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GABA and sevoflurane

Kellie A Woll, Xiaojuan Zhou, Natarajan V Bhanu, Benjamin A Garcia, Manuel Covarrubias, Keith W Miller, Roderic G Eckenhoff
Most general anesthetics enhance GABA type A (GABAA ) receptor activity at clinically relevant concentrations. Sites of action of volatile anesthetics on the GABAA receptor remain unknown, whereas sites of action of many intravenous anesthetics have been identified in GABAA receptors by using photolabeling. Here, we used photoactivatable analogs of isoflurane (AziISO) and sevoflurane (AziSEVO) to locate their sites on α1 β3 γ2L and α1 β3 GABAA receptors. As with isoflurane and sevoflurane, AziISO and AziSEVO enhanced the currents elicited by GABA...
March 5, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Janette Brohan, Basavana G Goudra
GABA (γ-aminobutyric acid) receptors, of which there are two types, are involved in inhibitory synapses within the central nervous system. The GABAA receptor (GABAAR) has a central role in modern anesthesia and sedation practice, which is evident from the high proportion of agents that target the GABAAR. Many GABAAR agonists are used in anesthesia practice and sedation, including propofol, etomidate, methohexital, thiopental, isoflurane, sevoflurane, and desflurane. There are advantages and disadvantages to each GABAAR agonist currently in clinical use...
October 2017: CNS Drugs
Veysel Erden, Cihan Güler, Seda Seven, Sevda Bağ, Ali G Kara, Şenay Kirgezen
BACKGROUND: GABA (γ-aminobutyric acid) is the primary inhibitory neurotransmitter in the CNS and well-known target for general anesthetics. In addition, the dysregulation of GABA could be involved in the etiology of major depressive disorder (MDD). In this study, we aimed to determine whether MDD has any effect on anesthetic requirement measured by Bispectral Index (BIS). METHODS: This study was designed as a prospective, observational study, registered ANZCTR (ACTRN 12616001295437), with institutional review board approval and written informed consent...
January 2018: Minerva Anestesiologica
Olutoyin A Olutoye, Byron Wycke Baker, Michael A Belfort, Oluyinka O Olutoye
There has been growing concern about the detrimental effects of certain anesthetic agents on the developing brain. Preclinical studies in small animal models as well as nonhuman primates suggested loss or death of brain cells and consequent impaired neurocognitive function following anesthetic exposure in neonates and late gestation fetuses. Human studies in this area are limited and currently inconclusive. On Dec. 14, 2016, the US Food and Drug Administration issued a warning regarding impaired brain development in children following exposure to certain anesthetic agents used for general anesthesia, namely the inhalational anesthetics isoflurane, sevoflurane, and desflurane, and the intravenous agents propofol and midazolam, in the third trimester of pregnancy...
January 2018: American Journal of Obstetrics and Gynecology
Thomas Seidemann, Claudia Spies, Rudolf Morgenstern, Klaus-Dieter Wernecke, Nicolai Netzhammer
BACKGROUND: Alcohol withdrawal syndrome is a potentially life-threatening condition, which can occur when patients with alcohol use disorders undergo general anesthesia. Excitatory amino acids, such as glutamate, act as neurotransmitters and are known to play a key role in alcohol withdrawal syndrome. To understand this process better, we investigated the influence of isoflurane, sevoflurane, and desflurane anesthesia on the profile of excitatory and inhibitory amino acids in the nucleus accumbens (NAcc) of alcohol-withdrawn rats (AWR)...
2017: PloS One
Maiko Satomoto, Zhongliang Sun, Yushi U Adachi, Koshi Makita
BACKGROUND: Neonatal mice exposed to sevoflurane show certain cognitive and behavioral impairments in adulthood. However, the mechanisms underlying long-term cognitive deficits induced by sevoflurane exposure remain unknown. The present study was performed to investigate whether there is differential neuronal activation between naive mice and sevoflurane-exposed neonates in fear-conditioning tests based on immediate early gene (c-Fos) expression. METHODS: Male mice were exposed to 3% sevoflurane (SEVO group) or carrier gas alone (no anesthesia, NA group) for 6 hours on postnatal day 6...
January 2018: Journal of Neurosurgical Anesthesiology
Guanghai Liu, Tiangui Zhu, Aihua Zhang, Feng Li, Weidong Qian, Bin Qian
OBJECTIVE: Children with repeated exposures to anesthesia at an early age are at an increased risk of cognitive impairment. Data in the literature link increased developmental depolarizing γ-aminobutyric acid (GABA) type A receptor (GABAAR) at younger age to neurodevelopmental disorders. Here we investigated the involvement of GABAergic signaling during development in mediating the adverse effects of repeated sevoflurane exposures. METHODS: Sprague-Dawley male rats received repeated exposures to 3 % sevoflurane for 2 h daily for 3 consecutive days on postnatal days (P) 4, 5, and 6; maternally separated and unseparated rats served as controls...
