Neuroplasticity can be defined as the ability of the nervous system to respond to intrinsic or extrinsic stimuli by reorganizing its structure, function and connections. Major advances in the understanding of neuroplasticity have to date yielded few established interventions. To advance the translation of neuroplasticity research towards clinical applications, the National Institutes of Health Blueprint for Neuroscience Research sponsored a workshop in 2009. Basic and clinical researchers in disciplines from central nervous system injury/stroke, mental/addictive disorders, paediatric/developmental disorders and neurodegeneration/ageing identified cardinal examples of neuroplasticity, underlying mechanisms, therapeutic implications and common denominators. Promising therapies that may enhance training-induced cognitive and motor learning, such as brain stimulation and neuropharmacological interventions, were identified, along with questions of how best to use this body of information to reduce human disability. Improved understanding of adaptive mechanisms at every level, from molecules to synapses, to networks, to behaviour, can be gained from iterative collaborations between basic and clinical researchers. Lessons can be gleaned from studying fields related to plasticity, such as development, critical periods, learning and response to disease. Improved means of assessing neuroplasticity in humans, including biomarkers for predicting and monitoring treatment response, are needed. Neuroplasticity occurs with many variations, in many forms, and in many contexts. However, common themes in plasticity that emerge across diverse central nervous system conditions include experience dependence, time sensitivity and the importance of motivation and attention. Integration of information across disciplines should enhance opportunities for the translation of neuroplasticity and circuit retraining research into effective clinical therapies.

Abstract. Extracts of the electric organ of Torpedo californica contain a proteinaceous factor that causes the formation of patches on cultured myotubes at which acetylcholine receptors (AChR), acetylcholinesterase (ACHE), and butyrylcholinesterase (BuChE) are concentrated. Results of previous experiments indicate that this factor is similar to the molecules in the synaptic basal lamina that direct the aggregation of AChR and AChE at regenerating neuromuscular junctions in vivo. We have purified the active components in the extracts 9,000-fold. mAbs against four different epitopes on the AChR/AChE/BuChE-aggregating molecules each immunoprecipitated four polypeptides from electric organ extracts, with molecular masses of 150, 135, 95, and 70 kD. Gel filtration chromatography of electric organ extracts revealed tw~ peaks of AChR/ AChE/BuChE-aggregating activity; one comigrated with the 150-kD polypeptide, the other with the 95-kD polypeptide. The 135-and 70-kD polypeptides did not cause AChR/AChE/BuChE aggregation. Based on these molecular characteristics and on the pattern of staining seen in sections of muscle labeled with the mAbs, we conclude that the electric organ-aggregating factor is distinct from previously identified molecules, and we have named it "agrin:

The synaptic portion of a muscle fiber's basal lamina sheath has molecules tightly bound to it that cause aggregation of acetylcholine receptors (AChRs) on regenerating myofibers . Since basal lamina and other extracellular matrix constituents are insoluble in isotonic saline and detergent solutions, insoluble detergent-extracted fractions of tissues receiving cholinergic input may provide an enriched source of the AChR-aggregating molecules for detailed characterization . Here we demonstrate that such an insoluble fraction from Torpedo electric organ, a tissue with a high concentration of cholinergic synapses, causes AChRs on cultured chick muscle cells to aggregate . We have partially characterized the insoluble fraction, examined the response of muscle cells to it, and devised ways of extracting the active components with a view toward purifying them and learning whether they are similar to those in the basal lamina at the neuromuscular junction.The insoluble fraction from the electric organ was rich in extracellular matrix constituents ; it contained structures resembling basal lamina sheaths and had a high density of collagen fibrils . It caused a 3-to 20-fold increase in the number of AChR clusters on cultured myotubes without significantly affecting the number or size of the myotubes . The increase was first seen 2-4 h after the fraction was added to cultures and it was maximal by 24 h. The AChRaggregating effect was dose dependent and was due, at least in part, to lateral migration of AChRs present in the muscle cell plasma membrane at the time the fraction was applied . Activity was destroyed by heat and by trypsin . The active component(s) was extracted from the insoluble fraction with high ionic strength or pH 5 .5 buffers . The extracts increased the number of AChR clusters on cultured myotubes without affecting the number or degradation rate of surface AChRs. Antiserum against the solubilized material blocked its effect on AChR distribution and bound to the active component .Insoluble fractions of Torpedo muscle and liver did not cause AChR aggregation on cultured myotubes. However a low level of activity was detected in pH 5 .5 extracts from the muscle fraction . The active component(s) in the muscle extract was immunoprecipitated by the antiserum against the material extracted from the electric organ insoluble fraction . This antiserum also bound to extracellular matrix in frog muscles, including the myofiber basal lamina sheath . Thus the insoluble fraction of Torpedo electric organ is rich in AChR-aggregating molecules that are also found in muscle and has components antigenically similar to those in myofiber basal lamina .Each muscle fiber in skeletal muscles is ensheathed by basal lamina, a component ofextracellular matrix that lies adjacent to the myofiber plasma membrane. The portion of the basal THE JOURNAL OF CELL BIOLOGY -VOLUME 99 AUGUST 1984 615-627 C The Rockefeller University Press -0021-9525/84/08/0615/13 $1 .00 lamina in the synaptic cleft at the neuromuscular junction is h...

