Neural Therapy Research Articles

Review of rehabilitation protocols for brachial plexus injury.

Brachial plexus injury (BPI) is one of the most serious peripheral nerve injuries, resulting in severe and persistent impairments of the upper limb and disability in adults and children alike. With the relatively mature early diagnosis and surgical technique of brachial plexus injury, the demand for rehabilitation treatment after brachial plexus injury is gradually increasing. Rehabilitation intervention can be beneficial to some extent during all stages of recovery, including the spontaneous recovery period, the postoperative period, and the sequelae period. However, due to the complex composition of the brachial plexus, location of injury, and the different causes, the treatment varies. A clear rehabilitation process has not been developed yet. Rehabilitation therapy that has been widely studied focusing on exercise therapy, sensory training, neuroelectromagnetic stimulation, neurotrophic factors, acupuncture and massage therapy, etc., while interventions like hydrotherapy, phototherapy, and neural stem cell therapy are less studied. In addition, rehabilitation methods in some special condition and group often neglected, such as postoperative edema, pain, and neonates. The purpose of this article is to explore the potential contributions of various methods to brachial plexus injury rehabilitation and to provide a concise overview of the interventions that have been shown to be beneficial. The key contribution of this article is to form relatively clear rehabilitation processes based on different periods and populations, which provides an important reference for the treatment of brachial plexus injuries.

Alzheimer’s Disease and Stem Cell Therapy

Alzheimer’s disease is a neurodegenerative disorder mainly caused by aggregation of neurofibrillary tangles and beta-amyloid plaques. As the most common cause of dementia, the population of AD patients has risen significantly in recent years. Due to the difficulty to diagnose AD at its early stage and the rapid development of the disease, AD is still an unsolved puzzle in the medical world. Though there are treatments for delaying symptoms of AD such as anti-amyloid therapy and medicine treatments that contain Cholinesterase inhibitors therapy, efficient therapies which treat AD fundamentally are yet to be discovered. The review paper will focus on one of the most promising therapies for AD, stem cell therapy. Compared to slowing down the disease, stem cell therapy can actually help the patients to grow brand-new neurons hence the treatment is pretty worthy to be studied. Stem cells are undifferentiated cells that are able to develop into new brain cells. There are four types of stem cell therapies for Alzheimer’s Disease: Mesenchymal Stem Cells therapy, Neural Stem Cell therapy, Embryonic Stem Cell therapy, and Induced Pluripotent stem Cell therapy. Among all the stem cell therapies, induced pluripotent stem cells (iPSC) therapy has the most potential to work out due to the successful trials upon rodent animal models. Nevertheless, no stem cell therapy for AD succeeds in human trials so far. Besides, the likelihood of cancer and tumor should also be taken into consideration.

Intra-body communications for nervous system applications: Current technologies and future directions

The Internet of Medical Things (IoMT) paradigm will enable next generation healthcare by enhancing human abilities, supporting continuous body monitoring and restoring lost physiological functions due to serious impairments. This paper presents intra-body communication solutions that interconnect implantable devices for application to the nervous system, challenging the specific features of the complex intra-body scenario. The presented approaches include both speculative and implementative methods, ranging from neural signal transmission to testbeds, to be applied to specific neural diseases therapies. Also future directions in this research area are considered to overcome the existing technical challenges mainly associated with miniaturization, power supply, and multi-scale communications.

