Posts Tagged plasticity

[Abstract] Polarity-independent effects of tDCS on paired associative stimulation-induced plasticity

Abstract

Background

Transcranial direct current stimulation (tDCS) can polarize the cortex of the human brain.

Objective

/Hypothesis: We sought to verify the hypothesis that posterior-anterior (PA) but not anterior-posterior (AP) tDCS of primary motor cortex (M1) produces cooperative effects with corticospinal plasticity induced by paired associative stimulation of the supplementary motor area (SMA) to M1 projection (PASSMA→M1) in a highly controlled experimental design.

Methods

Three experimental conditions were tested in a double-blinded, randomized crossover design in 15 healthy adults: Navigated PASSMA→M1 during PA-tDCS (35 cm2 electrodes, anode 3 cm posterior to M1 hand area, cathode over contralateral frontopolar cortex, 1 mA, 2 × 5 min) or AP-tDCS (reversed polarity), or sham-tDCS. Effects were analyzed over 120 min post-intervention by changes of motor evoked potential (MEP) amplitude in a hand muscle.

Results

There was no significant effect of tDCS on PASSMA→M1 induced plasticity in the repeated-measures ANOVA. However, post-hoc within-subject contrasts revealed a significant tDCS with PASSMA→M1 interaction. This was explained by PA-tDCS and AP-tDCS modifying the PASSMA→M1 effect into the same direction in 13/15 subjects (87%, p = 0.004 for deviation from equality). Sizes of the PA-tDCS and AP-tDCS effects were correlated (rs = 0.53, p = 0.044). A control experiment demonstrated that PA-tDCS and AP-tDCS alone (without PASSMA→M1) had no effect on MEP amplitude.

Conclusions

Data point to unidirectional tDCS effects on PASSMA→M1 induced plasticity irrespective of tDCS polarity, in contrast to our hypothesis. We propose that radial symmetry of cortical columns, gyral geometry of motor cortex, and cooperativity of plasticity induction can explain the findings.

Source: Polarity-independent effects of tDCS on paired associative stimulation-induced plasticity

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[Abstract] Virtual Reality and Serious Games in Neurorehabilitation of Children and Adults: Prevention, Plasticity, and Participation

Use of virtual reality (VR) and serious games (SGs) interventions within rehabilitation as motivating tools for task specific training for individuals with neurological conditions are fast-developing. Within this perspective paper we use the framework of the IV STEP conference to summarize the literature on VR and SG for children and adults by three topics: Prevention; Outcomes: Body-Function-Structure, Activity and Participation; and Plasticity. Overall the literature in this area offers support for use of VR and SGs to improve body functions and to some extent activity domain outcomes. Critical analysis of clients’ goals and selective evaluation of VR and SGs are necessary to appropriately take advantage of these tools within intervention. Further research on prevention, participation, and plasticity is warranted. We offer suggestions for bridging the gap between research and practice integrating VR and SGs into physical therapist education and practice.

Source: Virtual Reality and Serious Games in Neurorehabilitation of… : Pediatric Physical Therapy

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[ARTICLE] Diffusion MRI and the detection of alterations following traumatic brain injury – Full Text

Abstract

This article provides a review of brain tissue alterations that may be detectable using diffusion magnetic resonance imaging MRI (dMRI) approaches and an overview and perspective on the modern dMRI toolkits for characterizing alterations that follow traumatic brain injury (TBI). Noninvasive imaging is a cornerstone of clinical treatment of TBI and has become increasingly used for preclinical and basic research studies. In particular, quantitative MRI methods have the potential to distinguish and evaluate the complex collection of neurobiological responses to TBI arising from pathology, neuroprotection, and recovery. dMRI provides unique information about the physical environment in tissue and can be used to probe physiological, architectural, and microstructural features. Although well-established approaches such as diffusion tensor imaging are known to be highly sensitive to changes in the tissue environment, more advanced dMRI techniques have been developed that may offer increased specificity or new information for describing abnormalities. These tools are promising, but incompletely understood in the context of TBI. Furthermore, model dependencies and relative limitations may impact the implementation of these approaches and the interpretation of abnormalities in their metrics. The objective of this paper is to present a basic review and comparison across dMRI methods as they pertain to the detection of the most commonly observed tissue and cellular alterations following TBI.