The health care delivery system in the United States is challenged to meet the needs of a growing population of cancer survivors. A pressing need is to optimize overall function and reduce disability in these individuals. Functional impairments and disability affect most patients during and after disease treatment. Rehabilitation health care providers can diagnose and treat patients' physical, psychological, and cognitive impairments in an effort to maintain or restore function, reduce symptom burden, maximize independence and improve quality of life in this medically complex population. However, few care delivery models integrate comprehensive cancer rehabilitation services into the oncology care continuum. The Rehabilitation Medicine Department of the Clinical Center at the National Institutes of Health with support from the National Cancer Institute and the National Center for Medical Rehabilitation Research convened a subject matter expert group to review current literature and practice patterns, identify opportunities and gaps regarding cancer rehabilitation and its support of oncology care, and make recommendations for future efforts that promote quality cancer rehabilitation care. The recommendations suggest stronger efforts toward integrating cancer rehabilitation care models into oncology care from the point of diagnosis, incorporating evidence-based rehabilitation clinical assessment tools, and including rehabilitation professionals in shared decision-making in order to provide comprehensive cancer care and maximize the functional capabilities of cancer

Background and Purpose The aim of the Synergium was to devise and prioritize new ways of accelerating progress in reducing the risks, effects, and consequences of stroke. Methods Preliminary work was performed by 7 working groups of stroke leaders followed by a synergium (a forum for working synergistically together) with approximately 100 additional participants. The resulting draft document had further input from contributors outside the synergium. Results Recommendations of the Synergium are: Basic Science, Drug Development and Technology: There is a need to develop: (1) New systems of working together to break down the prevalent “silo” mentality; (2) New models of vertically integrated basic, clinical, and epidemiological disciplines; and (3) Efficient methods of identifying other relevant areas of science. Stroke Prevention: (1) Establish a global chronic disease prevention initiative with stroke as a major focus. (2) Recognize not only abrupt clinical stroke, but subtle subclinical stroke, the commonest type of cerebrovascular disease, leading to impairments of executive function. (3) Develop, implement and evaluate a population approach for stroke prevention. (4) Develop public health communication strategies using traditional and novel (eg, social media/marketing) techniques. Acute Stroke Management: Continue the establishment of stroke centers, stroke units, regional systems of emergency stroke care and telestroke networks. Brain Recovery and Rehabilitation: (1) Translate best neuroscience, including animal and human studies, into poststroke recovery research and clinical care. (2) Standardize poststroke rehabilitation based on best evidence. (3) Develop consensus on, then implementation of, standardized clinical and surrogate assessments. (4) Carry out rigorous clinical research to advance stroke recovery. Into the 21st Century: Web, Technology and Communications: (1) Work toward global unrestricted access to stroke-related information. (2) Build centralized electronic archives and registries. Foster Cooperation Among Stakeholders (large stroke organizations, nongovernmental organizations, governments, patient organizations and industry) to enhance stroke care. Educate and energize professionals, patients, the public and policy makers by using a “Brain Health” concept that enables promotion of preventive measures. Conclusions To accelerate progress in stroke, we must reach beyond the current status scientifically, conceptually, and pragmatically. Advances can be made not only by doing, but ceasing to do. Significant savings in time, money, and effort could result from discontinuing practices driven by unsubstantiated opinion, unproven approaches, and financial gain. Systematic integration of knowledge into programs coupled with careful evaluation can speed the pace of progress.