Autonomic regulation therapy in chronic heart failure with preserved/mildly reduced ejection fraction: ANTHEM-HFpEF study results

BackgroundAutonomic regulation therapy (ART) utilizing cervical vagus nerve stimulation (VNS) appeared to be safe and to improve autonomic tone, symptoms, and cardiac mechanical function in patients with symptomatic heart failure and reduced ejection fraction in the ANTHEM-HF Study. The ANTHEM-HFpEF Study is the first investigation to evaluate the safety and feasibility of ART in patients with symptomatic heart failure and preserved or mildly reduced ejection fraction (HFpEF, HFmrEF). MethodsThis open-label interventional study enrolled 52 patients with HFpEF or HFmrEF, NYHA Class II-III, and LVEF ≥40%, who received stable guideline-directed medical therapy. All patients were successfully implanted with LivaNova VNS Therapy® system with an electrical lead surrounding the right cervical vagus nerve. ResultsAdverse event incidence was low. At 12 months, NYHA class (p <0.0001), 6-min walk distance (p <0.05), and quality of life (p <0.0001) were improved. Cardiac mechanical function measures were normal at baseline, except for left ventricular mass index in women and E/e' ratio in all patients, which were elevated at baseline, and were unchanged by ART. Autonomic tone and reflexes improved, indicated by 29% decrease in low-frequency/high-frequency heart rate variability to normal levels (p = 0.028) and by increased heart rate turbulence slope (p = 0.047). T-wave alternans (p = 0.001) and T-wave heterogeneity (p = 0.001) were reduced from abnormal to normal ranges. Nonsustained ventricular tachycardia incidence decreased (p = 0.027). ConclusionsART appeared well-tolerated and safe in patients with HFpEF or HFmrEF. Chronic ART did not alter mechanical function measures but was associated with improved heart failure symptoms, exercise tolerance, autonomic tone, and cardiac electrical stability. Clinical trial registryAutonomic Neural Regulation Therapy to Enhance Myocardial Function in Heart Failure with Preserved Ejection Fraction [ClinicalTrials.gov #NCT03163030, registered 05/22/2017].

Tanshinone IIA-loaded nanoparticles and neural stem cell combination therapy improves gut homeostasis and recovery in a pig ischemic stroke model

Impaired gut homeostasis is associated with stroke often presenting with leaky gut syndrome and increased gut, brain, and systemic inflammation that further exacerbates brain damage. We previously reported that intracisternal administration of Tanshinone IIA-loaded nanoparticles (Tan IIA-NPs) and transplantation of induced pluripotent stem cell-derived neural stem cells (iNSCs) led to enhanced neuroprotective and regenerative activity and improved recovery in a pig stroke model. We hypothesized that Tan IIA-NP + iNSC combination therapy-mediated stroke recovery may also have an impact on gut inflammation and integrity in the stroke pigs. Ischemic stroke was induced, and male Yucatan pigs received PBS + PBS (Control, n = 6) or Tan IIA-NP + iNSC (Treatment, n = 6) treatment. The Tan IIA-NP + iNSC treatment reduced expression of jejunal TNF-α, TNF-α receptor1, and phosphorylated IkBα while increasing the expression of jejunal occludin, claudin1, and ZO-1 at 12 weeks post-treatment (PT). Treated pigs had higher fecal short-chain fatty acid (SCFAs) levels than their counterparts throughout the study period, and fecal SCFAs levels were negatively correlated with jejunal inflammation. Interestingly, fecal SCFAs levels were also negatively correlated with brain lesion volume and midline shift at 12 weeks PT. Collectively, the anti-inflammatory and neuroregenerative treatment resulted in increased SCFAs levels, tight junction protein expression, and decreased inflammation in the gut.

Axon guidance gene-targeted siRNA delivery system improves neural stem cell transplantation therapy after spinal cord injury