October 2016: Journal of Anesthesia
Jiaqiang Zhang, Changqing Xu, Dyanet L Puentes, Christoph N Seubert, Nikolaus Gravenstein, Anatoly E Martynyuk
UNLABELLED: Recent studies have demonstrated that long-term developmental effects of neonatal anesthesia were more prominent in males. We tested whether steroids, in general, and sex steroids, in particular, are involved in the mediation of sevoflurane-caused paradoxical cortical seizures during the early postnatal period. METHODS: Cortical electroencephalograms, hippocampal synaptic activity, serum levels of steroids and the loss of the righting reflex (LORR), a marker of anesthetic effect, were measured on postnatal days 4-6 in Sprague Dawley rats of both genders exposed to 2...
2016: Neuroendocrinology
Changqing Xu, Sijie Tan, Jiaqiang Zhang, Christoph N Seubert, Nikolaus Gravenstein, Colin Sumners, Terrie Vasilopoulos, Anatoly E Martynyuk
BACKGROUND: 1.5 million children under 12 months of age are exposed to general anesthesia annually in the United States alone. Human and especially animal studies provide evidence that exposure to general anesthesia during the early postnatal period may lead to long-term neurocognitive abnormalities via poorly understood mechanisms. We investigated whether an immature stress response system and γ-aminobutyric acid (GABA) type A receptor activities are involved in mediating these abnormalities...
October 2015: Psychoneuroendocrinology
Kodai Ikemoto, Tadahiko Ishiyama, Noriyuki Shintani, Nobumasa Asano, Daniel I Sessler, Takashi Matsukawa
BACKGROUND: JM-1232(-) is a novel anesthetic agent which acts through gamma-aminobutyric acid receptors. Cerebral pial vascular effects of JM-1232(-) are unknown. We thus evaluated topical and intravenous effects of JM-1232(-) on cerebral pial microvessels in rabbits, and the extent to which carbon dioxide (CO2) reactivity is preserved. METHODS: Closed cranial windows were used to visualize cerebral pial circulation in 29 Japanese white rabbits. In the first experiment, the cranial window was superfused with increasing concentrations of JM-1232(-): 10(-11), 10(-9), 10(-7), 10(-5) mol/L, n = 8 per concentration...
2015: BMC Anesthesiology
Jianlei Qiu, Pengcai Shi, Wude Mao, Yuyi Zhao, Wenshuai Liu, Yuelan Wang
BACKGROUND: At present, sevoflurane inhalation anesthesia used on infants is well-known. But long-time exposure to inhalation anesthetic could cause neurologic disorder, especially nerve degeneration in infant and developing brain. The central nervous system degeneration of infants could affect the memory and cognitive function. γ-Aminobutyric acid (GABA) is a known inhibitory neurotransmitter in central nervous system. Inhalation anesthetic sevoflurane may activate GABAA receptor to inhibit central nervous system, leading to apoptosis of neural degeneration, cognitive dysfunction in the critical period of brain development...
2015: BMC Anesthesiology
Nozomi Ando, Yusuke Sugasawa, Ritsuko Inoue, Toshihiko Aosaki, Masami Miura, Kinya Nishimura
The volatile anesthetic sevoflurane, which is widely used in pediatric surgery, has proposed effects on GABAA receptor-mediated extrasynaptic tonic inhibition. In the developing striatum, medium-sized spiny projection neurons have tonic GABA currents, which function in the excitatory/inhibitory balance and maturation of striatal neural circuits. In this study, we examined the effects of sevoflurane on the tonic GABA currents of medium spiny neurons in developing striatal slices. Sevoflurane strongly increased GABAA receptor-mediated tonic conductance at postnatal days 3-35...
October 2014: European Journal of Neuroscience
Peng Liang, Cheng Zhou, Kai-Yu Li, Li-Juan Guo, Bin Liu, Jin Liu
OBJECTIVE: It is controversial that whether the GABA receptors contribute to the hypnotic action of volatile anesthetics. This study was to detect the effect of GABA receptors on the hypnotic action of volatile anesthetics by evaluation of the effect of intravenous flumazenil on sevoflurane minimum alveolar anesthetic concentration-awake (MAC-Awake) and emergence mental status. METHODS: This study included two steps. Firstly, 49 healthy patients, aged 20-40 years scheduled for elective surgeries, were randomly assigned to two groups, a flumazenil group (n=24) and a saline group (n=25)...