Cancer rehabilitation research has accelerated as great attention has focused on improving survivorship care. Recent expert consensus has attempted to prioritize research needs and suggests greater focus on studying physical functioning of survivors. However, no analysis of the publication landscape has substantiated these proposed needs. This manuscript provides an analysis of PubMed indexed articles related to cancer rehabilitation published between 1992 and 2017. A total of 22 171 publications were analyzed using machine learning and text analysis to assess publication metrics, topic areas of emphasis, and their interrelationships through topic similarity networks. Publications have increased at a rate of 136 articles per year. Approximately 10% of publications were funded by the National Institutes of Health institutes and centers, with the National Cancer Institute being the most prominent funder. The greatest volume and rate of publication increase were in the topics of Cognitive and Behavioral Therapies and Psychological Interventions, followed by Depression and Exercise Therapy. Four research topic similarity networks were identified and provide insight on areas of robust publication and notable deficits. Findings suggest that publication emphasis has strongly supported cognitive, behavioral, and psychological therapies; however, studies of functional morbidity and physical rehabilitation research are lacking. Three areas of publication deficits are noted: research on populations outside of breast, prostate, and lung cancers; methods for integrating physical rehabilitation services with cancer care, specifically regarding functional screening and assessment; and physical rehabilitation interventions. These deficits align with the needs identified by expert consensus and support the supposition that future research should emphasize a focus on physical rehabilitation.

The basal lamina in the synaptic cleft of the vertebrate skeletal neuromuscular junction contains molecules that direct the formation of synaptic specializations in regenerating axons and muscle fibres. We have undertaken a series of experiments aimed at identifying and characterizing the molecules responsible for the formation of one of these specializations, the aggregates of acetylcholine receptors (AChRs) in the muscle fibre plasma membrane. We began by preparing an insoluble, basal lamina-containing fraction from Torpedo californica electric organ, a tissue which has a far higher concentration of cholinergic synapses than muscle, and showing that this fraction caused AChRs on cultured chick myotubes to aggregate. A critical step is learning whether or not the electric organ factor is similar to the receptor-aggregating molecule in the basal lamina at the neuromuscular junction. The importance of this problem is emphasized by reports that clearly non-physiological agents, such as positively charged latex beads, can cause AChR aggregation on cultured muscle cells. We have already shown that Torpedo muscle contains an AChR-aggregating factor similar to that of electric organ, although in much lower amounts. Here we demonstrate, using monoclonal antibodies, that the AChR-aggregating factor in our extracts of electric organ is, in fact, antigenically related to molecules concentrated in the synaptic cleft at the neuromuscular junction.

Basal lamina-rich extracts of Torpedo californica electric organ contain a factor that causes acetylcholine receptors (AChRs) on cultured myotubes to aggregate into patches. Our previous studies have indicated that the active component of these extracts is similar to the molecules in the basal lamina which direct the aggregation of AChRs in the muscle fibre plasma membrane at regenerating neuromuscular junctions in vivo. Because it can be obtained in large amounts and assayed in controlled conditions in cell culture, the AChR-aggregating factor from electric organ may be especially useful for examining in detail how the postsynaptic apparatus of regenerating muscle is assembled. Here we demonstrate that the electric organ factor causes not only the formation of AChR aggregates on cultured myotubes, but also the formation of patches of acetylcholinesterase (AChE). This finding, together with the observation that basal lamina directs the formation of both AChR and AChE aggregates at regenerating neuromuscular junctions in vivo, leads us to hypothesize that a single component of the synaptic basal lamina causes the formation of both these synaptic specializations on regenerating myofibres.