Opportunities for improving animal welfare in rodent models of epilepsy and seizures

Animal models of epilepsy and seizures, mostly involving mice and rats, are used to understand the pathophysiology of the different forms of epilepsy and their comorbidities, to identify biomarkers, and to discover new antiepileptic drugs and treatments for comorbidities. Such models represent an important area for application of the 3Rs (replacement, reduction and refinement of animal use). This report provides background information and recommendations aimed at minimising pain, suffering and distress in rodent models of epilepsy and seizures in order to improve animal welfare and optimise the quality of studies in this area. The report includes practical guidance on principles of choosing a model, induction procedures, in vivo recordings, perioperative care, welfare assessment, humane endpoints, social housing, environmental enrichment, reporting of studies and data sharing. In addition, some model-specific welfare considerations are discussed, and data gaps and areas for further research are identified. The guidance is based upon a systematic review of the scientific literature, survey of the international epilepsy research community, consultation with veterinarians and animal care and welfare officers, and the expert opinion and practical experience of the members of a Working Group convened by the United Kingdom's National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs)

Quantitative Correlation at the Molecular Level of Tumor Response to Docetaxel by Multimodal Diffusion-Weighted Magnetic Resonance Imaging and [F-18]FDG/[F-18]FLT Positron Emission Tomography

We aimed to quantitatively characterize the treatment effects of docetaxel in the HCT116 xenograft mouse model, applying diffusion-weighted magnetic resonance imaging (MRI) and positron emission tomography (PET) using 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) and 3′-deoxy-3′-[ 18 F]-fluorothymidine ([ 18 F]FLT). Mice were imaged at four time points over 8 days. Docetaxel (15 mg/kg) was administered after a baseline scan. Voxel-wise scatterplots of PET and apparent diffusion coefficient (ADC) data of tumor volumes were evaluated with a threshold cluster analysis and compared to histology (GLUT1, GLUT3, Ki67, activated caspase 3a). Compared to the extensive tumor growth observed in the vehicle-treated group (from 0.32 ± 0.21 cm 3 to 0.69 ± 0.40 cm 3 ), the administration of docetaxel led to tumor growth stasis (from 0.32 ± 0.20 cm 3 to 0.45 ± 0.23 cm 3 ). The [ 18 F]FDG/ADC cluster analysis and the evaluation of peak histogram values revealed a significant treatment effect matching histology as opposed to [ 18 F]FLT/ADC. [ 18 F]FLT uptake and the Ki67 index were not in good agreement. Our voxel-based cluster analysis uncovered treatment effects not seen in the separate inspection of PET and MRI data and may be used as an independent analysis tool. [ 18 F]FLT/ADC cluster analysis could still point out the treatment effect; however, [ 18 F]FDG/ADC reflected the histology findings in higher agreement