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1.
Dis Model Mech ; 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34746950

RESUMO

Fundamental questions about patient heterogeneity and human-specific pathophysiology currently obstruct progress towards a therapy for traumatic brain injury (TBI). Human in vitro models have the potential to address these questions. 3D spheroidal cell culture protocols for human-origin neural cells have several important advantages over their 2D monolayer counterparts. Three dimensional spheroidal cultures may mature more quickly, develop more biofidelic electrophysiological activity and/or reproduce some aspects of brain architecture. Here, we present the first human in vitro model of non-penetrating TBI employing 3D spheroidal cultures. We used a custom-built device to traumatize these spheroids in a quantifiable, repeatable and biofidelic manner and correlated the heterogeneous, mechanical strain field with the injury phenotype. Trauma reduced cell viability, mitochondrial membrane potential and spontaneous, synchronous, electrophysiological activity in the spheroids. Electrophysiological deficits emerged at lower injury severities than changes in cell viability. Also, traumatized spheroids secreted lactate dehydrogenase, a marker of cell damage, and neurofilament light chain, a promising clinical biomarker of neurotrauma. These results demonstrate that 3D human in vitro models can reproduce important phenotypes of neurotrauma in vitro.

2.
J Vis Exp ; (176)2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34747395

RESUMO

Peripheral nerve interfaces are frequently used in experimental neuroscience and regenerative medicine for a wide variety of applications. Such interfaces can be sensors, actuators, or both. Traditional methods of peripheral nerve interfacing must either tether to an external system or rely on battery power that limits the time frame for operation. With recent developments of wireless, battery-free, and fully implantable peripheral nerve interfaces, a new class of devices can offer capabilities that match or exceed those of their wired or battery-powered precursors. This paper describes methods to (i) surgically implant and (ii) wirelessly power and control this system in adult rats. The sciatic and phrenic nerve models were selected as examples to highlight the versatility of this approach. The paper shows how the peripheral nerve interface can evoke compound muscle action potentials (CMAPs), deliver a therapeutic electrical stimulation protocol, and incorporate a conduit for the repair of peripheral nerve injury. Such devices offer expanded treatment options for single-dose or repeated dose therapeutic stimulation and can be adapted to a variety of nerve locations.

3.
J Electromyogr Kinesiol ; 60: 102573, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34273729

RESUMO

INTRODUCTION: Anatomic landmarks alone may not always be sufficient to accurately guide electromyography (EMG) electrode needle placement. METHODS: Senior residents and fellows (n = 11) targeted 4 forearm muscles with anatomic landmarks alone versus with audiovisual EMG feedback. Accuracy of EMG needle placement was verified using neuromuscular ultrasound imaging. RESULTS: While relatively large and superficial FCR muscle was sampled at a rate of 100% with and without audiovisual EMG feedback, accuracy of deeper and/or smaller forearm muscles (FPL, EIP, and SUP) diminished significantly without audiovisual EMG feedback. DISCUSSION: Our study suggests that in clinical scenarios in which an electrodiagnostician relies on anatomic landmarks alone to target small and deep muscles, the risk of misplacement of needle electrode is increased. Consideration for neuromuscular ultrasound to augment training and/or real time guidance in EMG practice may be appropriate.


Assuntos
Antebraço , Músculo Esquelético , Eletrodos , Eletromiografia , Antebraço/diagnóstico por imagem , Humanos , Músculo Esquelético/diagnóstico por imagem , Ultrassonografia
4.
Ann Clin Transl Neurol ; 8(8): 1745-1749, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34247452

RESUMO

Many survivors from severe coronavirus disease 2019 (COVID-19) suffer from persistent dyspnea and fatigue long after resolution of the active infection. In a cohort of 21 consecutive severe post-COVID-19 survivors admitted to an inpatient rehabilitation hospital, 16 (76%) of them had at least one sonographic abnormality of diaphragm muscle structure or function. This corresponded to a significant reduction in diaphragm muscle contractility as represented by thickening ratio (muscle thickness at maximal inspiration/end-expiration) for the post-COVID-19 compared to non-COVID-19 cohorts. These findings may shed new light on neuromuscular respiratory dysfunction as a contributor to prolonged functional impairments after hospitalization for post-COVID-19.


