Restorative neuroscience: concepts and perspectives

There is increasing interest in the search for therapeutic options for diseases and injuries of the central nervous system (CNS), for which currently no effective treatment strategies are available. Replacement of damaged cells and restoration of function can be accomplished by transplantation of cells derived from different sources, such as human foetal tissue, genetically modified cell lines, embryonic or somatic stem cells. Preclinical and clinical trials have shown promising results in neurodegenerative disorders, like Parkinson's and Huntington's disease, but also ischaemic stroke, intracerebral haemorrhage, demyelinating disorders, epilepsy and traumatic lesions of the brain and spinal cord. Other studies have focused on finding new ways to activate and direct endogenous repair mechanisms in the CNS, eg, by exposure to specific neuronal growth factors or by inactivating inhibitory molecules. Neuroprotective drugs may offer an additional tool for improving neuronal survival in acute or chronic CNS diseases. Importantly however, a number of scientific issues need to be addressed in order to permit the introduction of these experimental techniques in the wider clinical setting.

Ragu: a free tool for the analysis of EEG and MEG event-related scalp field data using global randomization statistics

We present a program (Ragu; Randomization Graphical User interface) for statistical analyses of multichannel event-related EEG and MEG experiments. Based on measures of scalp field differences including all sensors, and using powerful, assumption-free randomization statistics, the program yields robust, physiologically meaningful conclusions based on the entire, untransformed, and unbiased set of measurements. Ragu accommodates up to two within-subject factors and one between-subject factor with multiple levels each. Significance is computed as function of time and can be controlled for type II errors with overall analyses. Results are displayed in an intuitive visual interface that allows further exploration of the findings. A sample analysis of an ERP experiment illustrates the different possibilities offered by Ragu. The aim of Ragu is to maximize statistical power while minimizing the need for a-priori choices of models and parameters (like inverse models or sensors of interest) that interact with and bias statistics.

Flow disturbances in stent-related coronary evaginations: a computational fluid-dynamic simulation study

Aims: Angiographic ectasias and aneurysms in stented segments have been associated with late stent thrombosis. Using optical coherence tomography (OCT), some stented segments show coronary evaginations reminiscent of ectasias. The purpose of this study was to explore, using computational fluid-dynamic (CFD) simulations, whether OCT-detected coronary evaginations can induce local changes in blood flow. Methods and results: OCT-detected evaginations are defined as outward bulges in the luminal vessel contour between struts, with the depth of the bulge exceeding the actual strut thickness. Evaginations can be characterised cross ectionally by depth and along the stented segment by total length. Assuming an ellipsoid shape, we modelled 3-D evaginations with different sizes by varying the depth from 0.2-1.0 mm, and the length from 1-9 mm. For the flow simulation we used average flow velocity data from non-diseased coronary arteries. The change in flow with varying evagination sizes was assessed using a particle tracing test where the particle transit time within the segment with evagination was compared with that of a control vessel. The presence of the evagination caused a delayed particle transit time which increased with the evagination size. The change in flow consisted locally of recirculation within the evagination, as well as flow deceleration due to a larger lumen - seen as a deflection of flow towards the evagination. Conclusions: CFD simulation of 3-D evaginations and blood flow suggests that evaginations affect flow locally, with a flow disturbance that increases with increasing evagination size.

Computational tools to investigate genetic cardiac channelopathies

The aim of this perspective article is to share with the community of ion channel scientists our thoughts and expectations regarding the increasing role that computational tools will play in the future of our field. The opinions and comments detailed here are the result of a 3-day long international exploratory workshop that took place in October 2013 and that was supported by the Swiss National Science Foundation.