GABA and sevoflurane

Neonatal anesthesia, while often essential for surgeries or imaging procedures, is accompanied by significant risks to redox balance in the brain due to the relatively weak antioxidant system in children. Oxidative stress is characterized by concentrations of reactive oxygen species (ROS) that are elevated beyond what can be accommodated by the antioxidant defense system. In neonatal anesthesia, this has been proposed to be a contributing factor to some of the negative consequences (e.g., learning deficits and behavioral abnormalities) that are associated with early anesthetic exposure...

Flumazenil, a gamma-aminobutyric acid receptor antagonist, can promote arousal even under general anesthesia without the use of benzodiazepines. We hypothesized that flumazenil could promote arousal and reduce emergence agitation in patients undergoing orthognathic surgery with sevoflurane anesthesia. One hundred and two patients were randomly allocated to the control or flumazenil group. Saline or flumazenil was administered at the end of the surgery. The incidence of emergence agitation was measured by using Aono's four-point scale, with scores of 3 and 4 indicating emergence agitation...

Human and animal studies have elucidated the apparent neurodevelopmental effects resulting from neonatal anesthesia. Observations of learning and behavioral deficits in children, who were exposed to anesthesia early in development, have instigated a flurry of studies that have predominantly utilized animal models to further interrogate the mechanisms of neonatal anesthesia-induced neurotoxicity. Specifically, while neonatal anesthesia has demonstrated its propensity to affect multiple cell types in the brain, it has shown to have a particularly detrimental effect on the gamma aminobutyric acid (GABA)ergic system, which contributes to the observed learning and behavioral deficits...

As a gamma-aminobutyric acid type A receptor agonist sevoflurane is a common general anesthetic used in anesthesia and affects the neural development in offspring. We hypothesized that sevoflurane could regulate interneurons via the neuregulin-1-epidermal growth factor receptor-4 (NRG1-ErbB4) pathway in the entorhinal cortex (ECT) of the middle pregnancy. Six female rats in middle pregnancy (14.5 days of pregnancy) were randomly and equally divided into sevoflurane (SeV) and control groups. The rats in the SeV group were exposed to 4% sevoflurane for 3 hours...

Understanding the different mechanisms associated with different anesthetic targeted receptors is critical towards identifying accurate long-term outcome measures as a result of early-life anesthetic exposure. We examined changes in GABAA receptor mediated neurotransmission by a predominately GABAA receptor targeted anesthetic, sevoflurane or a predominately NMDA receptor targeted anesthetic, ketamine. Postnatal day 7 male mice were exposed to sevoflurane or ketamine and examined as adults for changes in inhibitory neurotransmission and its associated change in induced seizure activity...

OBJECTIVE: The aim of this study was to determine the anesthesia-promoting effects of hydroxyzine on electroencephalograms during sevoflurane anesthesia and during propofol anesthesia. METHODS: We analyzed 40 patients scheduled for elective surgery under sevoflurane anesthesia (n = 20) or propofol anesthesia (n = 20). Anesthesia was adjusted at a bispectral index value of 50-60, and then 0.5 mg/kg of hydroxyzine was administered intravenously. We analyzed frontal electroencephalograms before and after hydroxyzine injection with power spectral and bicoherence analyses, which are suitable for assessing the anesthetic depth induced by γ-aminobutyric acid (GABA)ergic anesthetics...

Most surgical procedures require general anesthesia, which is a reversible deep sedation state lacking all perception. The induction of this state is possible because of complex molecular and neuronal network actions of general anesthetics (GAs) and other pharmacological agents. Laboratory and clinical studies indicate that the effects of GAs may not be completely reversible upon anesthesia withdrawal. The long-term neurocognitive effects of GAs, especially when administered at the extremes of ages, are an increasingly recognized health concern and the subject of extensive laboratory and clinical research...

Many general anesthetics potentiate gamma-aminobutyric acid (GABA) A receptors but their neuroanatomic sites of action are less clear. GABAergic neurons in the rostromedial tegmental nucleus (RMTg) send inhibitory projections to multiple arousal-promoting nuclei, but the role of these neurons in modulating consciousness is unknown. In this study, designer receptors exclusively activated by designer drugs (DREADDs) were targeted to RMTg GABAergic neurons of Vgat-ires-Cre mice. DREADDs expression was found in the RMTg and other brainstem regions...

Testosterone (T), predominantly acting through its derivative 17β-estradiol (E2), regulates the brain's sexual differentiation in rodents during the perinatal sensitive period, which mirrors the window of vulnerability to the adverse effects of general anesthetics. The mechanisms of anesthesia's adverse effects are poorly understood. We investigated whether sevoflurane alters T and E2 levels and whether they contribute to sevoflurane's acute adverse effects in postnatal day 5 Sprague-Dawley rats. The rats underwent electroencephalography recordings for 2 h of baseline activity or for 1 h before and another hour during 2...

