Background and Purpose-Skilled reaching movements are an important aspect of human motor behavior but are impaired after motor system stroke. The purpose of this study was to document skilled movements in mice before and after a focal motor cortex stroke for the purpose of developing a mouse model of human stroke. Methods-Male C57/BL6 mice were trained to reach with a forelimb for food pellets and then given a motor cortex stroke, induced by pial stripping, contralateral to their preferred reaching limb. Reaching success and the movements used in reaching were analyzed by frame-by-frame inspection of presurgical and postsurgical video records. Results-Reaching success was severely impaired after the stroke. Improvement in success over 2 postsurgical weeks was moderate. Analysis of 10 movement components comprising reaches pre-and postsurgically indicated that most of the rotatory movements of the limb used for aiming, advancing, pronating, and supinating the paw were impaired. When successful reaches did occur, body movements that compensated for the impairments in limb rotatory movements aided them. Conclusions-The results indicate that skilled reaching in the mouse is impaired by focal motor cortex stroke and they suggest that the mouse, and the skilled reaching task, provides an excellent model for studying impairments, compensation, and recovery after motor system stroke.

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One of the hallmarks of stroke pathophysiology is the widespread death of many different types of brain cells. As our understanding of the complex disease that is stroke has grown, it is now generally accepted that various different mechanisms can result in cell damage and eventual death. A plethora of techniques is available to identify various pathological features of cell death in stroke; each has its own drawbacks and pitfalls, and most are unable to distinguish between different types of cell death, which partially explains the widespread misuse of many terms. The purpose of this review is to summarize the standard histopathological and immunohistochemical techniques used to identify various pathological features of stroke. We then discuss how these methods should be properly interpreted on the basis of what they are showing, as well as advantages and disadvantages that require consideration. As there is much interest in the visualization of stroke using noninvasive imaging strategies, we also specifically discuss how these techniques can be interpreted within the context of cell death.

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).

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Despite promising results in preclinical stroke research, translation of experimental data into clinical therapy has been difficult. One reason is the heterogeneity of the disease with outcomes ranging from complete recovery to continued decline. A successful treatment in one situation may be ineffective, or even harmful, in another. To overcome this, treatment must be tailored according to the individual based on identification of the risk of damage and estimation of potential recovery. Neuroimaging, particularly magnetic resonance imaging (MRI), could be the tool for a rapid comprehensive assessment in acute stroke with the potential to guide treatment decisions for a better clinical outcome. This review describes current MRI techniques used to characterize stroke in a preclinical research setting, as well as in the clinic. Furthermore, we will discuss current developments and the future potential of neuroimaging for stroke outcome prediction.

Lesion volume measurements with magnetic resonance imaging are widely used to assess outcome in rodent models of stroke. In this study, we improved a mathematical framework to correct lesion size for edema which is based on manual delineation of the lesion and hemispheres. Furthermore, a novel MATLAB toolbox to register mouse brain MR images to the Allen brain atlas is presented. Its capability to calculate edema-corrected lesion size was compared to the manual approach. Automated image registration performed equally well in in a mouse middle cerebral artery occlusion model (Pearson r ¼ 0.976, p ¼ 2.265e-11). Information encapsulated in the registration was used to generate maps of edema induced tissue volume changes. These showed discrepancies to simplified tissue models underlying the manual approach. The presented techniques provide biologically more meaningful, voxel-wise biomarkers of vasogenic edema after stroke.

Cell tracking by in vivo magnetic resonance imaging (MRI) requires strategies of labelling the cells with MRI contrast agents. The principal routes to achieve efficient cell labelling for neurological applications are discussed with methodological advantages and caveats. Beyond temporo-spatial localization of labelled cells, the investigation of functional cell status is of great interest to allow studies of functional cell dynamics. The two major approaches to reach this goal, use of responsive contrast agents and generation of transgenic cell lines, are discussed.