RESUMEN
Cerebrospinal fluid (CSF) is responsible for maintaining brain homeostasis through nutrient delivery and waste removal for the central nervous system (CNS). Here, we demonstrate extensive CSF flow throughout the peripheral nervous system (PNS) by tracing distribution of multimodal 1.9-nanometer gold nanoparticles, roughly the size of CSF circulating proteins, infused within the lateral cerebral ventricle (a primary site of CSF production). CSF-infused 1.9-nanometer gold transitions from CNS to PNS at root attachment/transition zones and distributes through the perineurium and endoneurium, with ultimate delivery to axoplasm of distal peripheral nerves. Larger 15-nanometer gold fails to transit from CNS to PNS and instead forms "dye-cuffs," as predicted by current dogma of CSF restriction within CNS, identifying size limitations in central to peripheral flow. Intravenous 1.9-nanometer gold is unable to cross the blood-brain/nerve barrier. Our findings suggest that CSF plays a consistent role in maintaining homeostasis throughout the nervous system with implications for CNS and PNS therapy and neural drug delivery.
Asunto(s)
Líquido Cefalorraquídeo , Nervios Periféricos , Animales , Líquido Cefalorraquídeo/metabolismo , Líquido Cefalorraquídeo/fisiología , Nervios Periféricos/fisiología , Oro/química , Sistema Nervioso Periférico/fisiología , Nanopartículas del Metal/química , Sistema Nervioso Central/fisiología , Sistema Nervioso Central/metabolismo , Barrera Hematoencefálica/metabolismo , Ratas , RatonesRESUMEN
The peripheral nervous system consists of ganglia, nerve trunks, plexuses, and nerve endings, that transmit afferent and efferent information. Regeneration after a peripheral nerve damage is sluggish and imperfect. Peripheral nerve injury frequently causes partial or complete loss of motor and sensory function, physical impairment, and neuropathic pain, all of which have a negative impact on patients' quality of life. Because the mechanism of peripheral nerve injury and healing is still unclear, the therapeutic efficacy is limited. As peripheral nerve injury research has processed, an increasing number of studies have revealed that biological scaffolds work in tandem with progenitor cells to repair peripheral nerve injury. Here, we fabricated collagen chitosan nerve conduit bioscaffolds together with collagen and then filled neuroepithelial stem cells (NESCs). Scanning electron microscopy showed that the NESCs grew well on the scaffold surface. Compared to the control group, the NESCs group contained more cells with bigger diameters and myelinated structures around the axons. Our findings indicated that a combination of chitosan-collagen bioscaffold and neural stem cell transplantation can facilitate the functional restoration of peripheral nerve tissue, with promising future applications and research implications.
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Quitosano , Colágeno , Regeneración Nerviosa , Traumatismos de los Nervios Periféricos , Andamios del Tejido , Quitosano/química , Regeneración Nerviosa/fisiología , Colágeno/química , Animales , Andamios del Tejido/química , Traumatismos de los Nervios Periféricos/terapia , Ratas , Células Neuroepiteliales/citología , Células-Madre Neurales/citología , Nervios Periféricos/fisiología , Nervio Ciático/fisiologíaRESUMEN
The dorsal root ganglia (DRG), housing primary sensory neurons, transmit somatosensory and visceral afferent inputs to the dorsal horn of the spinal cord. They play a pivotal role in both physiological and pathological states, including neuropathic and visceral pain. In vivo calcium imaging of DRG enables real-time observation of calcium transients in single units or neuron ensembles. Accumulating evidence indicates that DRG neuronal activities induced by somatic stimulation significantly affect autonomic and visceral functions. While lumbar DRG calcium imaging has been extensively studied, thoracic segment DRG calcium imaging has been less explored due to surgical exposure and stereotaxic fixation challenges. Here, we utilized in vivo calcium imaging at the thoracic1 dorsal root ganglion (T1-DRG) to investigate changes in neuronal activity resulting from somatic stimulations of the forelimb. This approach is crucial for understanding the somato-cardiac reflex triggered by peripheral nerve stimulations (PENS), such as acupuncture. Notably, synchronization of cardiac function was observed and measured by electrocardiogram (ECG), with T-DRG neuronal activities, potentially establishing a novel paradigm for somato-visceral reflex in the thoracic segments.
