Neurochemical effects of anesthetic agents: implications for toxicity, addiction and cognitive dysfunction

A recent Op Ed in the New York Times (February 23, 2013, David Engleman) aptly summarized the complexity of the human brain. «The Brain is composed of ~86 billion electrically active neurons, each connected to many thousands of neighbors. Each neuron relays information in the form of miniature voltage spikes, which are then converted into chemical signals that bridge the gap to other neurons. Most neurons send these signals many times per second. The complexity of such a system bankrupts our language; with our current technologies, we mostly detect an enigmatic uproar.» «A new kind of science is required, one that can track and analyze the activity of billions of neurons simultaneously.» Thus, the Obama administration’s support for study of functional connectivity in the human brain. This represents the new paradigm for brain function in our century. The paradigm shift responsible for the current broadening of interest for Anesthesiologists in the many neurological consequences of all of the cellular and subcellular effects of anesthetic agents is well discussed by Perouansky and by Ginosar and Binshtok in editorial comments on this article. (Perouansky M. «The Quest for a Unifi ed Model of Anesthetic Action: A Century in Claude Bernard’s Shadow.» Anesthesiology 2012;117:465-74) Perouansky suggests that we have been in thrall to Claude Bernard for the last century, trapped in a paradigm demanding a single mode of action to anesthetic agents, ignoring their protean effects on many aspects of cellular and enzymatic function. Franks and Lieb’s(1) seminal observations of volatile anesthetic effects on protein, at hydrophobic lipophilic and other molecular binding sites, has allowed us to move from the prior focus on lipid membrane effects of these agents, opening our minds to the multitude of actions of these agents on enzymes, on cellular function and on neurochemistry. It is the intention in this lecture to outline aspects of recent work in neurochemistry and anesthesia, the implications for neurotoxicity, the involvement in addiction mechanisms, and in genesis of delirium and cognitive dysfunction.