BackgroundNeural stem cells (NSCs) derived from the embryonic spinal cord are excellent candidates for the cellular regeneration of lost neural cells after spinal cord injury (SCI). Semaphorin 3 A (Sema3A) is well known as being implicated in the major axon guidance of the growth cone as a repulsive function during the development of the central nervous system, yet its function in NSC transplantation therapy for SCI has not been investigated. Here, we report for the first time that embryonic spinal cord-derived NSCs significantly express Sema3A in the SCI environment, potentially facilitating inhibition of cell proliferation after transplantation.MethodssiRNA-Sema3A was conjugated with poly-l-lysin-coated gold nanoparticles (AuNPs) through a charge interaction process. NSCs were isolated from embryonic spinal cords of rats. Then, the cells were embedded into a dual-degradable hydrogel with the siRNA- Sema3A loaded-AuNPs and transplanted after complete SCI in rats.ResultsThe knockdown of Sema3A by delivering siRNA nanoparticles via dual-degradable hydrogels led to a significant increase in cell survival and neuronal differentiation of the transplanted NSCs after SCI. Of note, the knockdown of Sema3A increased the synaptic connectivity of transplanted NSC in the injured spinal cord. Moreover, extracellular matrix molecule and functional recovery were significantly improved in Sema3A-inhibited rats compared to those in rats with only NSCs transplanted.ConclusionsThese findings demonstrate the important role of Sema3A in NSC transplantation therapy, which may be considered as a future cell transplantation therapy for SCI cases.Graphical

Acceptability of neural stem cell therapy for cerebral palsy: survey of the Australian cerebral palsy community

BackgroundNeural stem cells (NSCs) have the potential to engraft and replace damaged brain tissue, repairing the damaged neonatal brain that causes cerebral palsy (CP). There are procedures that could increase engraftment of NSCs and may be critical for efficacy, but hold notable risks. Before clinical trials progress, it is important to engage with the CP community to understand their opinions. The aim of this study was to determine the acceptability of NSC therapy for CP in the CP community.MethodsAustralian residents with CP and parents/carers of those with CP completed a questionnaire to determine their willingness to use NSCs from three sources (fetal, embryonic and induced pluripotent stem cells) and their willingness to undergo accompanying procedures (neurosurgery, immunosuppression) that carry potential risks. To further explore their views, participants also answered free text questions about their ethical concerns regarding the source of NSCs and their perceptions of meaningful outcomes following NSC treatment.ResultsIn total, 232 responses were analyzed. Participants were willing to use NSCs from all three cell sources and were willing to undergo NSC therapy despite the need for neurosurgery and immunosuppression. Participants identified a range of outcome domains considered important following NSC treatment including gross motor function, quality of life, independence and cognitive function.ConclusionsHypothetical NSC therapy was acceptable to the Australian CP community. This study has identified important findings from the CP community which can be used to inform future NSC research, including the design of clinical trials which may help to increase recruitment, compliance and participant satisfaction.

Developing an iPSC-based neural gene therapy approach for MPS IIIA

Developing an iPSC-based neural gene therapy approach for MPS IIIA

Treatment of Carpal Tunnel Syndrome with Neural Therapy: A Case Report

Treatment of Carpal Tunnel Syndrome with Neural Therapy: A Case Report

Treatment of Lateral Epicondylitis with Neural Therapy: A Case Report

Treatment of Lateral Epicondylitis with Neural Therapy: A Case Report

Neural Therapy in the Treatment of Painful Ganglion Cyst: A Case Report

Neural Therapy in the Treatment of Painful Ganglion Cyst: A Case Report

A Narrative Review of Advances in Neural Precursor Cell Transplantation Therapies for Spinal Cord Injury.

A spinal cord injury (SCI) is a destructive event that causes a permanent deficit in neurological function because of poor regenerative potential. Transplantation therapies have attracted attention for restoration of the injured spinal cord, and transplantation of neural precursor cells (NPCs) has been studied worldwide. Several groups have demonstrated functional recovery via this therapeutic intervention due to the multiple beneficial effects of NPC transplantation, such as reconstruction of neuronal circuits, remyelination of axons, and neuroprotection by trophic factors. Our group developed a method to induce NPCs from human induced pluripotent stem cells (hiPSCs) and established a transplantation strategy for SCI. Functional improvement in SCI animals treated with hiPSC-NPCs was observed, and the safety of transplanting these cells was evaluated from multiple perspectives. With selection of a safe cell line and pretreatment of the cells to encourage maturation and differentiation, hiPSC-NPC transplantation therapy is now in the clinical phase of testing for subacute SCI. In addition, a research challenge will be to expand the efficacy of transplantation therapy for chronic SCI. More comprehensive strategies involving combination treatments are required to treat this problematic situation.