Assuntos
COVID-19/complicações , Diafragma , Ultrassonografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico por imagem , COVID-19/patologia , COVID-19/fisiopatologia , Diafragma/diagnóstico por imagem , Diafragma/patologia , Diafragma/fisiopatologia , Feminino , Hospitais de Reabilitação , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade
5.
Sci Adv ; 7(12)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33731359

RESUMO

Three-dimensional (3D), submillimeter-scale constructs of neural cells, known as cortical spheroids, are of rapidly growing importance in biological research because these systems reproduce complex features of the brain in vitro. Despite their great potential for studies of neurodevelopment and neurological disease modeling, 3D living objects cannot be studied easily using conventional approaches to neuromodulation, sensing, and manipulation. Here, we introduce classes of microfabricated 3D frameworks as compliant, multifunctional neural interfaces to spheroids and to assembloids. Electrical, optical, chemical, and thermal interfaces to cortical spheroids demonstrate some of the capabilities. Complex architectures and high-resolution features highlight the design versatility. Detailed studies of the spreading of coordinated bursting events across the surface of an isolated cortical spheroid and of the cascade of processes associated with formation and regrowth of bridging tissues across a pair of such spheroids represent two of the many opportunities in basic neuroscience research enabled by these platforms.

6.
J Ultrasound Med ; 2021 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-33772850

RESUMO

The diaphragm, the principle muscle of inspiration, is an under-recognized contributor to respiratory disease. Dysfunction of the diaphragm can occur secondary to lung disease, prolonged ventilation, phrenic nerve injury, neuromuscular disease, and central nervous system pathology. In light of the global pandemic of coronavirus disease 2019 (COVID-19), there has been growing interest in the utility of ultrasound for evaluation of respiratory symptoms including lung and diaphragm sonography. Diaphragm ultrasound can be utilized to diagnose diaphragm dysfunction, assess severity of dysfunction, and monitor disease progression. This article reviews diaphragm and phrenic nerve ultrasound and describes clinical applications in the context of COVID-19.

7.
Skeletal Radiol ; 50(9): 1763-1773, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33598718

RESUMO

The global pandemic of coronavirus disease 2019 (COVID-19) has revealed a surprising number of extra-pulmonary manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. While myalgia is a common clinical feature of COVID-19, other musculoskeletal manifestations of COVID-19 were infrequently described early during the pandemic. There have been emerging reports, however, of an array of neuromuscular and rheumatologic complications related to COVID-19 infection and disease course including myositis, neuropathy, arthropathy, and soft tissue abnormalities. Multimodality imaging supports diagnosis and evaluation of musculoskeletal disorders in COVID-19 patients. This article aims to provide a first comprehensive summary of musculoskeletal manifestations of COVID-19 with review of imaging.


Assuntos
COVID-19 , Doenças do Sistema Nervoso Periférico , Humanos , Pulmão , Pandemias , SARS-CoV-2
9.
Radiology ; 298(3): E117-E130, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33258748

RESUMO

With surging numbers of patients with coronavirus disease 2019 (COVID-19) throughout the world, neuromuscular complications and rehabilitation concerns are becoming more apparent. Peripheral nerve injury can occur in patients with COVID-19 secondary to postinfectious inflammatory neuropathy, prone positioning-related stretch and/or compression injury, systemic neuropathy, or nerve entrapment from hematoma. Imaging of peripheral nerves in patients with COVID-19 may help to characterize nerve abnormality, to identify site and severity of nerve damage, and to potentially elucidate mechanisms of injury, thereby aiding the medical diagnosis and decision-making process. This review article aims to provide a first comprehensive summary of the current knowledge of COVID-19 and peripheral nerve imaging.


Assuntos
COVID-19/complicações , Diagnóstico por Imagem/métodos , Traumatismos dos Nervos Periféricos/complicações , Traumatismos dos Nervos Periféricos/diagnóstico por imagem , Diagnóstico Diferencial , Humanos , Posicionamento do Paciente/métodos , Nervos Periféricos/diagnóstico por imagem , SARS-CoV-2
10.
Sleep Med Clin ; 15(4): 539-543, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33131663

RESUMO

Neuralgic amyotrophy is a poorly understood neuromuscular disorder affecting peripheral nerves mostly within the brachial plexus distribution but can also involve other sites including the phrenic nerve. In the classic form of the syndrome it causes proximal upper limb and neck pain on the affected side with subsequent muscle weakness that can be highly heterogeneous. Nocturnal noninvasive ventilation support is a first-line treatment after phrenic mononeuropathy. The regular monitoring of diaphragm function with spirometry and diaphragm ultrasound can help determine prognosis and inform decision-making.