1 INTRODUCTION

Despite the long history of traumatic brain injury (TBI) as a prevalent cause of death and disability in humans, defining the neurobiological underpinnings of damage and recovery following TBI remains a central challenge. The complex collection of physiological, cellular, and molecular changes that follow TBI can appear to be remarkably heterogeneous, but at the same time they are highly organized into coordinated responses such as neurodegeneration, inflammation, and regeneration. The corpus of histological studies spanning a variety of experimental animal models of TBI have provided crucial insights about the pathomechanisms and cellular alterations that accompany posttraumatic tissue change, but considerable work remains to determine the spatiotemporal evolution of abnormalities, interrelationships among different tissue responses, and their impact on health and behavioral outcomes. Noninvasive imaging in animal models has the potential to build on what is known from histology by providing longitudinal and whole-brain information, but for this approach to be successful it is essential to first improve the understanding of how imaging abnormalities correspond to tissue and cellular changes.

Diffusion magnetic resonance imaging (dMRI) methods are particularly promising for the development of imaging markers of TBI pathology because they are sensitive to microscale water displacement as a proxy for tissue environment geometry and provide a range of quantitative scalar metrics across the whole brain. Furthermore, dMRI may be combined with other conventional or advanced magnetic resonance imaging (MRI) methods such as arterial spin labeling, susceptibility-weighted imaging, or a variety of contrast agent MRI approaches to provide complementary and comprehensive outcome measures. Standard dMRI methods and especially diffusion tensor imaging (DTI) have already demonstrated sensitive detection of abnormalities in a number of experimental models of TBI. In the past decade, multiple advanced dMRI approaches have extended beyond the conventional models with the goals of improving the physical description of water diffusion (e.g., by modeling “non-Gaussian” diffusion) or parameterizing dMRI with respect to the expected biological environment (e.g., by modeling cellular compartments and/or fiber geometry). These new tools will be valuable if they are able to improve the sensitivity or specificity of dMRI following TBI; however, we lack a systematic understanding of how dMRI methods differ from one another for detecting and describing tissue alterations.

A number of excellent reviews exist to describe the current understanding of cellular mechanisms of TBI in general (Bramlett & Dietrich, 2015; Pekna & Pekny, 2012) and within particular areas of neurobiology including neurodegeneration (Johnson, Stewart, & Smith, 2013; Stoica & Faden, 2010), inflammation (Burda, Bernstein, & Sofroniew, 2016; Ziebell & Morganti-Kossmann, 2010), and myelin changes (Armstrong, Mierzwa, Marion, & Sullivan, 2016), among others. As well, several existing reviews have been published regarding MRI and DTI to study human TBI (Brody, Mac Donald, & Shimony, 2015; Duhaime et al., 2010; Hulkower, Poliak, Rosenbaum, Zimmerman, & Lipton, 2013), and recently a pertinent overview and summary of advanced dMRI tools and their relevance to clinical outcomes was published (Douglas et al., 2015). The focus of the present review is to combine what is known from work in experimental models of TBI about tissue and cellular alterations that may affect the physical tissue environment with a comparative description of the major methods for dMRI that may be differentially sensitive to TBI-related tissue change alongside several important caveats for their use and interpretation. The first section provides a categorical summary of cellular response to trauma, emphasizing alterations with microstructural, architectural, or neuroanatomical manifestations that may give rise to detectable dMRI abnormalities, including a review of the existing dMRI studies in experimental TBI models. The second section contains a comparative overview of presently available dMRI methods from standard approaches to advanced techniques. The objective of this article is to provide a reference for the current understanding of these topics as well as a perspective to help guide selection of dMRI tools based on particular aspects of TBI questions.

