Time: Thursday, October 11, 2018 at 11:00 AM.
Venue: IRC 5 lecture hall.
Title: Anesthetic Mechanisms: From molecules to humans
Dr. Zheng , M.D., Ph.D.
Department of Anesthesia and Critical Care
University of Chicago.
Tens of millions of patients worldwide, from newborn to elderly, receive anesthesia each year. The mechanisms of Anesthetics remain largely unresolved despite significant progress over the past several decades. Recently, evidence has been uncovered suggesting that anesthetics are neurotoxic to the developing brain in animals and possibly in humans. In 2016, the FDA issued a warning about the potential long-term risks to cognitive functions in children who receive multiple or prolonged anesthesia during their early life (<3 year of age or during the third trimester of pregnancy of their mothers). Anesthetics may also cause significant deterioration in the cognitive functions of elderly patients. It is critically important for us to better understand the underlying mechanisms of anesthetic effects and related toxicities. My main research goal is to deepen our understanding of anesthetic mechanisms at the molecular level, in animal and human studies. We showed, using electrophysiological and molecular techniques, that anesthetics inhibit neurotransmitter release by interacting with neurotransmitter release machinery in neurons and chromaffin/PC-12 cells. Recently we found that drugs which elevate intracellular cAMP and/or block adenosine receptors could facilitate emergence from isoflurane and propofol anesthesia in rats. In a recent human trial, we reported that caffeine facilitates isoflurane anesthesia emergence in healthy volunteers. Our goal is to translate the current basic research findings to future clinical use in humans. Other ongoing studies involve anesthetic effects in autistic animal models and drugs which can reduce anesthetic induced neurotoxicity in the developing brain.
Xie Z, Currie KPM and Fox AP: Etomidate elevates intracellular calcium levels and promotes catecholamine secretion in bovine chromaffin cells. J Physiol. (London) 560.3: 677-690 2004. http://jp.physoc.org/content/560/3/677.full?sid=ef6f9266-c409-49ce-ae35-e3a638e97a56
Xie Z, Herring BE and Fox AP: Excitatory and inhibitory actions of isoflurane in bovine chromaffin cells. J Neurophysiol. 96: 3042-3050 2006. http://jn.physiology.org/cgi/reprint/00571.2006v1
Herring BE, Xie Z, Marks J and Fox AP : Isoflurane inhibits the neurotransmitter release machinery via an interaction with syntaxin 1A. J Neurophysiol. 102: 1265 – 1273, 2009. http://jn.physiology.org/cgi/reprint/102/2/1265.pdf
Herring BE, McMillan K, Fox AP and Xie Z: Etomidate and Propofol Inhibit The Neurotransmitter Release Machinery at Different Sites. J Physiol. (London) 589.5, 1103-1115, 2011. http://jp.physoc.org/content/589/5/1103.full.pdf+html?sid=19d7919e-d643-4b4e-9202-6bb6d51e015b.
Xie Z, McMillan K, Wang, Q and Fox, AP: Interaction of anesthetics with SNARE proteins identified with RNAi. J Neurophysiol. 109:758-767, 2013. http://jn.physiology.org/content/109/3/758.full.pdf+html?sid=9a365e95-6050-496e-8312-cd5d358cfbe1
Wang Q, Fong R, Mason P, Fox AP and Xie Z: Caffeine Accelerates Recovery from General Anesthesia. J Neurophysiol. 111: 1331-1340, 2014 http://jn.physiology.org/content/jn/111/6/1331.full.pdf