Assuntos
Neurite do Plexo Braquial , Diafragma/diagnóstico por imagem , Ventilação não Invasiva , Nervo Frênico , Neurite do Plexo Braquial/fisiopatologia , Neurite do Plexo Braquial/terapia , Humanos , Nervo Frênico/fisiopatologia
11.
Nat Commun ; 11(1): 5990, 2020 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-33239608

RESUMO

Bioresorbable electronic stimulators are of rapidly growing interest as unusual therapeutic platforms, i.e., bioelectronic medicines, for treating disease states, accelerating wound healing processes and eliminating infections. Here, we present advanced materials that support operation in these systems over clinically relevant timeframes, ultimately bioresorbing harmlessly to benign products without residues, to eliminate the need for surgical extraction. Our findings overcome key challenges of bioresorbable electronic devices by realizing lifetimes that match clinical needs. The devices exploit a bioresorbable dynamic covalent polymer that facilitates tight bonding to itself and other surfaces, as a soft, elastic substrate and encapsulation coating for wireless electronic components. We describe the underlying features and chemical design considerations for this polymer, and the biocompatibility of its constituent materials. In devices with optimized, wireless designs, these polymers enable stable, long-lived operation as distal stimulators in a rat model of peripheral nerve injuries, thereby demonstrating the potential of programmable long-term electrical stimulation for maintaining muscle receptivity and enhancing functional recovery.


Assuntos
Implantes Absorvíveis , Terapia por Estimulação Elétrica/instrumentação , Traumatismos dos Nervos Periféricos/terapia , Poliuretanos/química , Tecnologia sem Fio/instrumentação , Animais , Modelos Animais de Doenças , Terapia por Estimulação Elétrica/métodos , Feminino , Humanos , Teste de Materiais , Músculo Esquelético/inervação , Músculo Esquelético/fisiologia , Ratos , Regeneração , Nervo Isquiático/lesões , Nervo Isquiático/fisiologia
12.
Sci Adv ; 6(35): eabb1093, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32923633

RESUMO

Implantable drug release platforms that offer wirelessly programmable control over pharmacokinetics have potential in advanced treatment protocols for hormone imbalances, malignant cancers, diabetic conditions, and others. We present a system with this type of functionality in which the constituent materials undergo complete bioresorption to eliminate device load from the patient after completing the final stage of the release process. Here, bioresorbable polyanhydride reservoirs store drugs in defined reservoirs without leakage until wirelessly triggered valve structures open to allow release. These valves operate through an electrochemical mechanism of geometrically accelerated corrosion induced by passage of electrical current from a wireless, bioresorbable power-harvesting unit. Evaluations in cell cultures demonstrate the efficacy of this technology for the treatment of cancerous tissues by release of the drug doxorubicin. Complete in vivo studies of platforms with multiple, independently controlled release events in live-animal models illustrate capabilities for control of blood glucose levels by timed delivery of insulin.

14.
Neurol Clin ; 38(3): 565-575, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32703469

RESUMO

Amyotrophic lateral sclerosis (ALS) is a fatal disease with no cure; however, symptomatic management has an impact on quality of life and survival. Symptom management is best performed in a multidisciplinary care setting, where patients are evaluated by multiple health care professionals. Respiratory failure is a significant cause of morbidity and mortality in patients with ALS. Early initiation of noninvasive ventilation can prolong survival, and adequate use of airway clearance techniques can prevent respiratory infections. Preventing and treating weight loss caused by dysphagia may slow down disease progression, and expert management of spasticity from upper motor neuron dysfunction enhances patient well-being.


Assuntos
Esclerose Amiotrófica Lateral/fisiopatologia , Esclerose Amiotrófica Lateral/terapia , Gerenciamento Clínico , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/terapia , Adulto , Esclerose Amiotrófica Lateral/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Insuficiência Respiratória/etiologia
15.
Muscle Nerve ; 61(5): 616-622, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32086830

