coronary artery bypass grafting) using ECC (extracorporeal circuit) were included in an observational, prospective study. Patients were connected to the ventilator immediately after ICU admission. After that, monitoring VD/VT, CO2 production (VECO2) as well as ventilation parameters was carried out. The parameters during PCV and PSV mode were statistically evaluated using t-test.Results. Expiratory CO2 (ETCO2) concentration were not significantly different in both PCV or PSV (p=NS), although both VECO2 and minute ventilation (MV) increased during PSV mode (p<0.01). VD/VT in PSV mode was lower than in PCV. Gas exchange represented by alveolar ventilation (VA) was better during PSV (p<0.01). VA was also higher during PSV (p<0.05). The calculated VD/VT ratio differed between PCV and PSV mode (p<0.01).Conclusion. VCap represents a tool for monitoring of CO2 exchange effectivness. We registered a decrease in VD/VT with improved alveolar ventilation (VA) in PSV mode. VCap seems to be a suitable instrument for adjustment of protective lung ventilation.


2015 ◽  
Vol 96 (5) ◽  
pp. 806-810
Author(s):  
R V Deev ◽  
Yu M Shatrova ◽  
A I Sinitskiy ◽  
N S Molchanova ◽  
A K Yunusova ◽  
...  

Aim. To study the changes in levels of biogenic amines-neurotransmitters in the brain at experimental post-traumatic stress disorder development in rats. Methods. Post-traumatic stress disorder was modeled by keeping 48 outbred male rats in under constant and inescapable strong unconditioned stimulus. The control group included 16 intact animals, not exposed to stress influences. The levels of 3,4-dihydroxyphenylalanine, dopamine, norepinephrine, epinephrine and gamma-aminobutyric acid were determined by fluorometric methods. Behavioral activity of animals was evaluated on the day 3, 7, 10 and 14 by «open field» and «elevated plus maze» actinographs. Results. When comparing the concentrations of studied neurotransmitters in the brain of control animals with experimental groups, reflecting the development of post-traumatic stress disorder at the time, adrenaline and 3,4-dihydroxyphenylalanine levels were increased on the third day, level of norepinephrine was reduced on the seventh day, 3,4-dihydroxyphenylalanine, dopamine, norepinephrine levels were elevaled, gamma-aminobutyric acid level was reduced on the tenth day, gamma-aminobutyric acid level was increased on the fourteenth day after the stress. Conclusion. According to the results of the correlation analysis, the largest contribution to the development of behavioral disorders are made by altered brain level of gamma-aminobutyric acid at the time of post-traumatic stress disorder formation (tenth and fourteenth day). At the earlier stages (third and seventh day), the relationship of rats behavioral activity and altered 3,4-dihydroxyphenylalanine and norepinephrine brain levels was shown.


2018 ◽  
Vol 51 (5) ◽  
pp. 1702251 ◽  
Author(s):  
Paolo Biselli ◽  
Kathrin Fricke ◽  
Ludger Grote ◽  
Andrew T. Braun ◽  
Jason Kirkness ◽  
...  

Nasal high flow (NHF) reduces minute ventilation and ventilatory loads during sleep but the mechanisms are not clear. We hypothesised NHF reduces ventilation in proportion to physiological but not anatomical dead space.11 subjects (five controls and six chronic obstructive pulmonary disease (COPD) patients) underwent polysomnography with transcutaneous carbon dioxide (CO2) monitoring under a metabolic hood. During stable non-rapid eye movement stage 2 sleep, subjects received NHF (20 L·min−1) intermittently for periods of 5–10 min. We measured CO2 production and calculated dead space ventilation.Controls and COPD patients responded similarly to NHF. NHF reduced minute ventilation (from 5.6±0.4 to 4.8±0.4 L·min−1; p<0.05) and tidal volume (from 0.34±0.03 to 0.3±0.03 L; p<0.05) without a change in energy expenditure, transcutaneous CO2 or alveolar ventilation. There was a significant decrease in dead space ventilation (from 2.5±0.4 to 1.6±0.4 L·min−1; p<0.05), but not in respiratory rate. The reduction in dead space ventilation correlated with baseline physiological dead space fraction (r2=0.36; p<0.05), but not with respiratory rate or anatomical dead space volume.During sleep, NHF decreases minute ventilation due to an overall reduction in dead space ventilation in proportion to the extent of baseline physiological dead space fraction.


Author(s):  
Hanagasaki Takashi ◽  

Luffa (Luffa cylindrica Roem.) is a popular vegetable in Okinawa, and it has abundant nutrients, including &gamma;-aminobutyric acid (GABA). We focused on GABA content in luffa, taking into consideration registering it as foods with functional claims in Japan. Besides, when selling cut luffa and frozen cut luffa at supermarkets, they are supposed to get browned due to air exposure and other causes. In the present study, we developed the prevention method of browning cut luffa and frozen cut luffa using 0.5 %, 1.0 %, 2.0 %, and 4.0 % ascorbic acid solution. It was found that 55 L of 4.0 % ascorbic acid solution could be used for soaking of 70 kg cut luffa to prevent browning, but GABA content decreased in food processing of luffa in the factory. Besides, GABA content in luffa fruits was found not to change during storage for 07 days at room temperature after harvest.