Nöral Terapinin Servikal Diskopatiye Bağlı Kronik Boyun Ağrısına Etkisi

Introduction: To investigate how 1% procaine injection therapy, one of the neural therapeutic agents, affects neck disability and pain intensity in patients who have cervical discopathies that are causing chronic neck pain and/or functional limitations Methods: The records of 58 patients diagnosed with cervical discopathy were examined. The Range of Motion values, Neck Disability Questionnaire and Visual Analog Scale scores were compared at baseline and one month after neural therapy. The results of cervical magnetic resonance imaging were analyzed, and the mean scores were compared between the protrusion and bulging. P values of &amp;lt;0.05 were considered statistically significant. Results: A statistically significant increase was observed in Range of Motion values after NT in all movements of the neck and the decrease in the mean Visual Analog Scale and Neck Disability Index scores after neural therapy were found to be statistically significant in both the protrusion and bulging groups. Conclusion: This is the first study providing evidence of the effects of neural therapy on neck pain severity and neck disability in adult patients with cervical discopathies (protrusion and bulging) presenting with chronic neck pain resistant to medical treatment, who had not yet made a surgical decision.

Laser-Structured Si and PLGA Inhibit the Neuro2a Differentiation in Mono- and Co-Culture with Glia

Background:The first step towards a successful neural tissue engineering therapy is the development of an appropriate scaffold and the in vitro study of the cellular response onto it.Methods:Here, we fabricated nano- and micro- patterned Si surfaces via direct ultrafast laser irradiation, as well as their replicas in the biodegradable poly(lactide-co-glycolide), in order to use them as culture substrates for neuronal cells. The differentiation of neuro2a cells on the Si platforms and their replicas was studied both in a mono-culture and in a co-culture with glial cells (Schwann—SW10).Results:It was found that the substrate’s roughness inhibits the differentiation of the neuronal cells even in the presence of the differentiation medium, and the higher the roughness is, the more the differentiation gets limited.Conclusion:Our results highlight the importance of the substrate’s topography for the controlled growth and differentiation of the neuronal cells and their further study via protein screening methods could shed light on the factors that lead to limited differentiation; thus, contributing to the long standing request for culture substrates that induce cells to differentiate.

Combined Effect of Constraint Induced Movement Therapy and Neural Mobilization Technique on Upper Extremity Function in Spastic Hemiplegic Patient – A Single Case Study

Purpose: A single case study was performed carried to understand the benefit of constraint movement therapy and neural mobilization technique and neural mobilization technique on upper extremity function in spastic hemiplegic patient. Design/Methodology/Approach: Numerous advanced researches have been done throughout the world in various study designs including systematic reviews and randomized control trials to analyse the significance of constraint induced movement therapy or neural mobilization technique on upper extremity function spastic hemiplegic patients. But there were very limited research publications on the combined effect of both in the improvement of upper extremity function. In this single case study combined intervention of constrained induced movement therapy and neural mobilization therapy was given to the patient to measure the effect in the form of functional arm reach distance of affected upper extremity. Data was recorded, kept for analysis and reported. The respondent of this single case study was patient encountered with left side hemiplegia with spastic upper extremity. Finding/Result: This case study shown significant improvement in the outcome of modified ashworth scale grades and upper extremity functional arm reach distance in spastic hemiplegic patient after intervention of combined movement of constrained induced movement therapy with neural mobilization for 24 weeks. Originality/Value: Constrained Induced Movement Therapy for improving hand functions in stroke treatment. Paper Type: Case Study Research

Transcription Factor-Mediated Differentiation of Motor Neurons from Human Pluripotent Stem Cells.

