NeuroRx RSS feed: Current Issue. http://www.journals.elsevierhealth.com/periodicals/nurx/?rss=yesElsevier Inc.en © 2006 Published by Elsevier Inc. All rights reserved. NeuroRx1545-534334October 2006 © 2006 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.journals.elsevierhealth.com/periodicals/nurx/article/PIIS1545534306001404/abstract?rss=yesEditorial Board10.1016/S1545-5343(06)00140-4NeuroRx 3, 4 (2006)2006-10-01NeuroRx2006-10-0134S1545-5343(06)X0005-6iihttp://www.journals.elsevierhealth.com/periodicals/nurx/article/PIIS1545534306001362/abstract?rss=yesIn January 2007, the name of the journal will be changed from NeuroRx® to Neurotherapeutics. When the original journal was titled as NeuroRx® and approved by the ASENT Board of Directors, we intended that it would serve as a shorthand version of “Neurotherapeutics.” Despite the success of the journal, questions about the title had been raised by members of the Editorial Board and the ASENT Board. Primarily, these concerns were that the name seemed more appropriate to a newsletter or to a less substantial publication, and did not adequately convey the focus of either the journal or its sponsoring society. Subsequent discussions at meetings of the Editorial Board and ASENT Board over the past year have reinforced the view that a name change to Neurotherapeutics would more clearly reflect the intended meaning of the journal title and would also, importantly, place it in a better strategic position for its future success.Changing the Name of the JournalAlan I. Faden10.1016/j.nurx.2006.08.002NeuroRx 3, 4 (2006)2006-10-01NeuroRx2006-10-0134S1545-5343(06)X0005-6EDITORIALS417417http://www.journals.elsevierhealth.com/periodicals/nurx/article/PIIS1545534306001349/abstract?rss=yesYour guest editors for this issue received their graduate educations in neuroscience in the 1970s. We find it astonishing how much of what was then taught as fact or principle has since been proved wrong: Dale’s law, for example (one neuron: one neurotransmitter), or the idea that gap junctions are rare and unimportant in the mammalian CNS. Diffusible neurotransmitters were unknown. Most spectacularly wrong was the dogma that plasticity and regeneration in the mammalian CNS vanish with maturation—that, once lesioned, the adult CNS structural and functional deficits are fixed and immutable.Translational Issues in NeurorehabilitationMichael Chopp, Michael Weinrich10.1016/j.nurx.2006.07.012NeuroRx 3, 4 (2006)2006-10-01NeuroRx2006-10-0134S1545-5343(06)X0005-6EDITORIALS418419http://www.journals.elsevierhealth.com/periodicals/nurx/article/PIIS1545534306001283/abstract?rss=yesSummary: Over the past 20 years, evidence has mounted regarding the capacity of the central nervous system to alter its structure and function throughout life. Injury to the central nervous system appears to be a particularly potent trigger for plastic mechanisms to be elicited. Following focal injury, widespread neurophysiological and neuroanatomical changes occur both in the peri-infarct region, as well as throughout the ipsi- and contralesional cortex, in a complex, time-dependent cascade. Since such post-injury plasticity can be both adaptive or maladaptive, current research is directed at understanding how plasticity may be modulated to develop more effective therapeutic interventions for neurological disorders, such as stroke. Behavioral training appears to be a significant contributor to adaptive plasticity after injury, providing a neuroscientific foundation for the development of physical therapeutic approaches. Adjuvant therapies, such as pharmacological agents and exogenous electrical stimulation, may provide a more receptive environment through which behavioral therapies may be imparted. This chapter reviews some of the recent results from animal models of injury and recovery that depict the complex time course of plasticity following cortical injury and implications for neurorehabilitation. PlasticityRandolph J. Nudo10.1016/j.nurx.2006.07.006NeuroRx 3, 4 (2006)2006-10-01NeuroRx2006-10-0134S1545-5343(06)X0005-6REVIEW ARTICLES420427http://www.journals.elsevierhealth.com/periodicals/nurx/article/PIIS154553430600126X/abstract?rss=yesSummary: Therapeutic activity is a mainstay of clinical neurorehabilitation, but is typically unstructured and directed at compensation rather than restoration of central nervous system function. Newer activity-based therapies (ABTs) are in early stages of development and testing. The ABTs attempt to restore function via standardized therapeutic activity based on principles of experimental psychology, exercise physiology, and neuroscience. Three