2009 ◽  
Vol 12 (1) ◽  
pp. 12-20 ◽  
Author(s):  
Evgeniya A. Zyablitseva ◽  
Nikolay S. Kositsyn ◽  
Galina I. Shul'gina

The research described here investigates the role played by inhibitory processes in the discriminations made by the nervous system of humans and animals between familiar and unfamiliar and significant and nonsignificant events. This research compared the effects of two inhibitory mediators of gamma-aminobutyric acid (GABA): 1) phenibut, a nonselective agonist of ionotropic GABAAand metabotropic GABABreceptors and 2) gaboxadol a selective agonist of ionotropic GABAAreceptors on the process of developing active defensive and inhibitory conditioned reflexes in alert non-immobilized rabbits. It was found that phenibut, but not gaboxadol, accelerates the development of defensive reflexes at an early stage of conditioning. Both phenibut and gaboxadol facilitate the development of conditioned inhibition, but the effect of gaboxadol occurs at later stages of conditioning and is less stable than that of phenibut. The earlier and more stable effects of phenibut, as compared to gaboxadol, on storage in memory of the inhibitory significance of a stimulus may occur because GABABreceptors play the dominant role in the development of internal inhibition during an early stage of conditioning. On the other hand this may occur because the participation of both GABAAand GABABreceptors are essential to the process. We discuss the polyfunctionality of GABA receptors as a function of their structure and the positions of the relevant neurons in the brain as this factor can affect regulation of various types of psychological processes.


Author(s):  
Juncai Pu ◽  
Yiyun Liu ◽  
Siwen Gui ◽  
Lu Tian ◽  
Yue Yu ◽  
...  

AbstractExtensive research has been carried out on the metabolomic changes in animal models of depression; however, there is no general agreement about which metabolites exhibit constant changes. Therefore, the aim of this study was to identify consistently altered metabolites in large-scale metabolomics studies of depression models. We performed vote counting analyses to identify consistently upregulated or downregulated metabolites in the brain, blood, and urine of animal models of depression based on 3743 differential metabolites from 241 animal metabolomics studies. We found that serotonin, dopamine, gamma-aminobutyric acid, norepinephrine, N-acetyl-L-aspartic acid, anandamide, and tryptophan were downregulated in the brain, while kynurenine, myo-inositol, hydroxykynurenine, and the kynurenine to tryptophan ratio were upregulated. Regarding blood metabolites, tryptophan, leucine, tyrosine, valine, trimethylamine N-oxide, proline, oleamide, pyruvic acid, and serotonin were downregulated, while N-acetyl glycoprotein, corticosterone, and glutamine were upregulated. Moreover, citric acid, oxoglutaric acid, proline, tryptophan, creatine, betaine, L-dopa, palmitic acid, and pimelic acid were downregulated, and hippuric acid was upregulated in urine. We also identified consistently altered metabolites in the hippocampus, prefrontal cortex, serum, and plasma. These findings suggested that metabolomic changes in depression models are characterized by decreased neurotransmitter and increased kynurenine metabolite levels in the brain, decreased amino acid and increased corticosterone levels in blood, and imbalanced energy metabolism and microbial metabolites in urine. This study contributes to existing knowledge of metabolomic changes in depression and revealed that the reproducibility of candidate metabolites was inadequate in previous studies.


1988 ◽  
Vol 251 (2) ◽  
pp. 559-562 ◽  
Author(s):  
P C Caron ◽  
L J Cote ◽  
L T Kremzner

Putrescine is the major source of gamma-aminobutyric acid (GABA) in the rat adrenal gland. Diamine oxidase, and not monoamine oxidase, is essential for GABA formation from putrescine in the adrenal gland. Aminoguanidine, a diamine oxidase inhibitor, decreases the GABA concentration in the adrenal gland by more than 70% after 4 h, and almost to zero in 24 h. Studies using [14C]putrescine confirm that [14C]GABA is the major metabolite of putrescine in the adrenal gland. Inhibition of GABA transaminase by amino-oxyacetic acid does not change the GABA concentration in the adrenal gland, as compared with the brain, where the GABA concentration rises. With aminoguanidine, the turnover time of GABA originating from putrescine in the adrenal gland is 5.6 h, reflecting a slower rate of GABA metabolism compared with the brain. Since GABA in the adrenal gland is almost exclusively derived from putrescine, the role of GABA may relate to the role of putrescine as a growth factor and regulator of cell metabolism.


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