Continue —> Diffusion MRI and the detection of alterations following traumatic brain injury – Hutchinson – 2017 – Journal of Neuroscience Research – Wiley Online Library

Figure 2. Cross-model comparison of scalar maps in the injured brain. A range of tissue and injury-related contrasts may be visually observed in this collage of 16 representative metrics in the same slice from different dMRI models. This cross-model view of scalar maps demonstrates the potential for nonredundant information about regions of injury that may be gleaned from different models. DTI metrics of fractional anisotropy (FA), trace (TR), axial and radial diffusivity (Dax and Drad), directionally encoded color (DEC) map weighted by lattice index, DEC weighted by Westin linear anisotropy (WL) and DEC weighted by Westin planar anisotropy (WP), DKI metrics of mean kurtosis (MK), axial and radial kurtosis (AK and RK) and kurtosis FA (KFA), MAP-MRI metrics of return to the origin, axis, and plane probabilities (RTOP, RTAP, and RTPP), propagator anisotropy (PA) and non-Gaussianity (NG) and NODDI metrics of compartment volume fractions for isotropic free water (Viso), intracellular water (Vic) and intracellular restricted water (Vir), and orientation dispersion index (ODI). Insets of each map show tissue near the injury site where dMRI values are expected to be abnormal.

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[ARTICLE] Neuroplastic Changes Following Brain Ischemia and their Contribution to Stroke Recovery: Novel Approaches in Neurorehabilitation – Full Text

Ischemic damage to the brain triggers substantial reorganization of spared areas and pathways, which is associated with limited, spontaneous restoration of function. A better understanding of this plastic remodeling is crucial to develop more effective strategies for stroke rehabilitation. In this review article, we discuss advances in the comprehension of post-stroke network reorganization in patients and animal models. We first focus on rodent studies that have shed light on the mechanisms underlying neuronal remodeling in the perilesional area and contralesional hemisphere after motor cortex infarcts. Analysis of electrophysiological data has demonstrated brain-wide alterations in functional connectivity in both hemispheres, well beyond the infarcted area. We then illustrate the potential use of non-invasive brain stimulation (NIBS) techniques to boost recovery. We finally discuss rehabilitative protocols based on robotic devices as a tool to promote endogenous plasticity and functional restoration.

Introduction

Following an ischemic insult within the motor cortex, one or more body parts contralateral to the infarct result impaired or paretic. The degree of the motor impairment depends on many factors, such as the extent of the infarct, the identity of the damaged region(s) and the effectiveness of the early medical care. Substantial functional recovery can occur in the first weeks after stroke, mainly due to spontaneous mechanisms (Kwakkel et al., 2004; Cramer, 2008; Darling et al., 2011; Ward, 2011; Grefkes and Fink, 2014). About 26% of stroke survivors are able to carry on everyday activities (Activity of Daily Living or ADLs, i.e., eating, drinking, walking, dressing, bathing, cooking, writing) without any help, but another 26% is forced to shelter in a nursing home (Carmichael, 2005). Impairments of upper and lower limbs are particularly disabling as they impact on the degree of independence in ADLs. Overall, a significant percentage of the patients exhibit persistent disability following ischemic attacks. Therefore, it is critical to increase our knowledge of post-stroke neuroplasticity for implementing novel rehabilitative strategies. In this review we summarize data about plastic reorganizations after injury, both in the ipsilesional and contralesional hemisphere. We also describe non-invasive brain stimulation (NIBS) techniques and robotic devices for stimulating functional recovery in humans and rodent stroke models.

Neuroplasticity After Stroke

The term brain plasticity defines all the modifications in the organization of neural components occurring in the central nervous system during the entire life span of an individual (Sale et al., 2009). Such changes are thought to be highly involved in mechanisms of aging, adaptation to environment and learning. Moreover, neuronal plastic phenomena are likely to be at the basis of adaptive modifications in response to anatomical or functional deficit or brain damage (Nudo, 2006). Ischemic damage causes a dramatic alteration of the entire complex neural network within the affected area. It has been amply demonstrated, by many studies, that the cerebral cortex exhibits spontaneous phenomena of brain plasticity in response to damage (Gerloff et al., 2006; Nudo, 2007). The destruction of neural networks indeed stimulates a reorganization of the connections and this rewiring is highly sensitive to the experience following the damage (Stroemer et al., 1993; Li and Carmichael, 2006). Such plastic phenomena involve particularly the perilesional tissue in the injured hemisphere, but also the contralateral hemisphere, subcortical and spinal regions.