of the best developed ABTs are constraint-induced therapy, robotic therapy directed at the hemiplegic arm, and treadmill training techniques aimed at improving gait in persons with stroke and spinal cord injury. These treatments appear effective in improving arm function and gait, but they have not yet been clearly demonstrated to be more effective than equal amounts of traditional techniques. Resistance training is clearly demonstrated to improve strength in persons with stroke and brain injury, and most studies show that it does not increase hypertonia. Clinical trials of ABTs face several methodological challenges. These challenges include defining dosage, standardizing treatment parameters across subjects and within treatment sessions, and determining what constitutes clinically significant treatment effects. The long-term goal is to develop prescriptive ABT, where specific activities are proven to treat specific motor system disorders. Activity-based therapies are not a cure, but are likely to play an important role in future treatment cocktails for stroke and spinal cord injury. Activity-Based TherapiesAlexander W. Dromerick, Peter S. Lum, Joseph Hidler10.1016/j.nurx.2006.07.004NeuroRx 3, 4 (2006)2006-10-01NeuroRx2006-10-0134S1545-5343(06)X0005-6REVIEW ARTICLES428438http://www.journals.elsevierhealth.com/periodicals/nurx/article/PIIS1545534306001337/abstract?rss=yesSummary: Stroke is a leading cause of disability that results not only in persistent neurological deficits, but also profound physical deconditioning that propagates disability and worsens cardiovascular risk. The potential for exercise-mediated adaptations to improve function, fitness, and cardiovascular health after stroke has been underestimated: it represents an emerging arena in neurotherapeutics. To define the health rationale for cardiovascular (aerobic) exercise, we first outline the impact of debilitating secondary biological changes in muscle and body composition on fitness and metabolic health after stroke. We provide an overview of evidence-based advances in exercise therapeutics, with a focus on task-oriented models that combine a progressive aerobic conditioning stimulus with motor learning to improve multiple physiological domains that determine longitudinal outcomes after stroke. Although progress in development of safe and effective exercise strategies is advancing, fundamental questions regarding dose intensity, prescription to optimize central and peripheral neuromuscular adaptations, and the public health value of exercise in secondary stroke prevention remain unanswered. Key issues steering future research in exercise neurotherapeutics are discussed within the context of initiatives to facilitate translation to community-based studies, requisite for dissemination. Exercise Rehabilitation After StrokeFrederick M. Ivey, Charlene E. Hafer-Macko, Richard F. Macko10.1016/j.nurx.2006.07.011NeuroRx 3, 4 (2006)2006-10-01NeuroRx2006-10-0134S1545-5343(06)X0005-6REVIEW ARTICLES439450http://www.journals.elsevierhealth.com/periodicals/nurx/article/PIIS1545534306001325/abstract?rss=yesSummary: There are complex relationships among behavioral experience, brain morphology, and functional recovery of an animal before and after brain injury. A large series of experimental studies have shown that exogenous manipulation of central neurotransmitter levels can directly affect plastic changes in the brain and can modulate the effects of experience and training. These complex relationships provide a formidable challenge for studies aimed at understanding neurotransmitter effects on the recovery process. Experiments delineating norepinephrine-modulated locomotor recovery after injury to the cerebral cortex illustrate the close relationships among neurotransmitter levels, brain plasticity, and behavioral recovery. Understanding the neurobiological processes underlying recovery, and how they might be manipulated, may lead to novel strategies for improving recovery from stroke-related gait impairment in humans. Neurotransmitters and Motor Activity: Effects on Functional Recovery after Brain InjuryLarry B. Goldstein10.1016/j.nurx.2006.07.010NeuroRx 3, 4 (2006)2006-10-01NeuroRx2006-10-0134S1545-5343(06)X0005-6REVIEW ARTICLES451457http://www.journals.elsevierhealth.com/periodicals/nurx/article/PIIS1545534306001374/abstract?rss=yesSummary: Current options for the treatment of stroke are extremely limited, partly because of the rapidity with which brain cells die when deprived of their blood supply. Several recent studies suggest that growth factors can produce improvement in animal models of stroke, even when