Blowing up Neural Repair for Stroke Recovery: Preclinical and Clinical Trial Considerations

The repair and recovery of the brain after stroke is a field that is emerging in its preclinical science and clinical trials. However, recent large, multicenter clinical trials have been negative, and conflicting results emerge on biological targets in preclinical studies. The coalescence of negative clinical translation and confusion in preclinical studies raises the suggestion that perhaps the field of stroke recovery faces a fate similar to stroke neuroprotection, with interesting science ultimately proving difficult to translate to the clinic. This review highlights improvements in 4 areas of the stroke neural repair field that should reorient the field toward successful clinical translation: improvements in rodent genetic models of stroke recovery, consideration of the biological target in stroke recovery, stratification in clinical trials, and the use of appropriate clinical trial end points

Evaluating regional emission estimates using the TRACE-P observations

Measurements obtained during the NASA Transport and Chemical Evolution over the Pacific (TRACE-P) experiment are used in conjunction with regional modeling analysis to evaluate emission estimates for Asia. A comparison between the modeled values and the observations is one method to evaluate emissions. Based on such analysis it is concluded that the inventory performs well for the light alkanes, CO, ethyne, SO2, and NOₓ. Furthermore, based on model skill in predicting important photochemical species such as O₃, HCHO, OH, HO₂, and HNO₃, it is found that the emissions inventories are of sufficient quality to support preliminary studies of ozone production. These are important finding in light of the fact that emission estimates for many species (such as speciated NMHCs and BC) for this region have only recently been estimated and are highly uncertain. Using a classification of the measurements built upon trajectory analysis, we compare observed species distributions and ratios of species to those modeled and to ratios estimated from the emissions inventory. It is shown that this technique can reconstruct a spatial distribution of propane/benzene that looks remarkably similar to that calculated from the emissions inventory. A major discrepancy between modeled and observed behavior is found in the Yellow Sea, where modeled values are systematically underpredicted. The integrated analysis suggests that this may be related to an underestimation of emissions from the domestic sector. The emission is further tested by comparing observed and measured species ratios in identified megacity plumes. Many of the model derived ratios (e.g., BC/CO, SOₓ/C₂H₂) fall within ∼25% of those observed and all fall outside of a factor of 2.5. (See Article file for details of the abstract.)Department of Civil and Environmental EngineeringAuthor name used in this publication: Wang, T

Agreed Definitions and a Shared Vision for New Standards in Stroke Recovery Research: The Stroke Recovery and Rehabilitation Roundtable Taskforce

The first Stroke Recovery and Rehabilitation Roundtable established a game changing set of new standards for stroke recovery research. Common language and definitions were required to develop an agreed framework spanning the four working groups: translation of basic science, biomarkers of stroke recovery, measurement in clinical trials and intervention development and reporting. This paper outlines the working definitions established by our group and an agreed vision for accelerating progress in stroke recovery research

The statistical neuroanatomy of frontal networks in the macaque

We were interested in gaining insight into the functional properties of frontal networks based upon their anatomical inputs. We took a neuroinformatics approach, carrying out maximum likelihood hierarchical cluster analysis on 25 frontal cortical areas based upon their anatomical connections, with 68 input areas representing exterosensory, chemosensory, motor, limbic, and other frontal inputs. The analysis revealed a set of statistically robust clusters. We used these clusters to divide the frontal areas into 5 groups, including ventral-lateral, ventral-medial, dorsal-medial, dorsal-lateral, and caudal-orbital groups. Each of these groups was defined by a unique set of inputs. This organization provides insight into the differential roles of each group of areas and suggests a gradient by which orbital and ventral-medial areas may be responsible for decision-making processes based on emotion and primary reinforcers, and lateral frontal areas are more involved in integrating affective and rational information into a common framework

Low-frequency cortical activity is a neuromodulatory target that tracks recovery after stroke.

Recent work has highlighted the importance of transient low-frequency oscillatory (LFO; <4 Hz) activity in the healthy primary motor cortex during skilled upper-limb tasks. These brief bouts of oscillatory activity may establish the timing or sequencing of motor actions. Here, we show that LFOs track motor recovery post-stroke and can be a physiological target for neuromodulation. In rodents, we found that reach-related LFOs, as measured in both the local field potential and the related spiking activity, were diminished after stroke and that spontaneous recovery was closely correlated with their restoration in the perilesional cortex. Sensorimotor LFOs were also diminished in a human subject with chronic disability after stroke in contrast to two non-stroke subjects who demonstrated robust LFOs. Therapeutic delivery of electrical stimulation time-locked to the expected onset of LFOs was found to significantly improve skilled reaching in stroke animals. Together, our results suggest that restoration or modulation of cortical oscillatory dynamics is important for the recovery of upper-limb function and that they may serve as a novel target for clinical neuromodulation

Intermediate-depth icequakes and harmonic tremor in an Alpine glacier (glacier d 'Argentiere,France): evidence for hydraulic fracturing

