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 common rodent models of middle cerebral artery occlusion, while sustaining or improving the scientific outcomes. The recommendations cover basic requirements pre-surgery, selecting the most appropriate anaesthetic and analgesic regimen, as well as intraoperative and post-operative care. The aim is to provide support for researchers and animal care staff to refine their procedures and practices, and implement small incremental changes to improve the welfare of the animals used and to answer the scientific question under investigation. All recommendations are recapitulated in a summary poster (see supplementary information).

Functional recovery after an experimental stroke can be assessed by multiple behavioral tests, however, there is no consensus about which test to use in long-term stroke recovery studies or whether the tests are affected by stroke surgery, post-operative care or behavioral compensation due to repeated testing. This review describes the tests most commonly used to assess motor and sensorimotor function, cognition and mood in stroke animals. Although it is difficult to predict the direction of future research, it may be possible to prevent false-positive results by selecting an appropriate task or a battery of tasks. It is also expected that the upcoming stroke recovery recommendations and the improved dialogue between academy, industry and healthcare professionals will further promote translational success.

Background Studies indicate there is a need to improve the delivery of unexpected news via obstetric ultrasound, but there have been few advances in this area. One factor preventing improvement has been a lack of consensus regarding the appropriate phrases and behaviours which sonographers and ultrasound practitioners should use in these situations. Aims To develop consensus guidelines for unexpected news delivery in Early Pregnancy Unit and Fetal Anomaly Screening Programme NHS settings. Methods A workshop was conducted to identify priorities and reach consensus on areas of contention. Contributors included interdisciplinary healthcare professionals, policy experts, representatives from third-sector organisations, lay experts and academic researchers ( n = 28). Written and verbal feedback was used to draft initial guidance which was then circulated amongst the wider writing group ( n = 39). Revisions were undertaken until consensus was reached. Results Consensus guidelines were developed outlining the behaviours and phrases which should be used during scans where unexpected findings are identified. Specific recommendations included that: honest and clear communication should be prioritised, even with uncertain findings; technical terms should be used, but these should be written down together with their lay interpretations; unless expectant parents use other terminology (e.g. ‘foetus’), the term ‘baby’ should be used as a default, even in early pregnancy; at the initial news disclosure, communication should focus on information provision. Expectant parents should not be asked to make decisions during the scan. Conclusions These recommendations can be used to develop and improve news delivery interventions in obstetric ultrasound settings. The full guidelines can be accessed online as supplemental material and at https://doi.org/10.5518/100/24 .

In order fully to utilize animal models of disease states, to test experimental therapeutics, and to understand the underlying pathophysiology of neurodegenerative disease, behavioral characterization of the model is essential. Deterioration of normal motor function within a disease state signals the progression of an underlying pathological process, and identifies disease-sensitive time points according to which the onset of therapeutic trials may be scheduled. Deterioration in the performance of motor tasks may also indicate the point when motor deficits begin to compromise our ability to measure other deficits within cognitive and behavioral domains. In acute therapeutic trials, the separation of motor from cognitive or behavioral function may be crucial in determining the functional specificity of the drug effect. If we are to accurately measure motor performance in disease progression or during drug trials, tests of motor function that have been highly optimized with respect to sensitivity must be applied. Since motor coordination and balance are essential to normal motor function, tests that probe these facets are ideal for the purpose. In this chapter, we describe in detail three test protocols that principally measure motor coordination (the rotarod and footprint tests) and balance (the elevated bridge test) in mice. Curr. Protoc. Mouse Biol. 2:37-53 © 2012 by John Wiley & Sons, Inc.

In order to test therapeutics, functional assessments are required. In pre-clinical stroke research, there is little consensus regarding the most appropriate behavioural tasks to assess deficits, especially when testing over extended times in milder models with short occlusion times and small lesion volumes. In this study, we comprehensively assessed 16 different behavioural tests, with the aim of identifying those that show robust, reliable and stable deficits for up to two months. These tasks are regularly used in stroke research, as well as being useful for examining striatal dysfunction in models of Huntington’s and Parkinson’s disease. Two cohorts of male Wistar rats underwent the intraluminal filament model of middle cerebral artery occlusion (30 min) and were imaged 24 h later. This resulted in primarily subcortical infarcts, with a small amount of cortical damage. Animals were tested, along with sham and naïve groups at 24 h, seven days, and one and two months. Following behavioural testing, brains were processed and striatal neuronal counts were performed alongside measurements of total brain and white matter atrophy. The staircase, adjusting steps, rotarod and apomorphine-induced rotations were the most reliable for assessing long-term deficits in the 30 min transient middle cerebral artery occlusion model of stroke.

The intraluminal filament procedure is the most common model of middle cerebral artery occlusion (MCAO). However, consequences of subtle variations in surgical technique on behavioral outcome measures have not been sufficiently explored, which is the aim of this study. Rats randomly received one of three types of transient MCAO (60 min) surgeries. The first transected the external carotid artery (ECA) for filament insertion. The other two inserted the filament in the carotid artery (CA), and after reperfusion, the CA was either ligated or blood flow restored. All animals, including shams and naïve controls, were monitored with behavioral tests for 90 days. Lesion size and NeuN + cells in the striatum were comparable among MCAO groups. However, rats with ECA transection were consistently lighter than rats with permanent CA ligation, which were lighter than rats with CA reperfusion. Furthermore, rats with ECA transection exhibited the poorest lick efficiency and the greatest impairments in sensorimotor tasks. This study is the first to systematically evaluate the role of ECA transection on functional and morbidity outcomes. Behavioral impairments attributable to the surgical procedure were observed. This confounds studies and is an important issue that needs to be considered when using the intraluminal filament model.

, +44 (0)161 2476210 *Title page-incl. type of article and authors name and affiliation Click here to download Title page-incl. type of article and authors name and affiliation: TitlePage.docx Highlights 1. Mice move their whiskers during tactile exploration. 2. We measure whisker movements and locomotion in 9 mouse strains. 3. Genotype, background strain, sex and source breeder affected whisker movements. 4. 8 of the 9 models showed differences in whisker movements, compared to controls. 5. We recommend a standardized protocol to measure whisker movements. *Highlights (for review) Recommendations for measuring whisker movements and locomotion in mice with sensory, motor and cognitive deficits.

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