administered at postischemic intervals of many hours to days, when conventional neuroprotective approaches are typically futile. Several growth factors can access the brain after systemic administration, making them more attractive as therapeutic agents. Finally, growth factors are key mediators of neurogenesis in the adult brain, which could have a role in brain repair and functional recovery following stroke. Growth Factors and StrokeDavid A. Greenberg, Kunlin Jin10.1016/j.nurx.2006.08.003NeuroRx 3, 4 (2006)2006-10-01NeuroRx2006-10-0134S1545-5343(06)X0005-6REVIEW ARTICLES458465http://www.journals.elsevierhealth.com/periodicals/nurx/article/PIIS1545534306001295/abstract?rss=yesSummary: There is a compelling need to develop cell and pharmacological therapeutic approaches to be administered beyond the hyperacute phase of stroke. These therapies capitalize on the capacity of the brain for neuroregeneration and neuroplasticity and are designed to reduce neurological deficits after stroke. This review provides an update of bone marrow–derived mesenchymal stem cells (MSCs) and select pharmacological agents in clinical use for other indications that promote the recovery process in the subacute and chronic phases after stroke. Among these agents are 3-hydroxy-3-methylglutaryl–coenzyme A reductase inhibitors (statins), erythropoietin (EPO), and phosphodiesterase type 5 (PDE-5) inhibitors and nitric oxide (NO) donors. Both the MSCs and the pharmacologic agents potentiate brain plasticity and neurobehavioral recovery after stroke. Neurorestorative Treatment of Stroke: Cell and Pharmacological ApproachesJieli Chen, Michael Chopp10.1016/j.nurx.2006.07.007NeuroRx 3, 4 (2006)2006-10-01NeuroRx2006-10-0134S1545-5343(06)X0005-6REVIEW ARTICLES466473http://www.journals.elsevierhealth.com/periodicals/nurx/article/PIIS1545534306001301/abstract?rss=yesSummary: Stroke is a common disorder that produces a major burden to society, largely through long-lasting motor disability in survivors. Recent studies have broadened our understanding of the processes underlying recovery of motor function after stroke. Bilateral motor regions of the brain experience substantial reorganization after stroke, including changes in the strength of interhemispheric inhibitory interactions. Our understanding of the extent to which different forms of reorganization contribute to behavioral gains in the rehabilitative process, although still limited, has led to the formulation of novel interventional strategies to regain motor function. Transcranial magnetic (TMS) and DC (tDCS) electrical stimulation are noninvasive brain stimulation techniques that modulate cortical excitability in both healthy individuals and stroke patients. These techniques can enhance the effect of training on performance of various motor tasks, including those that mimic activities of daily living. This review looks at the effects of TMS and tDCS on motor cortical function and motor performance in healthy volunteers and in patients with stroke. Both techniques can either enhance or suppress cortical excitability, and may move to the clinical arena as strategies to enhance the beneficial effects of customarily used neurorehabilitative treatments after stroke. Noninvasive Brain Stimulation in Stroke RehabilitationBrian R. Webster, Pablo A. Celnik, Leonardo G. Cohen10.1016/j.nurx.2006.07.008NeuroRx 3, 4 (2006)2006-10-01NeuroRx2006-10-0134S1545-5343(06)X0005-6REVIEW ARTICLES474481http://www.journals.elsevierhealth.com/periodicals/nurx/article/PIIS1545534306001258/abstract?rss=yesSummary: Most patients show improvement in the weeks or months after a stroke. Recovery is incomplete, however, leaving most with significant impairment and disability. Because the brain does not grow back to an appreciable extent, this recovery occurs on the basis of change in function of surviving tissues. Brain mapping studies have characterized a number of processes and principles relevant to recovery from stroke in humans. The findings have potential application to improving therapeutics that aim to restore function after stroke. Imaging Motor Recovery After StrokeNuray Yozbatiran, Steven C. Cramer10.1016/j.nurx.2006.07.003NeuroRx 3, 4 (2006)2006-10-01NeuroRx2006-10-0134S1545-5343(06)X0005-6REVIEW ARTICLES482488http://www.journals.elsevierhealth.com/periodicals/nurx/article/PIIS1545534306001271/abstract?rss=yesSummary: Two–photon microscopy (TPM) has become an increasingly important tool for imaging the structure and function of brain cells in living animals. TPM imaging studies of neuronal structures over intervals ranging from seconds to years have begun to provide