Lasting effects of general anesthetics on the brain in the young and elderly: “mixed picture” of neurotoxicity, neuroprotection and cognitive impairment

Abstract

General anesthetics are commonly used in major surgery. To achieve the depth of anesthesia for surgery, patients are being subjected to a variety of general anesthetics, alone or in combination. It has been long held an illusory concept that the general anesthesia is entirely reversible and that the central nervous system is returned to its pristine state once the anesthetic agent is eliminated from the active site. However, studies indicate that perturbation of the normal functioning of these targets may result in long-lasting desirable or undesirable effects. This review focuses on the impact of general anesthetic exposure to the brain and summarizes the molecular and cellular mechanisms by which general anesthetics may induce long-lasting undesirable effects when exposed at the developing stage of the brain. The vulnerability of aging brain to general anesthetics, specifically in the context of cognitive disorders and Alzheimer’s disease pathogeneses are also discussed. Moreover, we will review emerging evidence regarding the neuroprotective property of xenon and anesthetic adjuvant dexmedetomidine in the immature and mature brains. In conclusion, “mixed picture” effects of general anesthetics should be well acknowledged and should be implemented into daily clinical practice for better patient outcome.

General anesthesia affecting on developing brain: evidence from animal to clinical research

“…It is more appropriate for a range of studies to examine a range of outcomes, anaesthetic duration and age at exposure. Many elaborate reviews on this topic have been published recently and assessed most of the clinical studies [3,[28][29][30][31]. In this review, we will briefly summarize the upto-date and the most well designed three clinical studies and discuss the limitations.…”

Conflicting Actions of Inhalational Anesthetics, Neurotoxicity and Neuroprotection, Mediated by the Unfolded Protein Response

“…Exposure to sevoflurane has also been shown to improve cognitive function in both young (8-10 weeks) and aged rats (19 months) [13]. The general mechanism responsible for these conflicting effects, neurotoxicity and neuroprotection, remains unelucidated [14][15][16].…”

Training in pediatric anesthesia in Japan: how should we come along?

“…The potential long-term impact of surgery and anesthesia has been progressing over the past 20 years with a significant interest and academically challenging research activity on the several aspects of neurodevelopment [1,2]. Although anesthesiologists are currently facing the likelihood that detectable developmental anesthetic neurotoxicity may not exist in a single and short exposure to general anesthesia in early life [3][4][5][6], they have not yet been able to prove or disprove this nonexistence [7].…”