RESUMO

INTRODUCTION: Evaluation of nerve mechanical properties has the potential to improve assessment of nerve impairment. Shear wave velocity, as measured by using shear wave (SW) ultrasound elastography, is a promising indicator of nerve mechanical properties such as stiffness. However, elucidation of external factors that influence SW velocity, particularly nerve tension, is required for accurate interpretations. METHODS: Median and ulnar nerve SW velocities were measured at proximal and distal locations with limb positions that indirectly altered nerve tension. RESULTS: Shear wave velocity was greater at proximal and distal locations for limb positions that induced greater tension in the median (mean increase proximal 89.3%, distal 64%) and ulnar (mean increase proximal 91.1%, distal 37.4%) nerves. DISCUSSION: Due to the influence of nerve tension when SW ultrasound elastography is used, careful consideration must be given to limb positioning.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Nervo Mediano/diagnóstico por imagem , Postura , Nervo Ulnar/diagnóstico por imagem , Extremidade Superior , Adolescente , Adulto , Fenômenos Biomecânicos , Feminino , Voluntários Saudáveis , Humanos , Masculino , Nervo Mediano/anatomia & histologia , Nervo Mediano/fisiologia , Tamanho do Órgão , Nervo Ulnar/anatomia & histologia , Nervo Ulnar/fisiologia , Ultrassonografia/métodos , Adulto Jovem
16.
J Neurophysiol ; 122(3): 1174-1185, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31116639

RESUMO

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of upper and lower motor neurons, which manifests clinically as progressive weakness. Although several epidemiological studies have found an association between traumatic brain injury (TBI) and ALS, there is not a consensus on whether TBI is an ALS risk factor. It may be that it can cause ALS in a subset of susceptible patients, based on a history of repetitive mild TBI and genetic predisposition. This cannot be determined based on clinical observational studies alone. Better preclinical models are necessary to evaluate the effects of TBI on ALS onset and progression. To date, only a small number of preclinical studies have been performed, mainly in the superoxide dismutase 1 transgenic rodents, which, taken together, have mixed results and notable methodological limitations. The more recent incorporation of additional animal models such as Drosophila flies, as well as patient-induced pluripotent stem cell-derived neurons, should facilitate a better understanding of a potential functional interaction between TBI and ALS.


Assuntos
Esclerose Amiotrófica Lateral , Concussão Encefálica , Proteínas de Ligação a DNA , Células-Tronco Pluripotentes Induzidas , Superóxido Dismutase-1 , Esclerose Amiotrófica Lateral/etiologia , Esclerose Amiotrófica Lateral/metabolismo , Esclerose Amiotrófica Lateral/fisiopatologia , Animais , Concussão Encefálica/complicações , Concussão Encefálica/metabolismo , Concussão Encefálica/fisiopatologia , Humanos
17.
Neurorehabil Neural Repair ; 32(8): 735-745, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30043670

RESUMO

BACKGROUND: Peripheral axon regeneration is improved when the nerve lesion under consideration has recently been preceded by another nerve injury. This is known as the conditioning lesion effect (CLE). While the CLE is one of the most robust and well characterized means to enhance motor axon regeneration in experimental models, it is not considered a clinically feasible strategy. A pharmacological means to re-produce the CLE is highly desirable. OBJECTIVE: To test whether chemodenervation with a clinical grade formulation of botulinum toxin A (BoTX) would be sufficient to reproduce the CLE. METHODS: We examined the effects of a 1-week preconditioning administration of BoTX on motor axon regrowth in both a mouse tibial nerve injury and human embryonic stem cell (hESC)-based model. We assessed neuronal reinnervation in vivo (mice) with retrograde tracers and histological analysis of peripheral nerve tissue after injections into the triceps surae muscle group. We assessed motor neuron neurite outgrowth in vitro (hESC) after incubation in BoTX by immunohistochemistry and morphometric analysis. RESULTS: We found that BoTX conditioning treatment significantly enhanced outgrowth of both murine motor axons in vivo and human MN neurites in vitro. CONCLUSIONS: BoTX preconditioning represents a pharmacological candidate approach to enhance motor axon regeneration in specific clinical scenarios such as nerve transfer surgery. Further studies are needed to elucidate the molecular mechanism.


Assuntos
Axônios/efeitos dos fármacos , Toxinas Botulínicas/farmacologia , Neurônios Motores/efeitos dos fármacos , Regeneração Nervosa/efeitos dos fármacos , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Animais , Axônios/fisiologia , Toxinas Botulínicas/uso terapêutico , Células-Tronco Embrionárias , Humanos , Masculino , Camundongos , Neurônios Motores/fisiologia , Regeneração Nervosa/fisiologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Nervo Tibial/efeitos dos fármacos , Nervo Tibial/lesões , Nervo Tibial/fisiopatologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-29951280

