Abstract
Since its invention, general anesthesia has been an indispensable component of modern surgery. While traditionally considered safe and beneficial in many pathological settings, hundreds of preclinical studies in various animal species have raised concerns about the detrimental and long-lasting consequences that general anesthetics may cause to the developing brain. Clinical evidence of anesthetic neurotoxicity in humans continues to mount as we continue to contemplate how to move forward. Notwithstanding the alarming evidence, millions of children are being anesthetized each year, setting the stage for substantial healthcare burdens in the future. Hence, furthering our knowledge of the molecular underpinnings of anesthesia-induced developmental neurotoxicity is crucially important and should enable us to develop protective strategies so that currently available general anesthetics could be safely used during critical stages of brain development. In this mini-review, we provide a summary of select strategies with primary focus on the mechanisms of neuroprotection and potential for clinical applicability. First, we summarize a diverse group of chemicals with the emphasis on intracellular targets and signal-transduction pathways. We then discuss epigenetic and transgenerational effects of general anesthetics and potential remedies, and also anesthesia-sparing or anesthesia-delaying approaches. Finally, we present evidence of a novel class of anesthetics with a distinct mechanism of action and a promising safety profile.
Highlights
Since its invention in the mid-nineteenth century, general anesthesia (GA) has been an indispensable component of surgical procedures
How do we address these growing concerns that GA may pose a substantial healthcare burden in years to come considering that millions of children are being anesthetized every year? Over the past several decades a considerable effort has been made to devise neuroprotective strategies that would enable the use of currently available GAs while avoiding their unwanted neurotoxic effects
Dexmedetomidine reversed neurotoxic effects of general anesthetics via modulation of the PI3K/Akt pathway; i.e., the Phosphorylated Akt (pAkt) level was increased [56,57] while GSK-3β was phosphorylated and inactivated [56]
Summary
Since its invention in the mid-nineteenth century, general anesthesia (GA) has been an indispensable component of surgical procedures. Preclinical evidence is overwhelming—the notion that GA causes detrimental and long-lasting injury to the developing brain has been confirmed by hundreds of preclinical studies in numerous animal species [1,2,3,4,5,6,7,8,9,10]. Over the past several decades a considerable effort has been made to devise neuroprotective strategies that would enable the use of currently available GAs while avoiding their unwanted neurotoxic effects. Based on our present knowledge of the cellular pathways that play a role in neuronal and glial demise, we and others have reported many different approaches using numerous compounds that were introduced with a goal to control, prevent or protect against the deleterious effects of GAs. far, there are hundreds of preclinical studies that have examined different types of neuroprotective strategies. We provide a summary of select strategic approaches with a primary focus on different mechanisms of neuroprotection and potential clinical applicability
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