Continue —> Frontiers | Neuroplastic Changes Following Brain Ischemia and their Contribution to Stroke Recovery: Novel Approaches in Neurorehabilitation | Frontiers in Cellular Neuroscience

Figure 3. Example of a novel robotic system that integrates functional grasping, active reaching arm training and bimanual tasks. An example of a novel robotic system that integrates functional grasping, active reaching arm training and bimanual tasks, consisting of: (i) Virtual Reality: software applications composed of rehabilitative and evaluation tasks; (ii) TrackHold: robotic device to support the weight of the user’s limb during tasks execution; (iii) Robotic Hand Exos: active hand exoskeleton to assist grasping tasks; and (iv) Handgrip sensors to support the bilateral grasping training and evaluation (modified from Sgherri et al., 2017).

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[Abstract] Neurosurgery and Music; The effect of Wolfgang Amadeus Mozart

Abstract

Background

The nervous system works like a great orchestra. Specially the music of Mozart with its´ “Mozart´s effect” is appropriate to use in neurosurgery. The paper investigates the relationship between music and neurosurgery, Mozart´s music in neurosurgical practice.

Material and Methods

We used digital catalogues like “pubmed” as well as the libraries of universities. Key words were “Wolfgang Amadeus Mozart”, “neurosurgery and music”.

Results

At the first half of 20 century, neurosurgical approach of some musicians have resulted with fatal outcome such as Maurice Ravel, Josef Hassid,George Gershwin. The cause of this is probably that neurosurgery has not been developed yet in the first half of the 20th century. In last three decades, the neurosurgical operations of musician show that musicians has rich associations between auditory, somatic, and sensorial systems.

Conclusion

It is clear that we have much to learn from studies about music and brain function that derive from our surgical experiences with patients. The neuronal plasticity of musician‘s brain may be different than non-musicians´. Musicians with enhanced motor skills have greater capacity for plasticity because of enriched interhemispheric connections. Listening music, and of Mozart´s effect in neurosurgical practice, intensive care, or rehabilitation was documented in much studies. As authors, we mean something different: Its effectiveness shouldbe studied. We can concluded that, in current neurosurgical practice that Mozart has an effect. More research and clinical studies are needed.

Source: Neurosurgery and Music; The effect of Wolfgang Amadeus Mozart

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[BLOG POST] Brain Plasticity: How Adult Born Neurons Get Wired – Neuroscience News

FEBRUARY 3, 2017

Summary: Researchers report adult neurogenesis not only helps increase the number of cells in a neural network, it also promotes plasticity in the existing network. Additionally, they have identified the role the Bax gene plays in synaptic pruning.

Source: University of Alabama at Birmingham.

One goal in neurobiology is to understand how the flow of electrical signals through brain circuits gives rise to perception, action, thought, learning and memories.

Linda Overstreet-Wadiche, Ph.D., and Jacques Wadiche, Ph.D., both associate professors in the University of Alabama at Birmingham Department of Neurobiology, have published their latest contribution in this effort, focused on a part of the brain that helps form memories — the dentate gyrus of the hippocampus.

The dentate gyrus is one of just two areas in the brain where new neurons are continuously formed in adults. When a new granule cell neuron is made in the dentate gyrus, it needs to get ‘wired in,’ by forming synapses, or connections, in order to contribute to circuit function. Dentate granule cells are part of a circuit that receive electrical signals from the entorhinal cortex, a cortical brain region that processes sensory and spatial input from other areas of the brain. By combining this sensory and spatial information, the dentate gyrus can generate a unique memory of an experience.

Overstreet-Wadiche and UAB colleagues posed a basic question: Since the number of neurons in the dentate gyrus increases by neurogenesis while the number of neurons in the cortex remains the same, does the brain create additional synapses from the cortical neurons to the new granule cells, or do some cortical neurons transfer their connections from mature granule cells to the new granule cells?

Their answer, garnered through a series of electrophysiology, dendritic spine density and immunohistochemistry experiments with mice that were genetically altered to produce either more new neurons or kill off newborn neurons, supports the second model — some of the cortical neurons transfer their connections from mature granule cells to the new granule cells.