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Calcio , Electrocardiografía , Ganglios Espinales , Animales , Ganglios Espinales/fisiología , Calcio/metabolismo , Calcio/análisis , Electrocardiografía/métodos , Ratones , Nervios Periféricos/fisiología , Miembro Anterior/inervación , Miembro Anterior/fisiologíaRESUMEN
Electroceuticals, through the selective modulation of peripheral nerves near target organs, are promising for treating refractory diseases. However, the small sizes and the delicate nature of these nerves present challenges in simplifying the fixation and stabilizing the electrical-coupling interface for neural electrodes. Herein, we construct a robust neural interface for fine peripheral nerves using an injectable bio-adhesive hydrogel bioelectronics. By incorporating a multifunctional molecular regulator during network formation, we optimize the injectability and conductivity of the hydrogel through fine-tuning reaction kinetics and multi-scale interactions within the conductive network. Meanwhile, the mechanical and electrical stability of the hydrogel is achieved without compromising its injectability. Minimal tissue damage along with low and stable impedance of the injectable neural interface enables chronic vagus neuromodulation for myocardial infarction therapy in the male rat model. Our highly-stable, injectable, conductive hydrogel bioelectronics are readily available to target challenging anatomical locations, paving the way for future precision bioelectronic medicine.
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Conductividad Eléctrica , Hidrogeles , Animales , Masculino , Hidrogeles/química , Ratas , Ratas Sprague-Dawley , Infarto del Miocardio/terapia , Inyecciones , Modelos Animales de Enfermedad , Nervio Vago/fisiología , Estimulación del Nervio Vago/métodos , Estimulación del Nervio Vago/instrumentación , Nervios Periféricos/fisiologíaRESUMEN
An intratissual electrical stimulation, accompanied by irritation of their central neurons, is used to recover the function of damaged peripheral nerves. Treatment results exceeded those with the use of cutaneous electrical stimulation, which is confirmed by comparative results of trial animal experiments. The time and quality of peripheral nerves' function recovery in comparison of intratissual and cutaneous electrical stimulation methods remain unknown. OBJECTIVE: To evaluate the time and quality of peripheral nerves' functions recovery after their suturing and conducting two different methods of electrical stimulation, namely intratissual and cutaneous, in projection of central neurons of damaged spinal nerves in the postoperative period. MATERIAL AND METHODS: The basic technical parameters of the method of peripheral nerves' functions recovery in the postoperative period were ptacticed. Postoperative rehabilitation treatment was performed in 77 patients with traumatic peripheral nerves' injuries at the level of the forearm: in 42 with intratissual electrical stimulation, in 35 - using cutaneous one with similar characteristics of electrical current and concomitant pharmacological therapy. The follow-up duration was 2 years. RESULTS: A significant (in 4-6 times) reduction in time of treatment and a greater improvement in qualitative indicators when using intratissual electrical stimulation compared to the use of cutaneous stimulation were obtained. The effectiveness of the restorative therapy was dependent on the number of procedures, and a complete recovery of the damaged peripheral nerves' functions was observed after three courses of intratissual electrical stimulation. CONCLUSION: The time and degree of recovery of peripheral nerves' functions depends on the functional activity of their central neurons at the level of the spinal cord. The activation of these neurons by low-frequency electrical current allows to activate their trophic function. Thus, the cutaneous electrical stimulation does not cause the necessary level of irritation of the neurons due to the fact that the skin is a barrier to electrical current, which reduces its impact in 200-500 times. The intratissual electrical stimulation allows to solve the problem by supplying the needle-electrode much closer to the «target¼. The proposed method of intratissual electrical stimulation has shown its advantage over cutaneous electrical stimulation, significantly reducing the duration of the restorative treatment and increasing its qualitative indicators.
