Brain sciences
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Anesthetic neurotoxicity has been a hot topic in anesthesia for the past decade. It is of special interest to pediatric anesthesiologists. A subgroup of children potentially at greater risk for anesthetic neurotoxicity, based on a prolonged anesthetic exposure early in development, are those children receiving anesthesia for surgical repair of congenital heart disease. ⋯ These children not only receive prolonged anesthetic exposure during surgical repair, but also receive repeated anesthetic exposures during a critical period of brain development. Their propensity to abnormal brain development, as a result of congenital heart disease, may modify their risk of anesthetic neurotoxicity. This review article provides an overview of anesthetic neurotoxicity from the perspective of a pediatric cardiac anesthesiologist and provides insight into basic science and clinical investigations as it relates to this unique group of children who have been studied over several decades for their risk of neurologic injury.
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The inhalation anesthetic isoflurane has been reported to induce caspase activation and apoptosis, which may lead to learning and memory impairment. However, the underlying mechanisms of these effects are largely unknown. Isoflurane has been shown to induce elevation of cytosol calcium levels, accumulation of reactive oxygen species (ROS), opening of the mitochondrial permeability transition pore, reduction in mitochondria membrane potential, and release of cytochrome c. ⋯ These data illustrated that isoflurane could cause time-dependent effects on ROS levels. These findings have established a system to further determine the time course effects of isoflurane on cellular and mitochondria function. Ultimately, the studies would elucidate, at least partially, the underlying mechanisms of isoflurane-induced cellular toxicity.
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Propofol is a general anesthetic widely used in surgical procedures, including those in pregnant women. Preclinical studies suggest that propofol may cause neuronal injury to the offspring of primates if it is administered during pregnancy. However, it is unknown whether those neuronal changes would lead to long-term behavioral deficits in the offspring. ⋯ Furthermore, exploratory and learning behaviors of offspring rats (started at P28) were assessed in open-field trial and eight-arm radial maze. The offspring from propofol-treated dams showed significantly less exploratory activity in the open-field test and less spatial learning in the eight-arm radial maze. Thus, this study suggested that propofol exposure during pregnancy in rat increased cleaved caspsase-3 levels in fetal brain, deletion of neurons, reduced synaptophysin levels in the hippocampal region, and persistent learning deficits in the offspring.
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The use of volatile anesthetics, a group of general anesthetics, is an exceedingly common practice. These anesthetics may have neuroprotective effects. Over the last decade, anesthetic induced neurotoxicity in pediatric populations has gained a certain notoriety based on pre-clinical cell and animal studies demonstrating that general anesthetics may induce neurotoxicity, including neuroapoptosis, neurodegeneration, and long-term neurocognitive and behavioral deficits. ⋯ Thus far, very few clinical studies exist, and have not yet been convincing enough to alter our practice. This review will provide an update on current data regarding volatile anesthetic induced neurotoxicity and neuroprotection in neonatal and infant populations. In addition, this paper will discuss ongoing studies and the trajectory of further research over the coming years.
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Over the past decade, scientific discoveries have highlighted new roles for a unique class of non-coding RNAs. Transcribed from the genome, these non-coding RNAs have been implicated in determining the biological complexity seen in mammals by acting as transcriptional and translational regulators. Non-coding RNAs, which can be sub-classified into long non-coding RNAs, microRNAs, PIWI-interacting RNAs and several others, are widely expressed in the nervous system with roles in neurogenesis, development and maintenance of the neuronal phenotype. ⋯ A better understanding of their expression patterns and functions has uncovered the potential use of these riboregulators as neuroprotectants to antagonize the detrimental molecular events taking place upon ischemic-reperfusion injury. In this review, we discuss the various roles of non-coding RNAs in brain development and their mechanisms of gene regulation in relation to ischemic brain injury. We will also address the future directions and open questions for identifying promising non-coding RNAs that could eventually serve as potential neuroprotectants against ischemic brain injury.