This opens the door to look at how this redistribution of synapses between the old and new neurons helps the dentate gyrus function. And it opens up tantalizing questions. Does this redistribution disrupt existing memories? How does this redistribution relate to the beneficial effects of exercise, which is a natural way to increase neurogenesis?

“Over the last 10 years there has been evidence supporting a redistribution of synapses between old and new neurons, possibly by a competitive process that the new cells tend to ‘win,’” Overstreet-Wadiche said. “Our findings are important because they directly demonstrate that, in order for new cells to win connections, the old cells lose connections. So, the process of adult neurogenesis not only adds new cells to the network, it promotes plasticity of the existing network.”

Image shows a brain.

The study opens the door to look at how this redistribution of synapses between the old and new neurons helps the dentate gyrus function. NeuroscienceNews.com image is for illustrative purposes only.

“It will be interesting to explore how neurogenesis-induced plasticity contributes to the function of this brain region,” she continued. “Neurogenesis is typically associated with improved acquisition of new information, but some studies have also suggested that neurogenesis promotes ‘forgetting’ of existing memories.”

The researchers also unexpectedly found that the Bax gene, known for its role in apoptosis, appears to also play a role in synaptic pruning in the dentate gyrus.

“There is mounting evidence that the cellular machinery that controls cell death also controls the strength and number of synaptic connections,” Overstreet-Wadiche said. “The appropriate balance of synapses strengthening and weakening, collectively termed synaptic plasticity, is critical for appropriate brain function. Hence, understanding how synaptic pruning occurs may shed light on neurodevelopmental disorders and on neurodegenerative diseases in which a synaptic pruning gone awry may contribute to pathological synapse loss.”

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

All of the work was performed in the Department of Neurobiology at UAB. In addition to Overstreet-Wadiche and Wadiche, co-authors of the paper, “Adult born neurons modify excitatory synaptic transmission to existing neurons,” published in eLife, are Elena W. Adlaf, Ryan J. Vaden, Anastasia J. Niver, Allison F. Manuel, Vincent C. Onyilo, Matheus T. Araujo, Cristina V. Dieni, Hai T. Vo and Gwendalyn D. King.

Much of the data came from the doctoral thesis research of Adlaf, a former UAB Neuroscience graduate student who is now a postdoctoral fellow at Duke University.

Funding: Funding for this research came from Civitan International Emerging Scholars awards, and National Institutes of Health awards or grants NS098553, NS064025, NS065920 and NS047466.

Source: Jeff Hansen – University of Alabama at Birmingham
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Full open access research for “Adult-born neurons modify excitatory synaptic transmission to existing neurons” by Elena W Adlaf, Ryan J Vaden, Anastasia J Niver, Allison F Manuel, Vincent C Onyilo, Matheus T Araujo, Cristina V Dieni, Hai T Vo, Gwendalyn D King, Jacques I Wadiche, and Linda Overstreet-Wadiche in eLife. Published online January 30 2017 doi:10.7554/eLife.19886

Birmingham “Brain Plasticity: How Adult Born Neurons Get Wired.” NeuroscienceNews. NeuroscienceNews, 3 February 2017.
<http://neurosciencenews.com/neuroplasticity-neuroscience-6053/&gt;.

Abstract

Did You Know How Loud Balloons Can Be?

Adult-born neurons are continually produced in the dentate gyrus but it is unclear whether synaptic integration of new neurons affects the pre-existing circuit. Here we investigated how manipulating neurogenesis in adult mice alters excitatory synaptic transmission to mature dentate neurons. Enhancing neurogenesis by conditional deletion of the pro-apoptotic gene Bax in stem cells reduced excitatory postsynaptic currents (EPSCs) and spine density in mature neurons, whereas genetic ablation of neurogenesis increased EPSCs in mature neurons. Unexpectedly, we found that Bax deletion in developing and mature dentate neurons increased EPSCs and prevented neurogenesis-induced synaptic suppression. Together these results show that neurogenesis modifies synaptic transmission to mature neurons in a manner consistent with a redistribution of pre-existing synapses to newly integrating neurons and that a non-apoptotic function of the Bax signaling pathway contributes to ongoing synaptic refinement within the dentate circuit.