Asunto(s)
Nervios Periféricos , Humanos , Masculino , Femenino , Nervios Periféricos/fisiología , Adulto , Traumatismos de los Nervios Periféricos/rehabilitación , Traumatismos de los Nervios Periféricos/terapia , Traumatismos de los Nervios Periféricos/fisiopatología , Terapia por Estimulación Eléctrica/métodos , Recuperación de la Función/fisiología , Persona de Mediana EdadRESUMEN
Implantable devices interfacing with peripheral nerves exhibit limited longevity and resolution. Poor nerve-electrode interface quality, invasive surgical placement and development of foreign body reaction combine to limit research and clinical application of these devices. Here, we develop cuff implants with a conformable design that achieve high-quality and stable interfacing with nerves in chronic implantation scenarios. When implanted in sensorimotor nerves of the arm in awake rats for 21 days, the devices record nerve action potentials with fascicle-specific resolution and extract from these the conduction velocity and direction of propagation. The cuffs exhibit high biocompatibility, producing lower levels of fibrotic scarring than clinically equivalent PDMS silicone cuffs. In addition to recording nerve activity, the devices are able to modulate nerve activity at sub-nerve resolution to produce a wide range of paw movements. When used in a partial nerve ligation rodent model, the cuffs identify and characterise changes in nerve C fibre activity associated with the development of neuropathic pain in freely-moving animals. The developed implantable devices represent a platform enabling new forms of fine nerve signal sensing and modulation, with applications in physiology research and closed-loop therapeutics.
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Potenciales de Acción , Nervios Periféricos , Animales , Nervios Periféricos/fisiología , Ratas , Potenciales de Acción/fisiología , Masculino , Electrodos Implantados , Neuralgia/fisiopatología , Neuralgia/terapia , Ratas Sprague-Dawley , Prótesis e Implantes , Conducción Nerviosa/fisiologíaRESUMEN
Peripheral nerve injury (PNI) represents a serious clinical and public health problem due to its high incurrence and poor spontaneous recovery. Compared to autograft, which is still the best current practice for long-gap peripheral nerve defects in clinics, the use of polymer-based biodegradable nerve guidance conduits (NGCs) has been gaining momentum as an alternative to guide the repair of severe PNI without the need of secondary surgery and donor nerve tissue. However, simple hollow cylindrical tubes can barely outperform autograft in terms of the regenerative efficiency especially in critical sized PNI. With the rapid development of tissue engineering technology and materials science, various functionalized NGCs have emerged to enhance nerve regeneration over the past decades. From the aspect of scaffold design considerations, with a specific focus on biodegradable polymers, this review aims to summarize the recent advances in NGCs by addressing the onerous demands of biomaterial selections, structural designs, and manufacturing techniques that contributes to the biocompatibility, degradation rate, mechanical properties, drug encapsulation and release efficiency, immunomodulation, angiogenesis, and the overall nerve regeneration potential of NGCs. In addition, several commercially available NGCs along with their regulation pathways and clinical applications are compared and discussed. Lastly, we discuss the current challenges and future directions attempting to provide inspiration for the future design of ideal NGCs that can completely cure long-gap peripheral nerve defects.
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Regeneración Nerviosa , Traumatismos de los Nervios Periféricos , Andamios del Tejido , Regeneración Nerviosa/fisiología , Humanos , Animales , Traumatismos de los Nervios Periféricos/terapia , Nervios Periféricos/fisiología , Materiales Biocompatibles , Ingeniería de Tejidos/métodos , Ingeniería de Tejidos/tendencias , Regeneración Tisular Dirigida/métodos , Regeneración Tisular Dirigida/tendencias , Regeneración Tisular Dirigida/instrumentaciónRESUMEN
Soft-tissue injuries affecting muscles, nerves, vasculature, tendons, and ligaments often diminish the quality of life due to pain, loss of function, and financial burdens. Both natural healing and surgical interventions can result in scarring, which potentially may impede functional recovery and lead to persistent pain. Scar tissue, characterized by a highly disorganized fibrotic extracellular matrix, may serve as a physical barrier to regeneration and drug delivery. While approaches such as drugs, biomaterials, cells, external stimulation, and other physical forces show promise in mitigating scarring and promoting regenerative healing, their implementation remains limited and challenging. Ultrasound, laser, electrical, and magnetic forms of external stimulation have been utilized to promote soft tissue as well as neural tissue regeneration. After stimulation, neural tissues experience increased proliferation of Schwann cells, secretion of neurotropic factors, production of myelin, and growth of vasculature, all aimed at supporting axon regeneration and innervation. Yet, the outcomes of healing vary depending on the pathophysiology of the damaged nerve, the timing of stimulation following injury, and the specific parameters of stimulation employed. Increased treatment intensity and duration have been noted to hinder the healing process by inducing tissue damage. These stimulation modalities, either alone or in combination with nerve guidance conduits and scaffolds, have been demonstrated to promote healing. However, the literature currently lacks a detailed understanding of the stimulation parameters used for nerve healing applications. In this article, we aim to address this gap by summarizing existing reports and providing an overview of stimulation parameters alongside their associated healing outcomes.
