Anesthesia and Developing Brains: Unanswered Questions and Proposed Paths Forward

2022 ◽  
Author(s):  
Caleb Ing ◽  
David O. Warner ◽  
Lena S. Sun ◽  
Randall P. Flick ◽  
Andrew J. Davidson ◽  
...  
Keyword(s):  
Animal Models ◽  
Clinical Research ◽  
Nonhuman Primates ◽  
Clinical Evidence ◽  
Behavioral Changes ◽  
Neurodevelopmental Outcomes ◽  
Behavioral Deficits ◽  
Anesthetic Agents ◽  
Anesthetic Exposure ◽  
Intense Debate

Anesthetic agents disrupt neurodevelopment in animal models, but evidence in humans is mixed. The morphologic and behavioral changes observed across many species predicted that deficits should be seen in humans, but identifying a phenotype of injury in children has been challenging. It is increasingly clear that in children, a brief or single early anesthetic exposure is not associated with deficits in a range of neurodevelopmental outcomes including broad measures of intelligence. Deficits in other domains including behavior, however, are more consistently reported in humans and also reflect findings from nonhuman primates. The possibility that behavioral deficits are a phenotype, as well as the entire concept of anesthetic neurotoxicity in children, remains a source of intense debate. The purpose of this report is to describe consensus and disagreement among experts, summarize preclinical and clinical evidence, suggest pathways for future clinical research, and compare studies of anesthetic agents to other suspected neurotoxins.

Impact of surgery timing for craniosynostosis on neurodevelopmental outcomes: a systematic review

2019 ◽  
Vol 23 (4) ◽  
pp. 442-454 ◽  
Author(s):  
Rachel Mandela ◽  
Maggie Bellew ◽  
Paul Chumas ◽  
Hannah Nash
Keyword(s):  
Systematic Review ◽  
Beneficial Effect ◽  
Data Extraction ◽  
Sociodemographic Factors ◽  
Future Research ◽  
Neurodevelopmental Outcomes ◽  
Age At Surgery ◽  
Data Extraction Form ◽  
Surgery Timing ◽  
Anesthetic Exposure

OBJECTIVEThere are currently no guidelines for the optimum age for surgical treatment of craniosynostosis. This systematic review summarizes and assesses evidence on whether there is an optimal age for surgery in terms of neurodevelopmental outcomes.METHODSThe databases MEDLINE, PsycINFO, CINAHL, Embase + Embase Classic, and Web of Science were searched between October and November 2016 and searches were repeated in July 2017. According to PICO (participants, intervention, comparison, outcome) criteria, studies were included that focused on: children diagnosed with nonsyndromic craniosynostosis, aged ≤ 5 years at time of surgery; corrective surgery for nonsyndromic craniosynostosis; comparison of age-at-surgery groups; and tests of cognitive and neurodevelopmental postoperative outcomes. Studies that did not compare age-at-surgery groups (e.g., those employing a correlational design alone) were excluded. Data were double-extracted by 2 authors using a modified version of the Cochrane data extraction form.RESULTSTen studies met the specified criteria; 5 found a beneficial effect of earlier surgery, and 5 did not. No study found a beneficial effect of later surgery. No study collected data on length of anesthetic exposure and only 1 study collected data on sociodemographic factors.CONCLUSIONSIt was difficult to draw firm conclusions from the results due to multiple confounding factors. There is some inconclusive evidence that earlier surgery is beneficial for patients with sagittal synostosis. The picture is even more mixed for other subtypes. There is no evidence that later surgery is beneficial. The authors recommend that future research use agreed-upon parameters for: age-at-surgery cut-offs, follow-up times, and outcome measures.

scholarly journals Foraging with the frontal cortex: A cross-species evaluation of reward-guided behavior

2021 ◽  
Author(s):  
Peter H. Rudebeck ◽  
Alicia Izquierdo
Keyword(s):  
Animal Models ◽  
Frontal Cortex ◽  
Psychiatric Disorders ◽  
Similarities And Differences ◽  
And Function ◽  
Future Work ◽  
Intense Debate