RESUMO

Introduction: People with spinal cord injury (SCI) are getting older due to a combination of increased life expectancy and older age at the time of injury. This trend makes it more likely for these patients to have other chronic health conditions including cancer. Inevitably relatively rare cancers such as soft tissue sarcomas (STS), which are more common with advancing age, will occur in some SCI patients. The present case represents the first report of a limb STS in a patient with chronic paraplegia from a traumatic SCI. Case presentation: We report a case of a 50-year-old right handed male with a T6 chronic, complete SCI (American Spinal Injury Association Impairment Scale A) who presented with a large mass involving his right shoulder musculature that was determined to be a high grade spindle cell sarcoma. The patient was followed closely by Physiatry over an approximately 6-month time course including prior to his tumor diagnosis, during the pre-radiation and pre-surgical planning phase, and then post-operatively for his acute inpatient rehabilitation. He was successfully discharged home to live alone in his accessible apartment complex. Discussion: This case is the first ever reported case of a person living with a traumatic SCI who subsequently developed a limb STS. In addition to its novelty, this case illustrates how health conditions such as rare cancers are presenting more often as the chronic SCI population is getting older, which creates both unique diagnostic and management challenges for cancer rehabilitation specialists.

19.
World Neurosurg ; 85: 325-32, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26409073

RESUMO

Brachial plexus trauma (BPT) often affects young patients and may result in lasting functional deficits. Standard care following BPT involves monitoring for clinical and electrophysiological evidence of muscle reinnervation, with surgical treatment decisions based on the presence or absence of spontaneous recovery. Data are emerging to suggest that central and peripheral adaptation may play a role in recovery following BPT. The present review highlights adaptive and maladaptive mechanisms of central and peripheral nervous system changes following BPT that may contribute to functional outcomes. Rehabilitation and other treatment strategies that harness or modulate these intrinsic adaptive mechanisms may improve functional outcomes following BPT.


Assuntos
Adaptação Fisiológica/fisiologia , Braço/inervação , Plexo Braquial/lesões , Plexo Braquial/fisiopatologia , Encéfalo/fisiopatologia , Músculo Esquelético/inervação , Regeneração Nervosa/fisiologia , Adulto , Apraxias/fisiopatologia , Traumatismos do Nascimento/diagnóstico , Traumatismos do Nascimento/fisiopatologia , Traumatismos do Nascimento/reabilitação , Traumatismos do Nascimento/cirurgia , Plexo Braquial/cirurgia , Neuropatias do Plexo Braquial/fisiopatologia , Neuropatias do Plexo Braquial/cirurgia , Terapia Combinada , Eletromiografia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Estimulação Elétrica Nervosa Transcutânea
20.
Neurosurgery ; 72(4): 653-61; discussion 661, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23277370

RESUMO

BACKGROUND: Neuromodulation is used to restore neural function in disorders that stem from an imbalance in the activity of specific neural networks when they prove refractory to pharmacological therapy. The Kir2.1 gene contributes to stabilizing the resting potential below the threshold of activation of voltage-gated sodium channels and action potentials. Therefore, the delivery of the Kir2.1 gene to neuronal cells could reduce the probability of action potential generation, inhibiting excessive neural activity. OBJECTIVE: To address the hypothesis that overexpression of the inwardly rectifying potassium channel 2.1 (Kir2.1) gene could inhibit motor neuron activity and therefore be therapeutically used in gene-based neuromodulation. METHODS: To induce expression of Kir2.1, the inducible RheoSwitch promoter was used and controlled by ligand. In vivo gene expression was accomplished by an adenoviral vector to deliver unilaterally into the lumbar spinal cord of rats. RESULTS: Behavioral assays demonstrated that neuromuscular inhibition was exclusive to rats that received the ligand. Histological analysis also showed evidence of some motor neuron loss in these animals. Behavioral effects of Kir2.1 expression were completely reversible, arguing that the behavioral effect did not result from motor neuron death. CONCLUSION: Delivery of the gene for Kir2.1 inhibits neurons by resisting depolarization to the action potential threshold. Regulated neuronal expression of Kir2.1 may provide an elegant means for neuromodulation in a selected neuronal population.


Assuntos
Regulação da Expressão Gênica , Técnicas de Transferência de Genes , Neurônios/fisiologia , Canais de Potássio Corretores do Fluxo de Internalização/biossíntese , Medula Espinal/fisiologia , Animais , Linhagem Celular Tumoral , Regulação da Expressão Gênica/fisiologia , Humanos , Fármacos Neuromusculares Despolarizantes/farmacologia , Canais de Potássio Corretores do Fluxo de Internalização/genética , Canais de Potássio Corretores do Fluxo de Internalização/fisiologia , Distribuição Aleatória , Ratos , Medula Espinal/citologia
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