“Adult-born neurons modify excitatory synaptic transmission to existing neurons” by Elena W Adlaf, Ryan J Vaden, Anastasia J Niver, Allison F Manuel, Vincent C Onyilo, Matheus T Araujo, Cristina V Dieni, Hai T Vo, Gwendalyn D King, Jacques I Wadiche, and Linda Overstreet-Wadiche in eLife. Published online January 30 2017 doi:10.7554/eLife.19886

Source: Brain Plasticity: How Adult Born Neurons Get Wired – Neuroscience News

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[Abstract] Neural plasticity during motor learning with motor imagery practice: Review and perspectives

Highlights

• TMS reveals the neural aspects of motor learning with MI.

• Neural plasticity during MI practice may occur at the cortical and spinal level.

• MI training may strengthen synapse efficiency.

• Presynaptic inhibition may decrease after MI training.


Abstract

In the last decade, many studies confirmed the benefits of mental practice with motor imagery. In this review we first aimed to compile data issued from fundamental and clinical investigations and to provide the key-components for the optimization of motor imagery strategy. We focused on transcranial magnetic stimulation studies, supported by brain imaging research, that sustain the current hypothesis of a functional link between cortical reorganization and behavioral improvement. As perspectives, we suggest a model of neural adaptation following mental practice, in which synapse conductivity and inhibitory mechanisms at the spinal level may also play an important role.

Source: Neural plasticity during motor learning with motor imagery practice: Review and perspectives

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[ARTICLE] Long-Term Plasticity in Reflex Excitability Induced by Five Weeks of Arm and Leg Cycling Training after Stroke – Full Text HTML

Abstract:

Neural connections remain partially viable after stroke, and access to these residual connections provides a substrate for training-induced plasticity. The objective of this project was to test if reflex excitability could be modified with arm and leg (A & L) cycling training. Nineteen individuals with chronic stroke (more than six months postlesion) performed 30 min of A & L cycling training three times a week for five weeks. Changes in reflex excitability were inferred from modulation of cutaneous and stretch reflexes. A multiple baseline (three pretests) within-subject control design was used. Plasticity in reflex excitability was determined as an increase in the conditioning effect of arm cycling on soleus stretch reflex amplitude on the more affected side, by the index of modulation, and by the modulation ratio between sides for cutaneous reflexes. In general, A & L cycling training induces plasticity and modifies reflex excitability after stroke.

1. Introduction

The arms and the legs are coupled in the human nervous system such that activity in the arms affects activity in the legs and vice versa. In quadrupeds, forelimb–hindlimb coordination is well documented and has been attributed to propriospinal linkages between cervical and lumbosacral spinal central pattern-generating networks [1,2,3,4,5,6]. Bipedal human locomotion is likely built upon elements of quadrupedal coordination [2,5], where it involves coordination of all four limbs. Only indirect evidence for quadrupedal locomotor linkages exists, however.
The modulation of reflex amplitudes can be used to probe for changes in interlimb neural activity [4,7]. Investigations of soleus stretch and H-reflex modulation during rhythmic arm movement provide evidence of neuronal coupling between the arms and the legs [2,3,8,9,10]. Examining cutaneous reflexes during rhythmic movements can also probe for interactions between the limbs. In this context, a widespread interlimb network is revealed by the extensive distribution of reflexes across many muscles in both the arms and the legs regardless of which limb is directly stimulated [4,11,12]. In addition, phase-dependent modulation found in muscles of all four limbs during rhythmic movement is suggestive of coupling between segmental spinal networks [12,13,14,15,16]. Regulation of rhythmic arm and leg movement is supported by somatosensory linkages in the form of interlimb reflexes [12,17,18] and neural coupling between lumbar and cervical spinal cord networks [10,19,20,21,22]. …

Figure 1. Illustration of the testing and training protocols. A multiple baseline within-subject control design was used for this study. An A & L cycle ergometer (Sci-Fit Pro 2) was used for training. The setups for stretch reflex and cutaneous reflex testing are shown. Muscles of interest are shown with a gray oval, and electrical stimulation is shown with a black lightning bolt. For the stretch reflex setup, a brief vibration was delivered to the triceps surae tendon and the reflex was recorded from the soleus (SOL) muscle, separately for each side. For the cutaneous reflex setup, simultaneous electrical stimulation was applied to the superficial radial (SR) and the superficial peroneal (SP) nerves, and reflexes were recorded bilaterally from the soleus (SOL), tibialis anterior (TA), flexor carpi radialis (FCR), and the posterior deltoid (PD) muscles.

