1,720,973 research outputs found
Studying and modulating post-stroke neuroplasticity to improve motor recovery
Full text linkLimited restoration of motor function occurs spontaneously during a plastic time window after stroke. A deeper understanding of post-stroke plasticity is critical to devise more effective pharmacological and rehabilitative treatments.
Here, I have characterized the spontaneous evolution after a photothrombotic lesion in mice, both in terms of motor deficit and plasticity in the perilesional cortex. In generalized motor tasks such as the Gridwalk and Schallert Cylinder test, motor deficits were stable for at least 30 days after photothrombotic stroke in the Caudal Forelimb Area (CFA). The skilled reaching test, performed once a week, showed a trend for spontaneous improvement over time in the number of correct graspings. However, kinematic analysis, evaluated by means of an innovative semi-automated tool, revealed a persistent alterations in grasping movements, pointing to the development of compensatory strategies.
The perilesional cortex has been proposed as the area mediating functional recovery. I found a reorganization of the motor maps in sensorimotor cortex around to the lesion. Particularly, I observed a significant shrinkage of the forelimb area, in favour of hindlimb representation using Intracortical Microstimulation (ICMS). Moreover, neuroanatomical markers, previously characterized in the literature as “neuroplasticity brakes” (i.e. Perineuronal nets, Parvalbumin- and Somatostatin-positive cells) spontaneously decrease after stroke, suggesting an enhancement of the potential for plastic rearrangements. Altogether these results, suggest a spontaneous attempt to reopen a critical period characterized by sprouting and plasticity phenomena, that needs to be amplified and properly guided for maximizing recovery.
The GABAergic system is one of the key modulators of plasticity in the brain, and its role has been amply studied in relation to opening and closure of the “critical period” in sensory cortices during development. To test whether reductions in GABAergic signalling were causally involved in motor improvements, we treated animals during an early post-stroke period with a benzodiazepine inverse agonist, which impairs GABAA receptor function. We found that hampering GABAA signalling led to significant restoration of function in general motor tests such as the gridwalk and the pellet reaching tasks, with no significant impact on the kinematics of reaching movements. Improvements were persistent as they remained detectable about three weeks after treatment.
Using electrophysiological recordings I found an electrical imbalance between the two hemispheres. In particular, contralesional motor cortex was found to exert an enhanced transcallosal inhibition over the spared, perilesional tissue. Silencing the healthy hemisphere using cortical infusion of Botulinum Neurotoxin E, partially improved motor recovery in the gridwalk test.
We then established a rehabilitation protocol that combined intensive and highly repeatable exercise of the mouse forelimb with a robotic platform with reversible inactivation of the healthy, contralesional motor cortex. We found that such treatment promoted recovery in both Gridwalk and Schallert Cylinder tests and in end point measures during Skilled reaching test. Remarkably, the combined therapy also restores pre-lesion movement patterns during reaching movement, as evaluated by kinematic analysis. Furthermore, such rehabilitated animals showed a more plastic perilesional cortex, with an additional significant decrease in plasticity brakes
Pluripotent Stem Cells for Brain Repair: Protocols and Preclinical Applications in Cortical and Hippocampal Pathologies
Full text linkBrain injuries causing chronic sensory or motor deficit, such as stroke, are among the leading causes of disability worldwide, according to the World Health Organization; furthermore, they carry heavy social and economic burdens due to decreased quality of life and need of assistance. Given the limited effectiveness of rehabilitation, novel therapeutic strategies are required to enhance functional recovery. Since cell-based approaches have emerged as an intriguing and promising strategy to promote brain repair, many efforts have been made to study the functional integration of neurons derived from pluripotent stem cells (PSCs), or fetal neurons, after grafting into the damaged host tissue. PSCs hold great promises for their clinical applications, such as cellular replacement of damaged neural tissues with autologous neurons. They also offer the possibility to create in vitro models to assess the efficacy of drugs and therapies. Notwithstanding these potential applications, PSC-derived transplanted neurons have to match the precise sub-type, positional and functional identity of the lesioned neural tissue. Thus, the requirement of highly specific and efficient differentiation protocols of PSCs in neurons with appropriate neural identity constitutes the main challenge limiting the clinical use of stem cells in the near future. In this Review, we discuss the recent advances in the derivation of telencephalic (cortical and hippocampal) neurons from PSCs, assessing specificity and efficiency of the differentiation protocols, with particular emphasis on the genetic and molecular characterization of PSC-derived neurons. Second, we address the remaining challenges for cellular replacement therapies in cortical brain injuries, focusing on electrophysiological properties, functional integration and therapeutic effects of the transplanted neurons
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispositivo automatizzato per la riabilitazione motoria e per la valutazione della funzionalità degli arti anteriori in modelli animali
No full textPost-stroke spontaneous motor recovery in mice can be predicted from acute-phase local field potential using machine learning
Full text linkStroke remains a leading cause of long-term disability, underscoring the urgent need for effective predictors of motor recovery. Understanding the electrophysiological changes underlying spontaneous recovery could offer critical insight into recovery mechanisms and aid in predicting individual rehabilitation trajectories. In this study, we investigated the predictive power of local field potentials recorded 2 days post-stroke to forecast 1 month motor recovery in a mouse model of ischemic stroke. By employing a comprehensive machine learning approach, we identified key electrophysiological features that significantly enhanced prediction accuracy. Through nested leave-one-animal-out cross-validation, we achieved high prediction accuracy, correctly identifying motor recovery status in 15 out of 16 mice. Our findings also revealed that pre-stroke brain activity did not contribute to prediction accuracy, suggesting that post-stroke dynamics are the primary determinants of recovery. Notably, we found that features from the contralesional hemisphere were particularly influential in predicting recovery outcomes, underscoring the critical role of the non-lesioned hemisphere in motor recovery. Our data-driven methodology underscores the importance of balancing feature selection to optimize predictive performance, particularly in the context of spontaneous recovery, where insight into natural recovery processes can guide the development of targeted rehabilitation strategies. Ultimately, our findings advocate for a deeper understanding of post-stroke brain dynamics to improve clinical outcomes for stroke patients
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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