Studying the pathogenesis of neurological diseases with animal models might not always truly recapitulate their pathophysiology, due to species differences. Fortunately, human pluripotent stem cells (hPSCs) including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), especially derived from patients, have been widely employed to induce neural progenitor cells (NPCs) and further multiple neural subtypes. Particularly in the past decade, hPSC-based cell sources have been applied in studying neural development, cell therapy, disease modeling, and drug screening, among others. The generation of unlimited amount of neurons also facilitates a variety of biochemical assays, mass spectrometry, omic analysis, and next-generation sequencing, which thus provides an excellent tool in modeling neurodegenerative and neurodevelopmental diseases. Dysfunction or death of motor neurons (MNs) in the spinal cord and motor cortex is implicated in various motor neuron diseases (MNDs). Yet, producing high-purity and high-yield MNs remains a major challenge due to the complexity of MN specification during development. In this chapter, we describe a method of generating functional MNs via lentiviral delivery of transcription factors, based on the preservable NPC platform derived from hPSCs. Specifically, we transduce NPCs with a single lentivirus co-expressing three transcription factors including NGN2, ISL1, and LHX3, which is necessary and sufficient to induce mature MNs with high efficiencies (~90%) within 3weeks. This chapter thus provides a robust method to generate high-purity hPSC-MNs at very high yields, enabling the acquisition of rich patient-specific MNs to be used for modeling the molecular underpinnings of MNDs.

Advances in Neural Stem Cell Therapy for Spinal Cord Injury: Safety, Efficacy, and Future Perspectives.

Spinal cord injury (SCI) is a devastating central nervous system injury that leads to severe disabilities in motor and sensory functions, causing significant deterioration in patients' quality of life. Owing to the complexity of SCI pathophysiology, there has been no effective treatment for reversing neural tissue damage and recovering neurological functions. Several novel therapies targeting different stages of pathophysiological mechanisms of SCI have been developed. Among these, treatments using stem cells have great potential for the regeneration of damaged neural tissues. In this review, we have summarized recent preclinical and clinical studies focusing on neural stem cells (NSCs). NSCs are multipotent cells with specific differentiation capabilities for neural lineage. Several preclinical studies have demonstrated the regenerative effects of transplanted NSCs in SCI animal models through both paracrine effects and direct neuronal differentiation, restoring synaptic connectivity and neural networks. Based on the positive results of several preclinical studies, phase I and II clinical trials using NSCs have been performed. Despite several hurdles and issues that need to be addressed in the clinical use of NSCs in patients with SCI, gradual progress in the technical development and therapeutic efficacy of NSCs treatments has enhanced the prospects for cell-based treatments in SCI.

O054 Genioglossus neural drive and upper airway dilation in people with obstructive sleep apnoea during wakefulness

Abstract Introduction Genioglossus neural drive and the ensuing tongue dilatory movement may be dissociated in obstructive sleep apnoea (OSA), but this has not been studied. This study aimed to investigate this relationship and its potential role in OSA pathophysiology. Methods During awake nasal breathing in the supine position, inspiratory tongue dilatory movement, quantified with tagged magnetic resonance imaging, and inspiratory peak genioglossus electromyography (EMG) normalised to the maximum voluntary contraction (tongue protrusion), were measured in 4 tongue neuromuscular compartments from 8 controls [apnea-hypopnea index (AHI)&amp;lt;5 events/h] and 34 patients with untreated OSA [AHI&amp;gt;10 events/h]. Results Although larger inspiratory dilatory movement was associated with increased drive to genioglossus (partial Spearman, r=0.23, p=0.016, n=115/68% of compartments), in 14% of the compartments (n=16), there was a large dilatory (&amp;gt;1mm) movement but minimal EMG (&amp;lt;4th percentile). This occurred only in the horizontal compartment. In another group of 18 compartments (16%), there was a large peak EMG (&amp;gt;4th percentile) but minimal dilatory movement (&amp;lt;1mm). This occurred more commonly in the oblique compartments. Dissociation between the amplitude of the peak EMG and inspiratory tongue dilatory movement was most commonly seen in severe OSA patients (AHI&amp;gt;30 events/h, Fisher's exact test, p=0.047). Conclusions Inspiratory tongue dilatory function generally remains closely linked to muscle drive during wakefulness, with larger movement associated with higher peak EMG. However, for approximately one-third of the neuromuscular tongue compartments, neural drive was dissociated from the dilatory motion in severe OSA patients. This may contribute to OSA pathogenesis and have implications for neural stimulation therapy targets.