2014: International Journal of Clinical and Experimental Medicine
Byung-Gun Lim, Feng-Yan Shen, Young-Beom Kim, Woong Bin Kim, Yoon Sik Kim, Hee Chul Han, Mi-Kyoung Lee, Myoung-Hoon Kong, Yang In Kim
Hyperexcitatory behaviors occurring after sevoflurane anesthesia are of serious clinical concern, but the underlying mechanism is unknown. These behaviors may result from the potentiation by sevoflurane of GABAergic depolarization/excitation in neocortical neurons, cells implicated in the genesis of consciousness and arousal. The current study sought to provide evidence for this hypothesis with rats, the neocortical neurons of which are known to respond to GABA (γ-aminobutyric acid) with depolarization/excitation at early stages of development (i...
2014: ASN Neuro
Paulo H C Diniz, Cristina Guatimosim, Nancy S Binda, Flávia L P Costa, Marcus V Gomez, Renato S Gomez
GABA is an inhibitory neurotransmitter that appears to be associated with the action of volatile anesthetics. These anesthetics potentiate GABA-induced postsynaptic currents by synaptic GABAA receptors, although recent evidence suggests that these agents also significantly affect extrasynaptic GABA receptors. However, the effect of volatile anesthetics on the extracellular concentration of GABA in the central nervous system has not been fully established. In the present study, rat brain cortical slices loaded with [(3)H]GABA were used to investigate the effect of halothane and sevoflurane on the extracellular accumulation of this neurotransmitter...
January 2014: Cellular and Molecular Neurobiology
C Van den Boomen, J C de Graaff, T P V M de Jong, C J Kalkman, C Kemner
Gamma-Aminobutyric Acid (GABA) inhibitory interneurons play an important role in visual processing, as is revealed by studies administering drugs in human and monkey adults. Investigating this process in children requires different methodologies, due to ethical considerations. The current study aimed to investigate whether a new method, being general anesthesia using Sevoflurane, can be used to trace the effects of GABAergic modulation on visual brain functioning in children. To this aim, visual processing was investigated in children aged 4-12 years who were scheduled for minor urologic procedures under general anesthesia in day-care treatment...
2013: Frontiers in Cellular Neuroscience
Veit-Simon Eckle, Sabrina Hauser, Berthold Drexler, Bernd Antkowiak, Christian Grasshoff
BACKGROUND: The ventral horn is a major substrate in mediating the immobilizing properties of the volatile anesthetic sevoflurane in the spinal cord. In this neuronal network, action potential firing is controlled by GABA(A) and glycine receptors. Both types of ion channels are sensitive to volatile anesthetics, but their role in mediating anesthetic-induced inhibition of spinal locomotor networks is not fully understood. METHODOLOGY/PRINCIPAL FINDINGS: To compare the effects of sevoflurane on GABAergic and glycinergic inhibitory postsynaptic currents (IPSCs) whole-cell voltage-clamp recordings from ventral horn interneurons were carried out in organotypic spinal cultures...
2013: PloS One
I Lecker, Y Yin, D S Wang, B A Orser
BACKGROUND: Animal studies have shown that memory deficits in the early post-anaesthetic period can be prevented by pre-treatment with an inverse agonist that preferentially inhibits α5 subunit-containing γ-aminobutyric acid type A (α5GABA(A)) receptors. The goal of this in vitro study was to determine whether inverse agonists that inhibit α5GABA(A) receptors reduce anaesthetic potentiation of GABAA receptor activity. METHODS: Cultures of hippocampal neurones were prepared from Swiss white mice, wild-type mice (genetic background C57BL/6J and Sv129Ev) and α5GABA(A)receptor null mutant (Gabra5-/-) mice...
June 2013: British Journal of Anaesthesia
Susann Boretius, Roland Tammer, Thomas Michaelis, Jürgen Brockmöller, Jens Frahm
Halogenated volatile anesthetics (HVA) are widely used in medicine and research but their effects on brain metabolism in intact organisms are still largely unknown. Here, localized proton magnetic resonance spectroscopy (MRS) of anesthetized mice was applied to evaluate HVA effects on cerebral metabolites in vivo. Experimental protocols combined different concentrations of isoflurane, halothane, sevoflurane, and desflurane with known modulators of adrenergic, GABAergic, and glutamatergic neurotransmission. As a most striking finding, brain lactate increased in individual mice from 1...
April 1, 2013: NeuroImage
Mark Coburn, Robert D Sanders, Mervyn Maze, Rolf Rossaint
BACKGROUND: Strategies to protect the brain from postoperative delirium (POD) after hip fracture are urgently needed. The development of delirium often is associated with the loss of independence, poor functional recovery, and increased morbidity, as well as increases in length of hospital stay, discharges to nursing facilities, and healthcare costs. We hypothesize that xenon may reduce the burden of POD, (i) by avoiding the need to provide anesthesia with a drug that targets the γ-amino-butyric acid (GABA)A receptor and (ii) through beneficial anesthetic and organ-protective effects...
September 27, 2012: Trials
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