Nathalie Percie du Sert

• PhD
• Head of Experimental Design and Reporting at National Centre for the Replacement, Refinement and Reduction of Animals in Research

Neuropathic pain remains an area of considerable unmet clinical need. Research based on preclinical animal models has failed to deliver truly novel treatment options, questioning the predictive value of these models. This review addresses the shortcomings of rodent in vivo models commonly used in the field and highlights approaches which could incr...

Many factors can influence the outcome and interpretation of experiments using animals – from the strain or sex of the animal through to choosing the correct statistical method for analysis. You would therefore expect such information to be readily available in all publications reporting in vivo

The ferret cisplatin emesis model has been used for ~30 years and enabled identification of clinically used anti-emetics. We provide an objective assessment of this model including efficacy of 5-HT₃ receptor antagonists to assess its translational validity. A systematic review identified available evidence and was used to perform meta-analyses. Of...

Emesis is a multi-system reflex, which is usually investigated using in vivo models. The aim of the study is to compare the response induced by emetic compounds across species and investigate whether dogs, ferrets and rats are all similarly predictive of humans. A systematic review was carried out and relevant publications were identified from PubM...

A new, interactive framework supports the evaluation of in vivo and ex vivo research proposals from a sex inclusive research perspective delivering a traffic light classification, indicating whether a proposal is appropriate, risky, or insufficient with regards to sex inclusion. This tool is designed for use by researchers, (animal) ethical review...

In animal experiments, blinding (also known as masking) is a methodological strategy to reduce the risk that scientists, animal care staff, or other staff involved in the research may consciously or subconsciously influence the outcome. Lack of masking has been shown to correlate with an overestimation of treatment efficacy and false positive findi...

Throughout the global coronavirus pandemic, we have seen an unprecedented volume of COVID-19 researchpublications. This vast body of evidence continues to grow, making it difficult for research users to keep up with the pace of evolving research findings. To enable the synthesis of this evidence for timely use by researchers, policymakers, and othe...

Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work ade...

Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work ade...

Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work ade...

Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work ade...

Improving the reproducibility of biomedical research is a major challenge. Transparent and accurate reporting is vital to this process; it allows readers to assess the reliability of the findings and repeat or build upon the work of other researchers. The ARRIVE guidelines (Animal Research: Reporting In Vivo Experiments) were developed in 2010 to h...

Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work ade...

Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work ade...

Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work ade...

Koroshetz et al. There is a pressing need to increase the rigor of research in the life and biomedical sciences. To address this issue, we propose that communities of ’rigor champions’ be established to campaign for reforms of the research culture that has led to shortcomings in rigor. These communities of rigor champions would also assist in the d...

Preclinical studies using animals to study the potential of a therapeutic drug or strategy are important steps before translation to clinical trials. However, evidence has shown that poor quality in the design and conduct of these studies has not only impeded clinical translation but also led to significant waste of valuable research resources. It...

Improving the reproducibility of biomedical research is a major challenge. Transparent and accurate reporting are vital to this process; it allows readers to assess the reliability of the findings, and repeat or build upon the work of other researchers. The NC3Rs developed the ARRIVE guidelines in 2010 to help authors and journals identify the mini...

Reproducible science requires transparent reporting. The ARRIVE guidelines were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and rep...

In 2010, the NC3Rs published the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines to improve the reporting of animal research. Despite considerable levels of support from the scientific community, the impact on the quality of reporting in animal research publications has been limited. This position paper highlights the strategy...

This editorial introduces the NC3Rs gateway, which publishes articles and reviews on new models and technologies emerging from NC3Rs-funded research. The aim is to raise awareness about these approaches, increase confidence in their capability, and provide sufficient information to facilitate their uptake by others.

Addressing the common problems that researchers encounter when designing and analysing animal experiments will improve the reliability of in vivo research. In this article, the Experimental Design Assistant (EDA) is introduced. The EDA is a web-based tool that guides the in vivo researcher through the experimental design and analysis process, provi...

Most in vivo models of ischaemic stroke target the middle cerebral artery and a spectrum of stroke severities, from mild to substantial, can be achieved. This review describes opportunities to improve the in vivo modelling of ischaemic stroke and animal welfare. It provides a number of recommendations to minimise the level of severity in the most c...

Improving the reliability and efficiency of scientific research will increase the credibility of the published scientific literature and accelerate discovery. Here we argue for the adoption of measures to optimize key elements of the scientific process: methods, reporting and dissemination, reproducibility, evaluation and incentives. There is some...

