Cellular stress and AMPK links metformin and diverse compounds with accelerated emergence from anesthesia and potential recovery from disorders of consciousness.
Medical Hypotheses March 1, 2019 Jahahreeh Finley
The neural correlates of consciousness and how general anesthetics cause loss of consciousness remain poorly understood. General anesthetics like propofol and inhalational agents induce loss of consciousness partly by potentiating chloride influx through the GABAA receptor, leading to neural inhibition. These agents also cause paradoxical excitation at low doses. AMPK, a kinase activated by cellular stress such as increases in calcium and reactive oxygen species, is found throughout the mammalian brain. Neurotransmitters that promote wakefulness and arousal activate AMPK, as do several general anesthetics and compounds that accelerate emergence from anesthesia. The authors propose that cellular stress-induced AMPK activation links wakefulness, arousal, and consciousness with paradoxical excitation and accelerated emergence from anesthesia. AMPK activation may also enhance brain repair and promote recovery from disorders of consciousness.