Background: In rodents, the period of increased vulnerability to the developmental effects of general anesthetics coincides with the period of age-specific organizing (masculinizing) effects of the major female sex hormone 17β-estradiol (E2) in the male brain and excitatory GABA type A receptor (GABA A R) signaling. We studied whether E2 synthesis and excitatory GABA A R signaling are involved in the mediation of the developmental effects of sevoflurane in male rats. Methods: Male Sprague-Dawley rats were pretreated with the inhibitors of E2 synthesis, formestane, or the Na+ -K+ -2Cl- (NKCC1) Cl- importer, bumetanide, prior to sevoflurane exposure for 6 h on postnatal (P) day 4, P5, or P6...

The balance of excitatory and inhibitory neurons in the central nervous system is critical for maintaining brain function and sevoflurane, a general anesthetic and an GABA receptor modulator, may change the balance of excitatory and inhibitory neurons in the cortex during early brain development. Herein, we investigated whether prenatal sevoflurane exposure (PSE) disturbs cortical neuronal development and brain function. Pregnant rats at the gestational day 14.5 were subjected to sevoflurane exposure at 3.0% for 3 h and their offspring were studied thereafter...

Despite persistent clinical use for over 170 years, the neuronal mechanisms by which general anesthetics produce hypnosis remain unclear. Previous studies suggest that anesthetics exert hypnotic effects by acting on endogenous arousal circuits. Recently, it has been shown that the medial parabrachial nucleus (MPB) is a novel wake-promoting component in the dorsolateral pons. However, it is not known whether and how the MPB contributes to anesthetic-induced hypnosis. Here, we investigated the action of sevoflurane, a widely used volatile anesthetic agent that best represents the drug class of halogenated ethers, on MPB neurons in mice...

BACKGROUND: Deficiencies in neurocognitive function have been found in late childhood or adolescence in patients who had prolonged and/or repeated early-life general anesthesia. Animal studies suggest that anesthetic-induced impairment in the neuron-specific K+ -2Cl- (Kcc2) Cl- exporter expression, which regulates developmental maturation of GABA type A receptor (GABAA R) signaling from excitatory to inhibitory, may play a mediating role. We tested whether the DNA methyltransferase (DNMT) inhibitor decitabine ameliorates the anesthetic's adverse effects...

BACKGROUND: Volatile anaesthetics (VAs) are the most widely used compounds to induce reversible loss of consciousness and maintain general anaesthesia during surgical interventions. Although the mechanism of their action is not yet fully understood, it is generally believed, that VAs depress central nervous system functions mainly through modulation of ion channels in the neuronal membrane, including 2-pore-domain K+ channels, GABA and NMDA receptors. Recent research also reported their action on nociceptive and thermosensitive TRP channels expressed in the peripheral nervous system, including TRPV1, TRPA1, and TRPM8...

Background Patients with acute aneurysmal subarachnoid hemorrhage (aSAH) experience excruciating headache that is difficult to manage in resource-constrained settings. Pregabalin's (β-isobutyl-GABA) analgesic, antiepileptic, and antiemetic properties make it an attractive adjuvant in pain management for these patients. Methods We conducted a double-blind, placebo-controlled, randomized clinical trial on 40 aSAH patients undergoing aneurysmal clipping to assess the effect of perioperative pregabalin in decreasing perioperative headache, anesthetic, and opioid requirement...

The cation-chloride cotransporters Na+ -K+ -2Cl- -1 (NKCC1) and K+ -2Cl- -2 (KCC2) critically regulate neuronal responses to gamma-aminobutyric acid (GABA). NKCC1 renders GABA excitatory in immature neurons while expression of KCC2 signals GABA maturation to its inhibitory role. Imbalances in NKCC1/KCC2 alter GABA neurotransmission, which may contribute to hyperexcitability and blunted inhibition in neurocircuitry after neonatal exposure to anesthesia. Thus, we hypothesized that anesthetics may dysregulate NKCC1 and/or KCC2 in developing brain...

Exposure to commonly used anesthetics is associated with widespread neuroapoptosis in neonatal animals. Vulnerability of developing hippocampal dentate gyrus granule cells to anesthetic neurotoxicity peaks approximately 2 weeks after cell birth, as measured by bromodeoxyuridine birth dating, regardless of the age of the animal. The present study examined whether the vulnerable window can be further characterized by utilizing a transgenic approach. Proopiomelanocortin enhanced green fluorescent protein (POMC-EGFP) mice (postnatal day 21) were exposed to 3% sevoflurane for 6 h...

Volatile general anesthetics are used commonly in adults and children, yet their mechanisms of action are complex and the changes in single unit firing and synaptic activity that underlie the broad decreases in neuronal activity induced by these drugs have not been well characterized. Capturing such changes throughout the anesthesia process is important for comparing the effects of different anesthetics and gaining a better understanding of their mechanisms of action and their impact on different brain regions...

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...

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...