important insights into the structural plasticity of synapses and the modulating effects of experience in the intact brain. TPM has also started to reveal how neuronal connections are altered in animal models of neurodegeneration, acute brain injury, and cerebrovascular disease. Here, we review some of these studies with special emphasis on the degree of structural dynamism of postsynaptic dendritic spines in the adult mouse brain as well as synaptic pathology in mouse models of Alzheimer’s disease and cerebral ischemia. We also discuss technical considerations that are critical for the acquisition and interpretation of data from TPM in vivo. Two-photon Imaging of Synaptic Plasticity and Pathology in the Living Mouse BrainJaime Grutzendler, Wen-Biao Gan10.1016/j.nurx.2006.07.005NeuroRx 3, 4 (2006)2006-10-01NeuroRx2006-10-0134S1545-5343(06)X0005-6REVIEW ARTICLES489496http://www.journals.elsevierhealth.com/periodicals/nurx/article/PIIS1545534306001350/abstract?rss=yesSummary: Select functional outcome tests commonly used for evaluating sensorimotor and cognitive capacity in rodents with focal intracerebral ischemic or hemorrhagic injury are described, along with upgrades and issues of concern for translational research. An emphasis is placed on careful quantitative and qualitative assessment of acute and long-term behavioral deficits, and on avoidance of frequent pitfalls. Methods for detecting different degrees of injury and treatment-related improvements are included. Determining the true potential of an intervention requires a set of behavioral analyses that can monitor compensatory learning. In a number of preclinical outcome tests, animals can develop remarkably effective “tricks” that are difficult to detect but frequently lead to dramatic improvements in performance, particularly with repeated practice. However, some interventions may facilitate learning without promoting brain repair, but these may not translate into a meaningful level of benefit in the clinic. Additionally, it is important to determine whether there are any preinjury functional asymmetries in order to accurately assess damage-related changes in behavior. This is illustrated by the fact that some animals have chronic endogenous asymmetries and that others, albeit infrequently, can sustain a spontaneous cerebral stroke, without any experimental induction, that can lead to chronic deficits as reflected by behavioral, imaging, and histological analyses. Finally, a useful new modification of the water maze that involves moving the platform from trial to trial within the target quadrant is reviewed, and its advantages over the standard version are discussed. Behavioral Tests for Preclinical Intervention AssessmentTimothy Schallert10.1016/j.nurx.2006.08.001NeuroRx 3, 4 (2006)2006-10-01NeuroRx2006-10-0134S1545-5343(06)X0005-6REVIEW ARTICLES497504http://www.journals.elsevierhealth.com/periodicals/nurx/article/PIIS1545534306001313/abstract?rss=yesSummary: Most patients who survive a stroke experience some degree of physical recovery. Selecting the appropriate outcome measure to assess physical recovery is a difficult task, given the heterogeneity of stroke etiology, symptoms, severity, and even recovery itself. Despite these complexities, a number of strategies can facilitate the selection of functional outcome measures in stroke clinical trial research and practice. Clinical relevance in stroke outcome measures can be optimized by incorporating a framework of health and disability, such as the International Classification of Functioning, Disability, and Health (ICF). The ICF provides the conceptual basis for measurement and policy formulations for disability and health assessment. All outcome measures selected should also have sound psychometric properties. The essential psychometric properties are reliability, validity, responsiveness, sensibility, and established minimal clinically important difference. It is also important to establish the purpose of the measurement (discriminative, predictive, or evaluative) and to determine whether the purpose of the study is to evaluate the efficacy or effectiveness of an intervention. In addition, when selecting outcome measures and time of assessment, the natural history of stroke and stroke severity must be regarded. Finally, methods for acquiring data must also be considered. We present a comprehensive overview of the issues in selecting stroke outcome measures and characterize existing measures relative to these issues. Issues in Selecting Outcome Measures to Assess Functional Recovery After StrokeSharon Barak, Pamela W. Duncan10.1016/j.nurx.2006.07.009NeuroRx 