Cellular stress and AMPK links metformin and diverse compounds with accelerated emergence from anesthesia and potential recovery from disorders of consciousness.

摘要: The neural correlates of consciousness and the mechanisms by which general anesthesia (GA) modulate such to induce loss (LOC) has been described as one biggest mysteries modern medicine. Several cellular targets circuits have identified that play a critical role in LOC induced GA, including GABAA receptor ascending arousal nuclei located basal forebrain, hypothalamus, brain stem. General anesthetics (GAs) propofol inhalational agents part potentiating chloride influx through receptor, leading inhibition LOC. Interestingly, nearly all GAs used clinically may also paradoxical excitation, phenomenon promote neuronal excitation at low doses before inducing unconsciousness. Additionally, emergence from passive process occurs after anesthetic removal, is associated with lower concentrations compared induction GA. AMPK, an evolutionarily conserved kinase activated stress (e.g. increases calcium [Ca2+] and/or reactive oxygen species [ROS], etc.) lifespan healthspan several model organisms. AMPK throughout mammalian brain, neurons thalamus, striatum well pyramidal hippocampus cortex. Increases ROS Ca2+ roles glutamate, primary excitatory neurotransmitter human activates cortical neurons. Nearly every released wakefulness, arousal, acetylcholine, histamine, orexin-A, dopamine, norepinephrine. are commonly patients activate propofol, sevoflurane, isoflurane, dexmedetomidine, ketamine, midazolam). Various compounds accelerate anesthesia, thus mitigating problematic effects delayed delirium, nicotine, caffeine, forskolin, carbachol). neurotransmitters act preconditioning inhibitor bicuculline, reverses We propose novel hypothesis stress-induced activation links accelerated anesthesia. Because activators metformin nicotine proliferation differentiation stem cells subventricular zone dentate gyrus, enhance repair potential recovery disorders (i.e. minimally conscious state, vegetative coma).