International audienceWe detected several thousand deep englacial icequakes on Glacier d’Argentiere (Mont-Blanc Massif) between 30 March and 3 May 2012. These events have been classified in eight clusters. Inside each cluster, the waveforms are similar for P-waves and S-waves, although the time delay between the P-waves and S-waves vary by up to 0.03 s, indicating an extended source area. Although these events were recorded by a single accelerometer, they were roughly located using a polarization analysis. The deepest events were located at a depth of 130 m, 60 m above the ice/bed interface. The clusters are separated in space. The largest cluster extends over about 100 m. For this cluster, the strike of the rupture plane is nearly parallel to the direction of the open crevasses, and the dip angle is 56◦. Deep icequakes occur in bursts of activity that last for a few hours and are separated by quiet periods. Many events occurred on 28-29 April 2012, during the warmest days, when snow melting was likely important. The distribution of events in time and space obeys a power law, as also observed for earthquakes, but with larger exponents.The polarity of the P-waves for all of the events is consistent with tensile faulting. Finally, between 25 April and 3 May, we observed a gliding harmonic tremor with a fun- damental resonance frequency that varied between 30 Hz and 38 Hz, with additional higher frequency harmonics. During this time we also observed shallow hybrid events with high-frequency onsets and a monochromatic coda. These events might be produced by the propagation of fractures and the subsequent flow of water into the fracture. The strongest resonance was observed just after a strong burst of deep icequakes, and during an un- usually warm period when the snow height decreased by 60 cm in one week. The res- onance frequency shows a succession of several sharp decreases and phases of progressive increases. One of the strongest negative steps of the resonance frequency on 28 April coincides with a burst of deep icequakes. These events appear to be associated with the propagation of fractures, which can explain the decrease in the resonance frequency. Finally, we observed an acceleration of glacier flow on 29 April and suggested that melt-water had reached the ice/bed interface. These observations suggest that deep icequakes are due to hydraulic fracturing, and that they can be used to track fluid flow inside glaciers

In Vivo Imaging of Stepwise Vessel Occlusion in Cerebral Photothrombosis of Mice by 19F MRI

Background $^{19}$F magnetic resonance imaging (MRI) was recently introduced as a promising technique for in vivo cell tracking. In the present study we compared $^{19}$F MRI with iron-enhanced MRI in mice with photothrombosis (PT) at 7 Tesla. PT represents a model of focal cerebral ischemia exhibiting acute vessel occlusion and delayed neuroinflammation. Methods/Principal Findings Perfluorocarbons (PFC) or superparamagnetic iron oxide particles (SPIO) were injected intravenously at different time points after photothrombotic infarction. While administration of PFC directly after PT induction led to a strong $^{19}$F signal throughout the entire lesion, two hours delayed application resulted in a rim-like $^{19}$F signal at the outer edge of the lesion. These findings closely resembled the distribution of signal loss on T2-weighted MRI seen after SPIO injection reflecting intravascular accumulation of iron particles trapped in vessel thrombi as confirmed histologically. By sequential administration of two chemically shifted PFC compounds 0 and 2 hours after illumination the different spatial distribution of the $^{19}$F markers (infarct core/rim) could be visualized in the same animal. When PFC were applied at day 6 the fluorine marker was only detected after long acquisition times ex vivo. SPIO-enhanced MRI showed slight signal loss in vivo which was much more prominent ex vivo indicative for neuroinflammation at this late lesion stage. Conclusion Our study shows that vessel occlusion can be followed in vivo by $^{19}$F and SPIO-enhanced high-field MRI while in vivo imaging of neuroinflammation remains challenging. The timing of contrast agent application was the major determinant of the underlying processes depicted by both imaging techniques. Importantly, sequential application of different PFC compounds allowed depiction of ongoing vessel occlusion from the core to the margin of the ischemic lesions in a single MRI measurement

Challenging a culture of racial equivalence

We live at a time when our understandings and conceptualizations of ‘racism’ are often highly imprecise, broad, and used to describe a wide range of racialized phenomena. In this article, I raise some important questions about how the term racism is used and understood in contemporary British society by drawing on some recent cases of alleged racism in football and politics, many of which have been played out via new media technologies. A broader understanding of racism, through the use of the term ‘racialization’, has been helpful in articulating a more nuanced and complex understanding of racial incidents, especially of people’s (often ambivalent) beliefs and behaviours. However, the growing emphasis upon ‘racialization’ has led to a conceptualization of racism which increasingly involves multiple perpetrators, victims, and practices without enough consideration of how and why particular interactions and practices constitute racism as such.The trend toward a growing culture of racial equivalence is worrying, as it denudes the idea of racism of its historical basis, severity and power.These frequent and commonplace assertions of racism in the public sphere paradoxically end up trivializing and homogenizing quite different forms of racialized interactions. I conclude that we need to retain the term ‘racism’, but we need to differentiate more clearly between ‘racism’ (as an historical and structured system of domination) from the broader notion of ‘racialization’