Development of a novel model of optic neuritis to assess neuroprotective and repair strategies in multiple sclerosis

PhDMultiple sclerosis (MS) is a putative autoimmune disease of the central nervous system (CNS), which often affects the optic nerve pathway. Optic neuritis (ON) is a clinical feature of MS that can cause loss of vision due to conduction block and demyelination. Visual function may not recover due to axonal loss in the optic nerve and subsequent loss of retinal ganglion cells (RGC) in the retina. The visual system is the most accessible and best studied part of the CNS and provides an ideal target to monitor the efficacy of strategies aimed at neuroprotection and repair. A C57BL/6 mouse expressing a T cell receptor (TCR) transgene specific for 35-55 residues of myelin oligodendrocyte glycoprotein (MOG), which develops ON spontaneously (approximately 5%) was characterised and an immunising protocol developed with a combination of immune adjuvants (Pertussis toxin, MOG-specific Z12 monoclonal antibody) to give a high incidence of disease. ON is associated with extensive axonal loss in the optic nerve and RGC loss in the retina. These animals were crossed with C57BL/6.Thy1 CFP mice, which express cyan fluorescent protein (CFP) under control of a Thy1 promoter that limits expression of CFP to the RGC in the eye. The resultant MOGTCRxThy1CFP mice develop ON leading to neuronal loss that can be monitored longitudinally in “real-time” in the living animal using techniques that correlate with studies undertaken in humans (visually evoked potentials, scanning laser ophthalmoscopy and optical coherence tomography). These techniques were used in the MOGTCRxThy1CFP to study neuroprotective and repair therapies for their potential in human trials. This novel model of optic neuritis will be invaluable for the study of neuroprotective and repair strategies in autoimmune diseases and offers a refinement of previous models of MS, such as “classical” EAE

Two Years Later: Journals Are Not Yet Enforcing the ARRIVE Guidelines on Reporting Standards for Pre-Clinical Animal Studies

There is growing concern that poor experimental design and lack of transparent reporting contribute to the frequent failure of pre-clinical animal studies to translate into treatments for human disease. In 2010, the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines were introduced to help improve reporting standards. They were published in PLOS Biology and endorsed by funding agencies and publishers and their journals, including PLOS, Nature research journals, and other top-tier journals. Yet our analysis of papers published in PLOS and Nature journals indicates that there has been very little improvement in reporting standards since then. This suggests that authors, referees, and editors generally are ignoring guidelines, and the editorial endorsement is yet to be effectively implemented

Research-Informed Teaching Toolkit

Research-informed teaching is a term used to describe the different ways in which students are exposed to research content and activities during their time at university. Depending on your discipline this could also be called practice-informed teaching. A four-year body of research involving over 600 students from across Sheffield Hallam University has been used to draw together the following five key Curriculum Design Principles to embed research and practice into teaching:1) Embed research and practice skills at the course level and develop them through the course. Moving students from consumers of research and best practice to creators of research and best practice. 2) Academic research and practice can form the basis of taught content and be used as direct examples of applied knowledge. 3) Accessing research literature is a high-level skill and requires scaffolding. 4) Research and practice skills should be taught in context and task linked. 5) Research undertaken by the students should be co-created, with students involved in the design process. Students and University staff from Sport, Nursing, Midwifery, Biosciences and Chemistry were involved in the creation of this toolkit. This toolkit is most relevant for those looking to embed research-informed teaching in their practice. The toolkit includes an introduction to research-informed teaching, how students perceive research, the barriers and enablers for staff and students to engage with research-informed teaching, skills students develop and ideas for the integration of research-informed teaching

Neuroprotection in a Novel Mouse Model of Multiple Sclerosis

The authors acknowledge the support of the Barts and the London Charity, the Multiple Sclerosis Society of Great Britain and Northern Ireland, the National Multiple Sclerosis Society, USA, notably the National Centre for the Replacement, Refinement & Reduction of Animals in Research, and the Wellcome Trust (grant no. 092539 to ZA). The siRNA was provided by Quark Pharmaceuticals. The funders and Quark Pharmaceuticals had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Imidazol-1-ylethylindazole Voltage-Gated Sodium Channel Ligands Are Neuroprotective during Optic Neuritis in a Mouse Model of Multiple Sclerosis

[Image: see text] A series of imidazol-1-ylethylindazole sodium channel ligands were developed and optimized for sodium channel inhibition and in vitro neuroprotective activity. The molecules exhibited displacement of a radiolabeled sodium channel ligand and selectivity for blockade of the inactivated state of cloned neuronal Na(v) channels. Metabolically stable analogue 6 was able to protect retinal ganglion cells during optic neuritis in a mouse model of multiple sclerosis

Reporting animal research:Explanation and elaboration for the ARRIVE guidelines 2.0

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 help authors and journals identify the minimum information necessary to report in publications describing in vivo experiments. Despite widespread endorsement by the scientific community, the impact of ARRIVE on the transparency of reporting in animal research publications has been limited. We have revised the ARRIVE guidelines to update them and facilitate their use in practice. The revised guidelines are published alongside this paper. This explanation and elaboration document was developed as part of the revision. It provides further information about each of the 21 items in ARRIVE 2.0, including the rationale and supporting evidence for their inclusion in the guidelines, elaboration of details to report, and examples of good reporting from the published literature. This document also covers advice and best practice in the design and conduct of animal studies to support researchers in improving standards from the start of the experimental design process through to publication

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)