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Regeneración Nerviosa , Traumatismos de los Nervios Periféricos , Nervios Periféricos , Humanos , Animales , Nervios Periféricos/fisiología , Traumatismos de los Nervios Periféricos/terapia , Terapia por Estimulación Eléctrica/métodos , Cicatrización de Heridas , Andamios del Tejido , Células de SchwannRESUMEN
Peripheral nerve injury is a prevalent clinical problem that often leads to lifelong disability and reduced quality of life. Although peripheral nerves can regenerate, recovery after severe injury is slow and incomplete. The current gold standard treatment, autologous nerve transplantation, has limitations including donor site morbidity and poor functional outcomes, highlighting the need for improved repair strategies. We developed a reproducible in vitro hollow channel collagen gel construct to investigate peripheral nerve regeneration (PNR) by exploring the influence of key extracellular matrix (ECM) proteins on axonal growth and regeneration. Channels were coated with ECM proteins: collagen IV, laminin, or fibronectin and seeded with dorsal root ganglia (DRG) collected from E16 rat embryos to compare the ability of the ECM proteins to enhance axonal growth. Robust axonal extension and Schwann cell (SC) infiltration were observed in fibronectin-coated channels, suggesting its superiority over other ECM proteins. Differential effects of ECM proteins on axons and SCs indicated direct growth stimulation beyond SC-mediated guidance. In vitro laceration injury modeling further confirmed fibronectin's superior pro-regenerative effects, showcasing its potential in enhancing axonal regrowth post-injury. Advancing in vitro modeling that closely replicates native microenvironments will accelerate progress in overcoming the limitations of current nerve repair approaches.
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Proteínas de la Matriz Extracelular , Ganglios Espinales , Regeneración Nerviosa , Traumatismos de los Nervios Periféricos , Animales , Regeneración Nerviosa/fisiología , Ratas , Traumatismos de los Nervios Periféricos/terapia , Traumatismos de los Nervios Periféricos/metabolismo , Ganglios Espinales/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Axones/fisiología , Axones/metabolismo , Colágeno/metabolismo , Células de Schwann/metabolismo , Células de Schwann/fisiología , Fibronectinas/metabolismo , Ratas Sprague-Dawley , Andamios del Tejido/química , Nervios Periféricos/fisiología , Laminina/metabolismoRESUMEN
Electrical stimulation of peripheral nerves has been used in various pathological contexts for rehabilitation purposes or to alleviate the symptoms of neuropathologies, thus improving the overall quality of life of patients. However, the development of novel therapeutic strategies is still a challenging issue requiring extensive in vivo experimental campaigns and technical development. To facilitate the design of new stimulation strategies, we provide a fully open source and self-contained software framework for the in silico evaluation of peripheral nerve electrical stimulation. Our modeling approach, developed in the popular and well-established Python language, uses an object-oriented paradigm to map the physiological and electrical context. The framework is designed to facilitate multi-scale analysis, from single fiber stimulation to whole multifascicular nerves. It also allows the simulation of complex strategies such as multiple electrode combinations and waveforms ranging from conventional biphasic pulses to more complex modulated kHz stimuli. In addition, we provide automated support for stimulation strategy optimization and handle the computational backend transparently to the user. Our framework has been extensively tested and validated with several existing results in the literature.