Transplanting neurofibromatosis-1 gene knockout neural stem cells improve functional recovery in rats with spinal cord injury by enhancing the mTORC2 pathway

The poor survival and low efficiency of neuronal differentiation limits the therapeutic effects of transplanted neural stem cells in the treatment of spinal cord injury. Neurofibromatosis-1 (NF-1) is a tumor suppressor gene that restricts the rapid and abnormal growth and differentiation of neural cells. In the present study, lentiviral vectors were used to knock out NF-1, Ricotr (the core member of mTORC2) or NF-1+Ricotr in neural stem cells in vitro, and the NF-1, Ricotr or NF-1+Ricotr knockout neural stem cells were transplanted at the lesion site in a rat model of spinal cord injury (SCI). We first demonstrated that targeted knockout of NF-1 had an antiapoptotic effect and improved neuronal differentiation by enhancing the mTORC2/Rictor pathway of neural stem cells in vitro. Subsequently, transplanting NF-1 knockout neural stem cells into the injured site sufficiently promoted the tissue repair and functional recovery of rats with spinal cord injury by enhancing the survival and neuronal differentiation of grafted neural stem cells. Collectively, these findings reveal a prominent role of NF-1 in neural stem cell biology, which is an invaluable step forward in enhancing the benefit of neural stem cell-mediated regenerative cell therapy for spinal cord injury and identifies the transplantation of NF-1 knockout neural stem cells as a promising strategy for spinal cord injury.

Tanshinone IIA-Loaded Nanoparticle and Neural Stem Cell Therapy Enhances Recovery in a Pig Ischemic Stroke Model.

Induced pluripotent stem cell-derived neural stem cells (iNSCs) are a multimodal stroke therapeutic that possess neuroprotective, regenerative, and cell replacement capabilities post-ischemia. However, long-term engraftment and efficacy of iNSCs is limited by the cytotoxic microenvironment post-stroke. Tanshinone IIA (Tan IIA) is a therapeutic that demonstrates anti-inflammatory and antioxidative effects in rodent ischemic stroke models and stroke patients. Therefore, pretreatment with Tan IIA may create a microenvironment that is more conducive to the long-term survival of iNSCs. In this study, we evaluated the potential of Tan IIA drug-loaded nanoparticles (Tan IIA-NPs) to improve iNSC engraftment and efficacy, thus potentially leading to enhanced cellular, tissue, and functional recovery in a translational pig ischemic stroke model. Twenty-two pigs underwent middle cerebral artery occlusion (MCAO) and were randomly assigned to a PBS + PBS, PBS + iNSC, or Tan IIA-NP + iNSC treatment group. Magnetic resonance imaging (MRI), modified Rankin Scale neurological evaluation, and immunohistochemistry were performed over a 12-week study period. Immunohistochemistry indicated pretreatment with Tan IIA-NPs increased iNSC survivability. Furthermore, Tan IIA-NPs increased iNSC neuronal differentiation and decreased iNSC reactive astrocyte differentiation. Tan IIA-NP + iNSC treatment enhanced endogenous neuroprotective and regenerative activities by decreasing the intracerebral cellular immune response, preserving endogenous neurons, and increasing neuroblast formation. MRI assessments revealed Tan IIA-NP + iNSC treatment reduced lesion volumes and midline shift. Tissue preservation and recovery corresponded with significant improvements in neurological recovery. This study demonstrated pretreatment with Tan IIA-NPs increased iNSC engraftment, enhanced cellular and tissue recovery, and improved neurological function in a translational pig stroke model.