Isoflurane anesthesia disrupts the cortical metabolome
Aaron G Baer1, Allen K Bourdon2, Joshua M Price3
1Department of Anesthesiology, University of Tennessee Medical Center, Knoxville, Tennessee.
Journal of Neurophysiology
|October 28, 2020
Summary
Investigating brain metabolome changes during anesthesia reveals key differences in the prefrontal cortex. Isoflurane anesthesia significantly alters metabolite levels, impacting neuronal networks and consciousness states.
Area of Science:
- Neuroscience
- Metabolomics
- Consciousness Studies
Background:
- Understanding brain function across different states of consciousness is crucial for neuroscience.
- The prefrontal cortex (PFC) plays a key role in modulating consciousness.
- Anesthesia is a common tool to study the loss of wakefulness.
Purpose of the Study:
- To identify similarities and differences in the brain metabolome of the prefrontal cortex during wakefulness and anesthesia.
- To explore how anesthesia-induced changes in metabolites relate to metabolic pathways and neuronal function.
Main Methods:
- Untargeted metabolomic analysis of mouse prefrontal cortex microdialysis samples.
- Comparison of metabolite profiles during wakefulness versus isoflurane anesthesia.
- Analysis using univariate and multivariate approaches, linked to Kyoto Encyclopedia of Genes and Genomes pathways.
Main Results:
- Detected 2,153 molecules, identifying 91; 61 were common to both states, 23 unique to wakefulness, and 7 unique to anesthesia.
- A fourfold significant change (q < 0.0001) was observed in 21 metabolites during anesthesia, with 11 decreasing and 10 increasing.
- Amino acids, carbohydrate metabolism molecules, and lipids decreased, while nucleosides increased during anesthesia.
Conclusions:
- Anesthesia significantly alters the prefrontal cortex metabolome, affecting molecules involved in cellular metabolism and neuronal transmission.
- These findings suggest that states of consciousness involve dynamic interactions within cortical networks, modulated by specific brain metabolites.
- Identified candidate molecules in the PFC may play a role in modulating wakefulness and its loss.
Related Concept Videos
01:20Inhalational Anesthetics: Overview
733
Inhalation anesthetics are drugs that induce general anesthesia upon inhalation. They work by increasing the sensitivity of GABAA receptors or inhibiting NMDA receptors, leading to a decrease in central nervous system activity. The depth of anesthesia can be rapidly adjusted by changing the concentration of the inhaled gas. Some common examples of inhalational anesthetics include volatile liquids like isoflurane, desflurane, sevoflurane and gases like xenon and nitrous oxide. Isoflurane, a...
733
01:24Parenteral Anesthetics: Overview
454
Intravenous anesthetics are drugs administered parenterally to induce anesthesia or sedation. Propofol is a widely used agent formulated as a 1% emulsion in soybean oil, glycerol, and egg phosphatide. It induces rapid anesthesia primarily due to its rapid distribution from the bloodstream to target tissues and is metabolized in the liver. However, it can cause significant pain on injection and hypertriglyceridemia. Fospropofol, a water-based prodrug of propofol, lacks these adverse effects.
454
01:24General Anesthesia: Overview
436
Anesthesia is a medical procedure that uses drugs for CNS suppression to enable painless surgeries and procedures. The selection of anesthetics is influenced by their pharmacokinetic properties, side effects, and patient characteristics. Various types of anesthesia include general, local, regional, spinal, and inhalational.
General anesthesia induces unconsciousness in the whole body, while the others target specific areas or sensations. It is administered to minimize adverse effects, maintain...
General anesthesia induces unconsciousness in the whole body, while the others target specific areas or sensations. It is administered to minimize adverse effects, maintain...
436
01:22Stages of General Anesthesia
1.2K
Various sedation levels offer significant advantages in facilitating procedural interventions for patients undergoing medical or invasive surgical procedures. These levels span from anxiolysis to general anesthesia, providing a spectrum of sedative effects to cater to specific patient needs. Anxiolysis reduces anxiety and is achieved through minimal sedation, enabling patients to remain awake and responsive while feeling more at ease during the procedure. This level can benefit minor...
1.2K
01:20Sedatives and Hypnotics Drugs: Barbiturates
729
Sedatives and hypnotics encompass a drug class that acts on the central nervous system (CNS) to alleviate anxiety, promote relaxation and induce sleep.These drugs function by amplifying the actions of the neurotransmitter γ-aminobutyric acid (GABA), resulting in reduced neuronal activity. Barbiturates, a subset of sedatives and hypnotics first synthesized in the late 1800s, are categorized into ultra-short, short, intermediate, and long-acting groups based on their duration of effect. A...
729
01:17Sedatives and Hypnotics Drugs: Miscellaneous Agents
360
Sedatives and hypnotics encompass a wide range of substances, each with its unique mechanism of action, uses, and potential adverse effects.
Melatonin congeners like ramelteon (Rozerem) and tasimelteon (Hetlioz) selectively bind to melatonin receptors (MT1 and MT2) and thus mimic the actions of melatonin, a hormone that regulates sleep-wake cycles. Tasimelteon is primarily used for non-24-hour sleep-wake disorder, common in blind patients. They are also used to treat conditions like insomnia...
Melatonin congeners like ramelteon (Rozerem) and tasimelteon (Hetlioz) selectively bind to melatonin receptors (MT1 and MT2) and thus mimic the actions of melatonin, a hormone that regulates sleep-wake cycles. Tasimelteon is primarily used for non-24-hour sleep-wake disorder, common in blind patients. They are also used to treat conditions like insomnia...
360