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Biología Computacional , Simulación por Computador , Nervios Periféricos , Programas Informáticos , Nervios Periféricos/fisiología , Humanos , Estimulación Eléctrica/métodos , Terapia por Estimulación Eléctrica/métodos , Modelos NeurológicosRESUMEN
Objective.Peripheral nerve stimulation (PNS) has been demonstrated as an effective way to selectively activate muscles and to produce fine hand movements. However, sequential multi-joint upper limb movements, which are critical for paralysis rehabilitation, has not been tested with PNS. Here, we aimed to restore multiple upper limb joint movements through an intraneural interface with a single electrode, achieving coherent reach-grasp-pull movement tasks through sequential stimulation.Approach.A transverse intrafascicular multichannel electrode was implanted under the axilla of the rat's upper limb, traversing the musculocutaneous, radial, median, and ulnar nerves. Intramuscular electrodes were implanted into the biceps brachii (BB), triceps brachii (TB), flexor carpi radialis (FCR), and extensor carpi radialis (ECR) muscles to record electromyographic (EMG) activity and video recordings were used to capture the kinematics of elbow, wrist, and digit joints. Charge-balanced biphasic pulses were applied to different channels to recruit distinct upper limb muscles, with concurrent recording of EMG signals and joint kinematics to assess the efficacy of the stimulation. Finally, a sequential stimulation protocol was employed by generating coordinated pulses in different channels.Main results.BB, TB, FCR and ECR muscles were selectively activated and various upper limb movements, including elbow flexion, elbow extension, wrist flexion, wrist extension, digit flexion, and digit extension, were reliably generated. The modulation effects of stimulation parameters, including pulse width, amplitude, and frequency, on induced joint movements were investigated and reach-grasp-pull movement was elicited by sequential stimulation.Significance.Our results demonstrated the feasibility of sequential intraneural stimulation for functional multi-joint movement restoration, providing a new approach for clinical rehabilitation in paralyzed patients.
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Fuerza de la Mano , Movimiento , Nervios Periféricos , Ratas Sprague-Dawley , Animales , Ratas , Nervios Periféricos/fisiología , Movimiento/fisiología , Fuerza de la Mano/fisiología , Músculo Esquelético/fisiología , Músculo Esquelético/inervación , Masculino , Terapia por Estimulación Eléctrica/métodos , Electrodos Implantados , Electromiografía/métodosRESUMEN
Peripheral nerve stimulation (PNS) is an effective means to elicit sensation for rehabilitation of people with loss of a limb or limb function. While most current PNS paradigms deliver current through single electrode contacts to elicit each tactile percept, multi-contact extraneural electrodes offer the opportunity to deliver PNS with groups of contacts individually or simultaneously. Multi-contact PNS strategies could be advantageous in developing biomimetic PNS paradigms to recreate the natural neural activity during touch, because they may be able to selectively recruit multiple distinct neural populations. We used computational models and optimization approaches to develop a novel biomimetic PNS paradigm that uses interleaved multi-contact (IMC) PNS to approximate the critical neural coding properties underlying touch. The IMC paradigm combines field shaping, in which two contacts are active simultaneously, with pulse-by-pulse contact and parameter variations throughout the touch stimulus. We show in simulation that IMC PNS results in better neural code mimicry than single contact PNS created with the same optimization techniques, and that field steering via two-contact IMC PNS results in better neural code mimicry than one-contact IMC PNS. We also show that IMC PNS results in better neural code mimicry than existing PNS paradigms, including prior biomimetic PNS. Future clinical studies will determine if the IMC paradigm can improve the naturalness and usefulness of sensory feedback for those with neurological disorders.