3, 4 (2006)2006-10-01NeuroRx2006-10-0134S1545-5343(06)X0005-6REVIEW ARTICLES505524http://www.journals.elsevierhealth.com/periodicals/nurx/article/PIIS1545534306001246/abstract?rss=yesSummary: Over the past decade, community neurorehabilitation has emerged as a promising extension of neurological rehabilitation. The goal of community neurorehabilitation is to maximize functional ability and quality of life through multidimensional rehabilitation that occurs while the individual is living in a home versus acute or transitory care setting. Because of its multidisciplinary focus, many variations of community neurorehabilitation teams have been implemented. Critical gaps exist, however, in understanding of the influence of structural and procedural differences among programs, as well as patient level variables such as social support, on recovery. This paper examines the current evidence of the effectiveness of community neurorehabilitation through a review of the findings of systematic reviews and meta-analyses of four neurological conditions: stroke, multiple sclerosis, traumatic brain injury, and Parkinson’s disease. It focuses in particular on the data regarding physical therapy and occupational therapy, which are two of the primary components of community neurorehabilitation programs. Community Neurorehabilitation: A Synthesis of Current Evidence and Future Research DirectionsSarah E. Chard10.1016/j.nurx.2006.07.002NeuroRx 3, 4 (2006)2006-10-01NeuroRx2006-10-0134S1545-5343(06)X0005-6REVIEW ARTICLES525534http://www.journals.elsevierhealth.com/periodicals/nurx/article/PIIS1545534306001234/abstract?rss=yesSpinal muscular atrophy (SMA) is an inherited neuromuscular disease and the leading genetic killer of infants and toddlers. The human toll of this disease, combined with its unique genetic profile, has focused attention from the National Institutes of Health, industry, academia, and advocacy organizations on making a treatment available by 2010. Indeed, SMA was selected in 2003 by the National Institute of Neurological Disorders and Stroke (NINDS) for a model translational research program aimed at accelerating drug discovery efforts against neurodegenerative diseases through a collaborative process involving all stakeholders. This program responds to the need for an increased focus on treating rare diseases. About 10% of the 6000 to 7000 recognized rare diseases are neurological, yet of the more than 200 drugs and biological products for orphan diseases that have been introduced since 1983, only a handful were for neurological diseases. Spinal muscular atrophy was chosen as the prototype because scientists believe it is one of the closest to a cure and because of a belief that research aimed at finding treatments for SMA will shed light on treatments for other neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and Parkinson’s, Alzheimer’s, and Huntington’s disease.Spinal Muscular Atrophy: A Test Case for Drug Development in Orphan DiseasesLisa J. Bain10.1016/j.nurx.2006.07.001NeuroRx 3, 4 (2006)2006-10-01NeuroRx2006-10-0134S1545-5343(06)X0005-6SUMMARY OF THE PATIENT ADVOCACY PRE-MEETING535539http://www.journals.elsevierhealth.com/periodicals/nurx/article/PIIS1545534306001532/abstract?rss=yesAt the Advocacy Forum at the Eighth Annual Meeting of the American Society for Experimental NeuroTherapeutics (ASENT), “Drug Development in Critical Times: The Role of Patient Advocates,” it became clear that patients and patient advocates, in addition to federal regulatory agencies, academic scientists, and the pharmaceutical industry, all play essential roles in drug development. Moreover, a strong yet flexible network among all of these stakeholders is emerging, which has the potential to propel drug development forward at a rapid pace, even for orphan diseases. This network is, of necessity, centered on patients, who provide not only motivation and the evidence of a clinical benefit if it is achieved, but are also key participants at all stages of the drug development pathway.Drug Development in Critical TimesLisa J. Bain10.1016/j.nurx.2006.08.004NeuroRx 3, 4 (2006)2006-10-01NeuroRx2006-10-0134S1545-5343(06)X0005-6ADVOCACY FORUM REPORT540543http://www.journals.elsevierhealth.com/periodicals/nurx/article/PIIS1545534306001490/abstract?rss=yesAuthor index10.1016/S1545-5343(06)00149-0NeuroRx 3, 4 (2006)2006-10-01NeuroRx2006-10-0134S1545-5343(06)X0005-6544544http://www.journals.elsevierhealth.com/periodicals/nurx/article/PIIS1545534306001507/abstract?rss=yesSubject index10.1016/S1545-5343(06)00150-7NeuroRx 3, 4 (2006)2006-10-01NeuroRx2006-10-0134S1545-5343(06)X0005-6545547