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[WEB SITE] Scientists discover neuron-producing stem cells in the membranes covering the brain

Credit: Heidi Cartwright, Wellcome Images

 

Discovery brings with it possible implications for brain regeneration –

In a cross-domain study directed by professor Peter Carmeliet (VIB – KU Leuven), researchers discovered unexpected cells in the protective membranes that enclose the brain, the so called meninges. These ‘neural progenitors’ (stem cells that differentiate into different kinds of neurons) are produced during embryonic development.

See Also: Stem cells in the brain: Limited self-renewal

These findings show that the neural progenitors found in the meninges produce new neurons after birth, highlighting the importance of meningeal tissue as well as these cells’ potential in the development of new therapies for brain damage or neurodegeneration. A paper highlighting the results is published in the journal Cell Stem Cell.

Scientists’ understanding of brain plasticity, or the ability of the brain to grow, develop, recover from injuries and adapt to changing conditions throughout our lives, has been greatly broadened in recent years. Before the discoveries of the last few decades, neurologists once thought that the brain became ‘static’ after childhood. This dogma has changed, with researchers finding more and more evidence that the brain is capable of healing and regenerating in adulthood, thanks to the presence of stem cells. However, neuronal stem cells were generally believed to only reside within the brain tissue, not in the membranes surrounding it.

The meninges: unappreciated no more

Believed in the past to serve a mainly protective function to dampen mechanical shocks, the meninges have been historically underappreciated by science as having neurological importance in its own right. The data gathered by the team challenges the current idea that neural precursors—or stem cells that give rise to neurons—can only be found inside actual brain tissue.

Learn More: Scientists sniff out unexpected role for stem cells in the brain

Prof. Peter Carmeliet notes: “The neuronal stems cells that we discovered inside the meninges differentiate to full neurons, electrically-active and functionally integrated into the neuronal circuit. To show that the stem cells reside in the meninges, we used the extremely powerful single-cell RNA sequencing technique, a very novel top-notch technique, capable of identifying the [complex gene expression signature] nature of individual cells in a previously unsurpassed manner, a première at VIB.”

Following up on future research avenues

When it comes to future leads for this discovery, the scientists also see possibilities for translation into clinical application, though future work is required.

“An intriguing question is whether these neuronal stem cells in the meninges could lead to better therapies for brain damage or neurodegeneration. However, answering this question would require a better understanding of the molecular mechanisms that regulate the differentiation of these stem cells,” says Carmeliet. “How are these meningeal stem cells activated to become different kinds of neurons? Can we therapeutically ‘hijack’ their regeneration potential to restore dying neurons in, for example, Alzheimer’ Disease, Parkinson’s Disease, amyotrophic lateral sclerosis (ALS), and other neurodegenerative disorders? Also, can we isolate these neurogenic progenitors from the meninges at birth and use them for later transplantation? These findings open up very exciting research opportunities for the future.”

Moving into unchartered territory is high risk, and can offer high gain, but securing funding for such type of research is challenging. However, Carmeliet’s discoveries were made possible to a large extent by funding through “Opening the Future: pioneering without boundaries”, a recently created Mecenas Funding Campaign for funding of high risk brain research but with potential for breakthrough discoveries, started up by the KU Leuven in 2013 and unique in Flanders.

Read Next: A better way to grow motor neurons from stem cells

“Being able to use such non-conventional funding channels is of utmost importance to break new boundaries in research,” says Carmeliet. “This unique Mecenas funding initiative by the KU Leuven is innovative and boundary-breaking by itself. Our entire team is enormously grateful for the opportunities it has created for our investigations”.

Note: Material may have been edited for length and content. For further information, please contact the cited source.