AbstractEfficient foraging is essential to survival and depends on frontal cortex in mammals. Because of its role in psychiatric disorders, frontal cortex and its contributions to reward procurement have been studied extensively in both rodents and non-human primates. How frontal cortex of these animal models compares is a source of intense debate. Here we argue that translating findings from rodents to non-human primates requires an appreciation of both the niche in which each animal forages as well as the similarities in frontal cortex anatomy and function. Consequently, we highlight similarities and differences in behavior and anatomy, before focusing on points of convergence in how parts of frontal cortex contribute to distinct aspects of foraging in rats and macaques, more specifically. In doing so, our aim is to emphasize where translation of frontal cortex function between species is clearer, where there is divergence, and where future work should focus. We finish by highlighting aspects of foraging for which have received less attention but we believe are critical to uncovering how frontal cortex promotes survival in each species.

scholarly journals The effect of a nighttime zoo event on spider monkey (Ateles geoffroyi) behavior

2020 ◽  
Vol 1 ◽  
Author(s):  
Darby Proctor ◽  
Michelle Smurl
Keyword(s):  
Nonhuman Primates ◽  
Environmental Changes ◽  
Behavioral Changes ◽  
Physiological Data ◽  
Spider Monkeys ◽  
Normal Operating ◽  
Late Night ◽  
Behavioral Observations ◽  
Zoo Animals ◽  
The Relationship

Abstract The relationship between zoo animals, particularly nonhuman primates, and visitors is complex and varies by species. Adding complexity to this relationship is the trend for zoos to host events outside of normal operating hours. Here, we explored whether a late-night haunted-house style event influenced the behavior of spider monkeys. We conducted behavioral observations both on event nights and nights without the event. The spider monkeys were active and outside more frequently on event nights compared to the control nights indicating that their typical nighttime behavior was altered. However, it is difficult to definitively conclude whether the behavioral changes were a result of the event being aversive or enriching. Our findings suggest that zoos should conduct behavioral observations of and collect physiological data from their animals, especially if they are sensitive to environmental changes, when implementing new events, including those occurring outside of normal operating hours to ensure high levels of animal welfare.

scholarly journals Monkey Models of Tuberculosis: Lessons Learned

2014 ◽  
Vol 83 (3) ◽  
pp. 852-862 ◽  
Author(s):  
Juliet C. Peña ◽  
Wen-Zhe Ho
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Animal Models ◽  
Nonhuman Primates ◽  
Lessons Learned ◽  
Preclinical Testing ◽  
Content Type ◽  
Cynomolgus Macaques ◽  
Drug Regimens

The use of animal models has been invaluable for studying the pathogenesis ofMycobacterium tuberculosisinfection, as well as for testing the efficacy of vaccines and drug regimens for tuberculosis. Among the applied animal models, nonhuman primates, particularly macaques, share the greatest anatomical and physiological similarities with humans. As such, macaque models have been used for investigating tuberculosis pathogenesis and preclinical testing of drugs and vaccines. This review focuses on published major studies which illustrate how the rhesus and cynomolgus macaques have enriched and may continue to advance the field of global tuberculosis research.

Post-Traumatic Stress Disorder

2020 ◽  
pp. 433-464
Author(s):  
Richard McCarty
Keyword(s):  
Animal Models ◽  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Stress Disorder ◽  
Behavioral Changes ◽  
Laboratory Animals ◽  
Nasal Administration ◽  
Post Traumatic Stress ◽  
Laboratory Rats ◽  
Post Traumatic

Two especially valuable animal models of post-traumatic stress disorder (PTSD) have been developed, including brief exposure of laboratory rats to a predator (a cat) or its odor, and the single prolonged stress paradigm. In each of these models, laboratory animals are evaluated for behavioral changes several days to several weeks following the stressful experience and are compared to unstressed controls. In both of these models, stressed animals display behavioral changes consistent with a PTSD-like phenotype. Using these models, investigators have explored central and peripheral neural and endocrine changes associated with the onset of PTSD-like symptoms and approaches to prevent or block the effects of the traumatic stressor on behavioral changes. Two particularly effective treatments that have been described include administration of a protein synthesis inhibitor and intra-nasal administration of neuropeptide Y. Animal models also provide an opportunity to study transgenerational transmission of PTSD risk.

