GSK249320, A Monoclonal Antibody Against the Axon Outgrowth Inhibition Molecule Myelin-Associated Glycoprotein, Improves Outcome of Rodents with Experimental Stroke

Myelin-associated glycoprotein (MAG) is an inhibitor of axon growth. MAG levels increase after stroke. GSK249320 is a monoclonal antibody that neutralizes MAG-mediated inhibition and so may promote axon outgrowth and improve post-stroke outcomes. The current study tested the hypothesis that GSK249320 initiated 24 hours or 7 days after experimental stroke improves behavioural outcomes. Rats with right middle cerebral artery occlusion for 90 minutes were randomized to receive 6 weeks of intravenous (a) GSK249320 starting 24 hours post-stroke, (b) GSK249320 starting 7 days post-stroke, or (c) vehicle. Behavioral testing was performed over 7 weeks. Serial MRI demonstrated no differences in infarct volume across groups. Animals treated with GSK249320 24 hours post-stroke showed larger increases in Neuroscore (time X group, p = 0.0008) and staircase test (main effect of group, p = 0.0214) as compared to controls, but animals treated 7 days post-stroke showed no significant behavioral benefit. No significant results were found for the sticky tape or cylinder tests. A separate set of animals with experimental stroke received a single intravenous dose of GSK249320 or vehicle at 1 hour, 24 hours, 48 hours or 1 week post-stroke, and immunohistochemistry methods were used to measure GSK249320 distribution; GSK249320 was found in the ipsilesional hemisphere only, the extent of which increased with later times of injection. These data suggest that intravenous GSK249320 penetrates the lesion site and is associated with a small effect on functional outcomes when initiated 24 hours post-stroke and so support the translational potential of this monoclonal antibody as a restorative therapy for patients with stroke

Researching Management Practices:Understanding, Explaining and Improving the Practice of Management

This Workshop addresses theoretical and practitioner challenges in studying management practice. Many organization, strategy and management researchers have commented on the value of the practice-based approach which, drawing on movements in social sciences more generally, has been referred to as 'the practice turn' (Whittington, 2006; Schatzki, Knorr-Cetina, & von Savigny, 2001). While practice is often conceived as bundles of activities, there are significant differences in the conceptions of activities and their connections to one another. Practices are the context of action and are themselves constituted through meaningful action. Thus the study of practices incorporates understanding activities, experiences, presentation (and re-presentation), skills, learning and the materiality of action. However, a rich theoretical background and diverse contributions create conflicting advice for managers and researchers alike. The purpose of this workshop is not to reduce this rich complexity but to enable those in the field to explore the different positions adopted and to discuss where productive dialogues and debates between those positions might be fostered. The workshop is designed to facilitate discussion and mapping activities of the multiple theoretical and practitioner implications. We set out to explore the many approaches associated with different traditions of practice-based research. The workshop will be of interest to those concerned with theory building in practice-based research; the theory-practice interface; and faculty and doctoral candidates seeking research inspiration. The overarching aim is to stimulate dialogue between fields where there is an interest in practice

A method for removing global effects in small-animal functional MRI

Global effects in functional MRI are temporal modulations in signal intensity resulting from various scanner and subject phenomena. These effects contribute to the overall variance, reducing the effect size associated with an experimental paradigm. Statistical estimations that include an approximation for concurrent global effects will reduce the residual error within the model and so improve statistical power of the study. Conventionally, estimates of global effects are derived from mean intracerebral signal intensities, but these may be prone to contributions from localised experimentally evoked signal changes. In such cases, inaccurate estimates of global effects may result in erroneous inferences of neural modulations based on statistical artefact. A novel, computationally simple, method of estimating global effects is proposed using muscle tissue acquired within the same acquisition volume. Quantitative improvements in sensitivity are reported for a somatosensory stimulation paradigm using global muscle signal intensities as a covariate of no-interest. The method is independent of local neurogenic signal changes and, under particular experimental conditions, may be more representative of true global effects. The utility of this strategy to applications in small-animal functional MRI that evoke systemic physiological changes as a result of the experimental manipulation is critically discussed

Book Reviews

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GSK249320, A Monoclonal Antibody Against the Axon Outgrowth Inhibition Molecule Myelin-Associated Glycoprotein, Improves Outcome of Rodents with Experimental Stroke

Abstract Myelin-associated glycoprotein (MAG) is an inhibitor of axon growth. MAG levels increase after stroke. GSK249320 is a monoclonal antibody that neutralizes MAG-mediated inhibition and so may promote axon outgrowth and improve post-stroke outcomes. The current study tested the hypothesis that GSK249320 initiated 24 hours or 7 days after experimental stroke improves behavioural outcomes. Rats with right middle cerebral artery occlusion for 90 minutes were randomized to receive 6 weeks of intravenous (a) GSK249320 starting 24 hours post-stroke, (b) GSK249320 starting 7 days post-stroke, or (c) vehicle. Behavioral testing was performed over 7 weeks. Serial MRI demonstrated no differences in infarct volume across groups. Animals treated with GSK249320 24 hours post-stroke showed larger increases in Neuroscore (time X group, p = 0.0008) and staircase test (main effect of group, p = 0.0214) as compared to controls, but animals treated 7 days post-stroke showed no significant behavioral benefit. No significant results were found for the sticky tape or cylinder tests. A separate set of animals with experimental stroke received a single intravenous dose of GSK249320 or vehicle at 1 hour, 24 hours, 48 hours or 1 week poststroke, and immunohistochemistry methods were used to measure GSK249320 distribution; GSK249320 was found in the ipsilesional hemisphere only, the extent of which increased with later times of injection. These data suggest that intravenous GSK249320 penetrates the lesion site and is associated with a small effect on functional outcomes when initiated 24 hours post-stroke and so support the translational potential of this monoclonal antibody as a restorative therapy for patients with stroke