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Simulación por Computador , Nervios Periféricos , Tacto , Humanos , Tacto/fisiología , Nervios Periféricos/fisiología , Modelos Neurológicos , Biomimética , Algoritmos , Electrodos , Estimulación Eléctrica Transcutánea del Nervio/métodos , Percepción del Tacto/fisiologíaRESUMEN
Optoelectronic neural interfaces can leverage the photovoltaic effect to convert light into electrical current, inducing charge redistribution and enabling nerve stimulation. This method offers a non-genetic and remote approach for neuromodulation. Developing biodegradable and efficient optoelectronic neural interfaces is important for achieving transdermal stimulation while minimizing infection risks associated with device retrieval, thereby maximizing therapeutic outcomes. We propose a biodegradable, flexible, and miniaturized silicon-based neural interface capable of transdermal optoelectronic stimulation for neural modulation and nerve regeneration. Enhancing the device interface with thin-film molybdenum significantly improves the efficacy of neural stimulation. Our study demonstrates successful activation of the sciatic nerve in rodents and the facial nerve in rabbits. Moreover, transdermal optoelectronic stimulation accelerates the functional recovery of injured facial nerves.
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Regeneración Nerviosa , Nervio Ciático , Animales , Conejos , Regeneración Nerviosa/fisiología , Regeneración Nerviosa/efectos de los fármacos , Nervio Ciático/fisiología , Nervio Facial/fisiología , Nervios Periféricos/fisiología , Masculino , Ratas , Silicio/química , Ratas Sprague-Dawley , Estimulación EléctricaRESUMEN
Limb neuroprostheses aim to restore motor and sensory functions in amputated or severely nerve-injured patients. These devices use neural interfaces to record and stimulate nerve action potentials, creating a bidirectional connection with the nervous system. Most neural interfaces are based on standard metal microelectrodes. In this work, a new generation of neural interfaces which replaces metals with engineered graphene, called EGNITE, is tested. In vitro and in vivo experiments are conducted to assess EGNITE biocompatibility. In vitro tests show that EGNITE does not impact cell viability. In vivo, no significant functional decrease or harmful effects are observed. Furthermore, the foreign body reaction to the intraneural implant is similar compared to other materials previously used in neural interfaces. Regarding functionality, EGNITE devices are able to stimulate nerve fascicles, during two months of implant, producing selective muscle activation with about three times less current compared to larger microelectrodes of standard materials. CNAP elicited by electrical stimuli and ENG evoked by mechanical stimuli are recorded with high resolution but are more affected by decreased functionality over time. This work constitutes further proof that graphene-derived materials, and specifically EGNITE, is a promising conductive material of neural electrodes for advanced neuroprostheses.
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Grafito , Nervios Periféricos , Grafito/química , Animales , Nervios Periféricos/fisiología , Ratas , Electrodos Implantados , Materiales Biocompatibles , Microelectrodos , Potenciales de Acción/fisiología , MasculinoRESUMEN
Research to improve and expand treatment options for motor impairment after stroke remains an important issue in rehabilitation as the reduced ability to move affected limbs is still a limiting factor in the selection of training content for stroke patients. The combination of action observation and peripheral nerve stimulation is a promising method for inducing increased excitability and plasticity in the primary motor cortex of healthy subjects. In addition, as reported in the literature, the use of action observation and motor imagery in conjunction has an advantage over the use of one or the other alone in terms of the activation of motor-related brain regions. The aim of the pilot study was thus to combine these findings into a multimodal approach and to evaluate the potential impact of the concurrent application of the three methods on dexterity in stroke patients. The paradigm developed accordingly was tested with 10 subacute patients, in whom hand dexterity, thumb-index pinch force and thumb tapping speed were measured for a baseline assessment and directly before and after the single intervention. During the 10-min session, patients were instructed to watch a repetitive thumb-index finger tapping movement displayed on a monitor and to imagine the sensations that would arise from physically performing the same motion. They were also repeatedly electrically stimulated at the wrist on the motorically more affected body side and asked to place their hand behind the monitor for the duration of the session to support integration of the displayed hand into their own body schema. The data provide a first indication of a possible immediate effect of a single application of this procedure on the dexterity in patients after stroke.
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Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Proyectos Piloto , Masculino , Femenino , Persona de Mediana Edad , Anciano , Accidente Cerebrovascular/fisiopatología , Accidente Cerebrovascular/terapia , