Inhalation anesthetic-induced neuronal damage in the developing rhesus monkey

Zou, Xiaoju; Liu, Fang; Zhang, Xuan; Patterson, Tucker A.; Callicott, Ralph; Liu, Shuliang; Hanig, Joseph P.; Paule, Merle G.; Slikker, William; Wang, Cheng

doi:10.1016/j.ntt.2011.06.003

Cited by 166 publications

(148 citation statements)

References 20 publications

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“…Nevertheless, all values for the cardinal physiological parameters including blood O 2 saturation level, body temperature, and blood glucose remained within normal ranges for both treated and control monkeys [20]. Generally, these data suggested that, in agreement with a previous study [7], the inhalational anesthetics induced-neurotoxicity is not associated with adverse physiological conditions including hypothermia, hypoxia, or hypoglycemia. The physiological parameters for both groups are summarized in Table 1.…”

Section: Physiological Responses To Inhaled Anesthetic Agentssupporting

confidence: 87%

“…In a parallel morphological study [7], PND 5, or 6 rhesus monkeys were exposed to N 2 O (70%) or ISO (1.0%) alone, or N 2 O plus ISO for 3 or 8 h, respectively. Inhalation of the combination of 70% N 2 O + 1% ISO produces a surgical plane of anesthesia.…”

Section: Discussionmentioning

confidence: 99%

“…To better understand the nature of inhalation anesthetic-induced neuronal damage monkey infants (PND 5 or 6) were randomly assigned in a parallel study [7] to treatment (n = 5; 1 male and 4 females) and control (n = 5; 2 males and 3 females) groups. Six hours after exposures were terminated, brain tissues were obtained for EM observations.…”

Section: Electron Microscopy (Em)mentioning

confidence: 99%

“…Because of the similarity of the physiology, pharmacology, metabolism, reproductive systems, and developmental trajectory and time course of the nonhuman primate to that of the human, they are exceptionally good animal models of neurodevelopment and for the detection of potential neurodegenerative effects associated with exposure to inhaled anesthetics. In a parallel study [7], a combination of 70% N 2 O + 1% ISO was also utilized to achieve and maintain a surgical plane of anesthesia. Neonatal rhesus monkeys were exposed on PND 5 or 6 to N 2 O plus ISO for 8 hours and 6 hours after termination of the exposure the brains were fixed and subsequently examined for neurotoxic effects.…”

Section: Introductionmentioning

confidence: 99%

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MicroPET/CT Imaging of [¹⁸F]-FEPPA in the Nonhuman Primate: A Potential Biomarker of Pathogenic Processes Associated with Anesthetic-Induced Neurotoxicity

Zhang

Paule

Newport

et al. 2012

ISRN Anesthesiology

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Background. The inhalation anesthetics nitrous oxide (N 2 O) and isoflurane (ISO) are used in surgical procedures for human infants. Injury to the central nervous system is often accompanied by localization of activated microglia or astrocytosis at the site of injury. The tracer that targets to the peripheral benzodiazepine receptor (PBR), [ 18 F]N-2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide ([ 18 F]-FEPPA), has been reported as a sensitive biomarker for the detection of neuronal damage/inflammation. Methods. On postnatal day (PND) 5 or 6 rhesus monkey neonates were exposed to a mixture of N 2 O/oxygen and ISO for 8 hours and control monkeys were exposed to room air. MicroPET/CT images with [ 18 F]-FEPPA were obtained for each monkey 1 day, one week, three weeks, and 6 months after the anesthetic exposure. Results. The radiotracer quickly distributed into the brains of both treated and control monkeys on all scan days. One day after anesthetic exposure, the uptake of [ 18 F]-FEPPA was significantly increased in the temporal lobe. One week after exposure, the uptake of [ 18 F]-FEPPA in the frontal lobe of treated animals was significantly greater than that in controls. Conclusions. These findings suggest that microPET imaging is capable of dynamic detection of inhaled anesthetic-induced brain damage in different brain regions of the nonhuman primate.

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Section: Physiological Responses To Inhaled Anesthetic Agentssupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Electron Microscopy (Em)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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MicroPET/CT Imaging of [¹⁸F]-FEPPA in the Nonhuman Primate: A Potential Biomarker of Pathogenic Processes Associated with Anesthetic-Induced Neurotoxicity

Zhang

Paule

Newport

et al. 2012

ISRN Anesthesiology

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“…Species differences can hinder the data's comparison with humans; therefore, the studies were widened to include the 6-day-old Macacus rhesus, which received isoflurane at a concentration of 3MAC for 5 hours. Advanced apoptosis was observed not only in the neurons but also in the glial cells when high concentrations of isoflurane were applied [35].…”

Section: Experimental Studiesmentioning

confidence: 99%

Czy rzeczywiście znany jest efekt farmakodynamiczny środków stosowanych podczas znieczulenia ogólnego u noworodków, niemowląt i dzieci? Przegląd eksperymentalnych i klinicznych badań dotyczących działania neurodegeneracyjnego

Bartkowska-Śniatkowska

Rosada-Kurasińska²,

Zielińska³

et al. 2014

Anaesthesiol Intensive Ther

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The practices of anaesthesiology and intensive therapy are difficult to imagine without sedation or general anaesthesia, regardless of whether the patient is a newborn, baby, child or adult. The relevant concerns for children are distinct from those for adults, primarily due to the effects of anatomical, physiological and pharmacokinetic-pharmacodynamic (PK/PD) differences, which become increasingly important in the brains of children as they develop. The process of central nervous system maturation in humans lasts for years, but its greatest activity (myelination and synaptogenesis) occurs during the fetal period and the first two years of life. Many experimental studies have demonstrated that exposure to anaesthetic drugs during this period can induce neurodegenerative changes in the central nervous systems of animals. The extrapolation of these results directly to humans must be performed with great caution, but anaesthesiologists around the world must begin to debate the safety of general anaesthesia in humans. Prospective trials should continue being carried out, and anaesthesia and surgery, delayed if possible among the smallest patients. The simultaneous use of different anaesthetics with the same potential neurotoxicities should also be avoided, potentially in favour of regional anaesthesia techniques, in this group of patients.

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Surgery and Neurodevelopmental Outcome of Very Low-Birth-Weight Infants

et al. 2014

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IMPORTANCE Reduced death and neurodevelopmental impairment among infants is a goal of perinatal medicine. OBJECTIVE To assess the association between surgery during the initial hospitalization and death or neurodevelopmental impairment of very low birth weight infants. DESIGN Retrospective cohort analysis of patients enrolled in the National Institute of Child Health and Human Development Neonatal Research Network Generic Database from 1998–2009 and evaluated at 18–22 months’ corrected age. SETTING 22 academic neonatal intensive care units. PARTICIPANTS Inclusion criteria were: birth weight 401–1500 g; survival to 12 hours; available for follow-up. Some conditions were excluded. 12 111 infants were included in analyses, 87% of those eligible. EXPOSURES Surgical procedures; surgery also classified by expected anesthesia type as major (general anesthesia) or minor surgery (non-general anesthesia). MAIN OUTCOME MEASURES Multivariable logistic regression analyses planned a priori were performed for the primary outcome of death or neurodevelopmental impairment and for the secondary outcome of neurodevelopmental impairment among survivors. Multivariable linear regression analyses were performed as planned for the adjusted means of Bayley Scales of Infant Development, Second Edition, Mental Developmental Index and Psychomotor Developmental Index for patients born before 2006. RESULTS There were 2186 major, 784 minor and 9141 no surgery patients. The risk-adjusted odds ratio of death or neurodevelopmental impairment for all surgery patients compared with those who had no surgery was 1.29 (95% confidence interval 1.08–1.55). For patients who had major surgery compared with those who had no surgery the risk-adjusted odds ratio of death or neurodevelopmental impairment was 1.52 (95% confidence interval 1.24–1.87). Patients classified as having minor surgery had no increased adjusted risk. Among survivors who had major surgery compared with those who had no surgery the adjusted odds ratio for neurodevelopmental impairment was 1.56 (95% confidence interval 1.26–1.93) and the adjusted mean Mental Developmental Index and mean Psychomotor Developmental Index values were lower. CONCLUSIONS AND RELEVANCE Major surgery in very low birth weight infants is independently associated with a greater than 50% increased risk of death or neurodevelopmental impairment and of neurodevelopmental impairment at 18–22 months’ corrected age. The role of general anesthesia is implicated but remains unproven.

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Inhalation anesthetic-induced neuronal damage in the developing rhesus monkey

Cited by 166 publications

References 20 publications

MicroPET/CT Imaging of [¹⁸F]-FEPPA in the Nonhuman Primate: A Potential Biomarker of Pathogenic Processes Associated with Anesthetic-Induced Neurotoxicity

MicroPET/CT Imaging of [¹⁸F]-FEPPA in the Nonhuman Primate: A Potential Biomarker of Pathogenic Processes Associated with Anesthetic-Induced Neurotoxicity

Czy rzeczywiście znany jest efekt farmakodynamiczny środków stosowanych podczas znieczulenia ogólnego u noworodków, niemowląt i dzieci? Przegląd eksperymentalnych i klinicznych badań dotyczących działania neurodegeneracyjnego

Surgery and Neurodevelopmental Outcome of Very Low-Birth-Weight Infants

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Inhalation anesthetic-induced neuronal damage in the developing rhesus monkey

Cited by 166 publications

References 20 publications

MicroPET/CT Imaging of [18F]-FEPPA in the Nonhuman Primate: A Potential Biomarker of Pathogenic Processes Associated with Anesthetic-Induced Neurotoxicity

MicroPET/CT Imaging of [18F]-FEPPA in the Nonhuman Primate: A Potential Biomarker of Pathogenic Processes Associated with Anesthetic-Induced Neurotoxicity

Czy rzeczywiście znany jest efekt farmakodynamiczny środków stosowanych podczas znieczulenia ogólnego u noworodków, niemowląt i dzieci? Przegląd eksperymentalnych i klinicznych badań dotyczących działania neurodegeneracyjnego

Surgery and Neurodevelopmental Outcome of Very Low-Birth-Weight Infants

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Product

Resources

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MicroPET/CT Imaging of [¹⁸F]-FEPPA in the Nonhuman Primate: A Potential Biomarker of Pathogenic Processes Associated with Anesthetic-Induced Neurotoxicity

MicroPET/CT Imaging of [¹⁸F]-FEPPA in the Nonhuman Primate: A Potential Biomarker of Pathogenic Processes Associated with Anesthetic-Induced Neurotoxicity