Anesthetics and sedatives: toxic or protective for the developing brain?
ABSTRACT Despite our insufficient understanding of the exact molecular mechanisms of general anesthetics and sedatives, every year millions of children are treated with these drugs in a seemingly safe manner. However, increasing evidence particularly from animal studies has suggested the possibility for deleterious effects in pediatric patients. All currently clinically utilized anesthetic drugs have been found to induce neuronal cell death in the developing brain and to potentially cause long-term neurological impairment. Conversely, painful stimuli without analgesia and anesthesia have also been shown to initiate a harmful stress response in young children and to trigger neurotoxic effects in the developing brain, which can be blunted by anesthetics. Moreover, anesthetic drugs may also confer neurological protection during hypoxic and ischemic insults. The mechanisms and human applicability of anesthetic neurotoxicity and neuroprotection remain under intense investigation and this Perspectives article summarizes the current state of research.
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ABSTRACT: Neural progenitor cell expansion is critical for normal brain development and an appropriate response to injury. During the brain growth spurt, exposures to general anesthetics, which either block the N-methyl-d-aspartate receptor or enhance the γ-aminobutyric acid receptor type A can disturb neuronal transduction. This effect can be detrimental to brain development. Until now, the effects of anesthetic exposure on neural progenitor cell expansion in vivo had seldom been reported. Here, minimally invasive micro positron emission tomography (microPET) coupled with 3'-deoxy-3' [(18)F] fluoro-l-thymidine ([(18)F]FLT) was utilized to assess the effects of sevoflurane exposure on neural progenitor cell proliferation. FLT, a thymidine analog, is taken up by proliferating cells and phosphorylated in the cytoplasm, leading to its intracellular trapping. Intracellular retention of [(18)F]FLT, thus, represents an observable in vivo marker of cell proliferation. Here, postnatal day 7 rats (n = 11/group) were exposed to 2.5% sevoflurane or room air for 9 h. For up to 2 weeks following the exposure, standard uptake values (SUVs) for [(18)F]-FLT in the hippocampal formation were significantly attenuated in the sevoflurane-exposed rats (p < 0.0001), suggesting decreased uptake and retention of [(18)F]FLT (decreased proliferation) in these regions. Four weeks following exposure, SUVs for [(18)F]FLT were comparable in the sevoflurane-exposed rats and in controls. Co-administration of 7-nitroindazole (30 mg/kg, n = 5), a selective inhibitor of neuronal nitric oxide synthase, significantly attenuated the SUVs for [(18)F]FLT in both the air-exposed (p = 0.00006) and sevoflurane-exposed rats (p = 0.0427) in the first week following the exposure. These findings suggested that microPET in couple with [(18)F]FLT as cell proliferation marker could be used as a non-invasive modality to monitor the sevoflurane-induced inhibition of neural progenitor cell proliferation in vivo.Frontiers in Neurology 11/2014; 5:234.
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ABSTRACT: Introduction: Several experimental and clinical studies suggest that drugs used in pediatric anesthesia may exert undesirable effects on the developing central nervous system. The objective of this review was to assess the results and conclusions of published studies on long lasting neurodevelopment disorders following exposure to anesthetics in children in a phase of brain immaturity. Material and Methods: We performed a literature search in several sources (PubMed, SciELO and Cochrane Library) using the terms 'Pediatric anesthesia OR Pediatric anesthetic OR Developing brain anesthetic OR Developing brain anesthesia AND behavior disorders'. We selected human studies, referring to long lasting neurodevelopment effects after exposure to anesthetics in the first four years of life. Results: Ten retrospective studies met the inclusion criteria. Of these, seven suggest risk of neurobehavioral disorders after exposure of small children to anesthetics, as opposed to the results obtained by the other three. Discussion: Although mostly using large databases, the studies found are retrospective, vary in test groups, include sometimes avoidable confounders and some present inaccuracies in the choice of the test and control populations that can compromise the reliability of the results. Conclusion: Because of the numerous limitations of the few studies available, the reported results are still deemed insufficient to change current clinical practice. However, although it is undisputable that anesthesia should be provided when needed, regardless of age, the warnings found in literature are worrisome, therefore whenever surgery is unavoidable in small children, alternatives that may help reduce the risks of anesthetic exposure should be sought.Acta medica portuguesa. 05/2014; 27(3):383-389.
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ABSTRACT: This article reviews the pertinent perioperative, intraoperative, and short- and long-term postoperative risks associated with general anesthesia in children undergoing ocular surgery.Current Opinion in Ophthalmology 07/2014; · 2.64 Impact Factor