VIB – Flanders Institute for Biotechnology   press release

Publication

Bifari F et al. Neurogenic Radial Glia-like Cells in Meninges Migrate and Differentiate into Functionally Integrated Neurons in the Neonatal Cortex.   Cell Stem Cell, Published Online November 23 2016. doi: 10.1016/j.stem.2016.10.020

Source: Scientists discover neuron-producing stem cells in the membranes covering the brain

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[WEB SITE] New hope for recovery of hand movement for stroke patients – Medical News Today

Published: Today

Stroke patients are starting a trial of a new electronic device to recover movement and control of their hand.

Neuroscientists at Newcastle University have developed the device, the size of a mobile phone, which delivers a series of small electrical shocks followed by an audible click to strengthen brain and spinal connections.

The experts believe this could revolutionise treatment for patients, providing a wearable solution to the effects of stroke.

Following successful work in primates and healthy human subjects, the Newcastle University team are now working with colleagues at the prestigious Institute of Neurosciences, Kolkata, India, to start the clinical trial. Involving 150 stroke patients, the aim of the study is to see whether it leads to improved hand and arm control.

Stuart Baker, Professor of Movement Neuroscience at Newcastle University who has led the work said: “We were astonished to find that a small electric shock and the sound of a click had the potential to change the brain’s connections. However, our previous research in primates changed our thinking about how we could activate these pathways, leading to our study in humans.”

Recovering hand control

Publishing in the Journal of Neuroscience, the team report on the development of the miniaturised device and its success in healthy patients at strengthening connections in the reticulospinal tract, one of the signal pathways between the brain and spinal cord.

This is important for patients as when people have a stroke they often lose the major pathway found in all mammals connecting the brain to spinal cord. The team’s previous work in primates showed that after a stroke they can adapt and use a different, more primitive pathway, the reticulospinal tract, to recover.

However, their recovery tends to be imbalanced with more connections made to flexors, the muscles that close the hand, than extensors, those that open the hand. This imbalance is also seen in stroke patients as typically, even after a period of recuperation, they find that they still have weakness of the extensor muscles preventing them opening their fist which leads to the distinctive curled hand.

Partial paralysis of the arms, typically on just one side, is common after stroke, and can affect someone’s ability to wash, dress or feed themselves. Only about 15% of stroke patients spontaneously recover the use of their hand and arm, with many people left facing the rest of their lives with a severe level of disability.

Senior author of the paper, Professor Baker added: “We have developed a miniaturised device which delivers an audible click followed by a weak electric shock to the arm muscle to strengthen the brain’s connections. This means the stroke patients in the trial are wearing an earpiece and a pad on the arm, each linked by wires to the device so that the click and shock can be continually delivered to them.

“We think that if they wear this for 4 hours a day we will be able to see a permanent improvement in their extensor muscle connections which will help them gain control on their hand.”

Improving connections

The techniques to strengthen brain connections using paired stimuli are well documented, but until now this has needed bulky equipment, with a mains electric supply.

The research published today is a proof of concept in human subjects and comes directly out of the team’s work on primates. In the paper they report how they pair a click in a headphone with an electric shock to a muscle to induce the changes in connections either strengthening or weakening reflexes depending on the sequence selected. They demonstrated that wearing the portable electronic device for seven hours strengthened the signal pathway in more than half of the subjects (15 out of 25).

Professor Stuart Baker added: “We would never have thought of using audible clicks unless we had the recordings from primates to show us that this might work. Furthermore, it is our earlier work in primates which shows that the connections we are changing are definitely involved in stroke recovery.”

The work has been funded through a Milstein Award from the Medical Research Council and the Wellcome Trust.

The clinical trial is just starting at the Institute of Neurosciences, Kolkata, India. The country has a higher rate of stroke than Western countries which can affect people at a younger age meaning there is a large number of patients. The Institute has strong collaborative links with Newcastle University enabling a carefully controlled clinical trial with results expected at the end of this year.

Article: Spike Timing-Dependent Plasticity in the Long-Latency Stretch Reflex Following Paired Stimulation from a Wearable Electronic Device, K. M. Riashad Foysal, Felipe de Carvalho and Stuart N. Baker, Journal of Neuroscience, doi: 10.1523/JNEUROSCI.1414-16.2016, published 19 October 2016.

Source: New hope for recovery of hand movement for stroke patients – Medical News Today

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