scholarly journals Use of Prescribed Psychotropics during Pregnancy: A Systematic Review of Pregnancy, Neonatal, and Childhood Outcomes

2019 ◽  
Vol 9 (9) ◽  
pp. 235 ◽  
Author(s):  
Creeley ◽  
Denton
Keyword(s):  
Public Health ◽  
Mental Health ◽  
Mental Illness ◽  
Clinical Research ◽  
Prenatal Exposure ◽  
Psychotropic Drugs ◽  
Health Concern ◽  
Neurodevelopmental Outcomes ◽  
Mother And Child

This paper reviews the findings from preclinical animal and human clinical research investigating maternal/fetal, neonatal, and child neurodevelopmental outcomes following prenatal exposure to psychotropic drugs. Evidence for the risks associated with prenatal exposure was examined, including teratogenicity, neurodevelopmental effects, neonatal toxicity, and long-term neurobehavioral consequences (i.e., behavioral teratogenicity). We conducted a comprehensive review of the recent results and conclusions of original research and reviews, respectively, which have investigated the short- and long-term impact of drugs commonly prescribed to pregnant women for psychological disorders, including mood, anxiety, and sleep disorders. Because mental illness in the mother is not a benign event, and may itself pose significant risks to both mother and child, simply discontinuing or avoiding medication use during pregnancy may not be possible. Therefore, prenatal exposure to psychotropic drugs is a major public health concern. Decisions regarding drug choice, dose, and duration should be made carefully, by balancing severity, chronicity, and co-morbidity of the mental illness, disorder, or condition against the potential risk for adverse outcomes due to drug exposure. Globally, maternal mental health problems are considered as a major public health challenge, which requires a stronger focus on mental health services that will benefit both mother and child. More preclinical and clinical research is needed in order to make well-informed decisions, understanding the risks associated with the use of psychotropic medications during pregnancy.

scholarly journals Coxiella burnetii Intratracheal Aerosol Infection Model in Mice, Guinea Pigs, and Nonhuman Primates

2019 ◽  
Vol 87 (12) ◽  
Author(s):  
A. E. Gregory ◽  
E. J. van Schaik ◽  
K. E. Russell-Lodrigue ◽  
A. P. Fratzke ◽  
J. E. Samuel
Keyword(s):  
Animal Models ◽  
Coxiella Burnetii ◽  
Guinea Pigs ◽  
Nonhuman Primates ◽  
Q Fever ◽  
Febrile Illness ◽  
Cell Vaccine ◽  
Infection Model ◽  
Atypical Pneumonia ◽  
Content Type

ABSTRACT Coxiella burnetii, the etiological agent of Q fever, is a Gram-negative bacterium transmitted to humans by inhalation of contaminated aerosols. Acute Q fever is often self-limiting, presenting as a febrile illness that can result in atypical pneumonia. In some cases, Q fever becomes chronic, leading to endocarditis that can be life threatening. The formalin-inactivated whole-cell vaccine (WCV) confers long-term protection but has significant side effects when administered to presensitized individuals. Designing new vaccines against C. burnetii remains a challenge and requires the use of clinically relevant modes of transmission in appropriate animal models. We have developed a safe and reproducible C. burnetii aerosol challenge in three different animal models to evaluate the effects of pulmonary acquired infection. Using a MicroSprayer aerosolizer, BL/6 mice and Hartley guinea pigs were infected intratracheally with C. burnetii Nine Mile phase I (NMI) and demonstrated susceptibility as determined by measuring bacterial growth in the lungs and subsequent dissemination to the spleen. Histological analysis of lung tissue showed significant pathology associated with disease, which was more severe in guinea pigs. Infection using large-particle aerosol (LPA) delivery was further confirmed in nonhuman primates, which developed fever and pneumonia. We also demonstrate that vaccinating mice and guinea pigs with WCV prior to LPA challenge is capable of eliciting protective immunity that significantly reduces splenomegaly and the bacterial burden in spleen and lung tissues. These data suggest that these models can have appreciable value in using the LPA delivery system to study pulmonary Q fever pathogenesis as well as designing vaccine countermeasures to C. burnetii aerosol transmission.

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