Cisplatin (cis-dichlorodiammineplatinum(II)), is an anti-cancer chemotherapeutic agent; it is a highly emetogenic compound and induces emesis typically divided into acute and delayed phases. Despite major advances in anti-emetic research, the control of vomiting and especially nausea is still sub-optimal. Biomarkers, which temporally correlate with...

Background Rodents are incapable of emesis and consequently the emetic potential of glucagon-like peptide-1 receptor (GLP-1R) agonists in studies designed to assess a potential blood glucose lowering action of the compound was missed. Therefore, we investigated if the ferret, a carnivore with demonstrated translation capability in emesis research,...

This chapter discusses the evolution of the use of ferrets for studies of nausea and vomiting primarily from a biological perspective. The introduction of highly emetic but potentially curative therapies stimulated controlled clinical trials of current antiemetics and stimulated interest in understanding the mechanism by which the agents induced em...

Dictyostelium chemotaxis was monitored by time-lapse photography to record cells moving within a Dunn Chamber towards the chemo-attractant, cAMP, across the screen from bottom right to top left. Images were taken every 6 seconds over a 15 minute period. Computer generated cell outlines enables average cell velocity, shape and direction of movement...

Homology search results (BLAST analysis) of the Dictyostelium genome for proteins showing amino acid similarity to TRPV receptors from multiple species. Potential homologues are defined by an E-value of less than 1.00E-40 [11], thus Dictyostelium does not contain proteins showing significant sequence similarity to be considered as homologues. (DOCX...

Homology search results (BLAST analysis) of the Dictyostelium genome for proteins showing amino acid similarity to TRPM5 receptors from human and mouse. Potential homologues are defined by an E-value of less than 1.00E-40 [11], thus Dictyostelium does not contain proteins showing significant sequence similarity to be considered as homologues. N/A =...

Dictyostelium chemotaxis was monitored by time-lapse photography to record cells moving within a Dunn Chamber towards the chemo-attractant, cAMP, across the screen from left to right. Images were taken every 6 seconds over a 15 minute period. Computer generated cell outlines enables average cell velocity, shape and direction of movement to be quant...

Homology search results (BLAST analysis) of the Dictyostelium genome for proteins showing amino acid similarity to known bitter receptors from multiple species. Potential homologues are defined by an E-value of less than 1.00E-40 [11], thus Dictyostelium does not contain proteins showing significant sequence similarity to be considered as homologue...

Novel chemical entities (NCEs) may be investigated for emetic liability in a range of unpleasant experiments involving retching, vomiting or conditioned taste aversion/food avoidance in sentient animals. We have used a range of compounds with known emetic /aversive properties to examine the possibility of using the social amoeba, Dictyostelium disc...

The gastric myoelectric activity (GMA) is the electrical pacesetter potential, which drives gastric motility. Cannabinoids have broad-spectrum antiemetic and antinauseant activity. Paradoxically, they inhibit intestinal peristalsis and reduce gastric motility but their effect on GMA remains unknown. Ferrets were surgically implanted with radiotelem...

In humans, motion sickness is associated with disruption of normal gastric myoelectric activity, and it has been proposed that this results from an imbalance of autonomic nervous system activity. We used the established Suncus murinus (house musk shrew) model of motion-induced emesis to investigate the effect of horizontal motion on gastric myoelec...

To characterize the gastric myoelectric activity (GMA) and intra-abdominal pressure changes induced by emetic stimuli (apomorphine and cisplatin) in the ferret. GMA and intra-abdominal pressure were recorded in conscious, unrestrained ferrets surgically implanted with radiotelemetry transmitters. Animals were challenged with apomorphine (0.25 mg/kg...

Pungent transient receptor potential vanilloid (TRPV1) channel activators have been shown to have broad inhibitory anti-emetic activity against centrally- and peripherally acting challenges but only at doses that have adverse effects on the cardiovascular system and on temperature homeostasis. In the present studies, we investigated the anti-emetic...

The anti-cancer chemotherapeutic agent cisplatin induces an acute (approximately 24 h) and delayed (approximately 24-72 h+) emetic response in humans; whereas the mechanism mediating the acute phase has been characterised, the delayed phase is relatively poorly understood. We have used nerve lesions (abdominal vagus, VX; greater splanchnic nerve, G...

Anti-emetic drugs such as the tachykinin NK(1) receptor antagonists are useful to control emesis induced by diverse challenges. Evidence suggests pungent capsaicin-like TRPV1 activators also have broad inhibitory anti-emetic activity. However, pungent compounds are associated with undesirable effects including adverse actions on the cardiovascular...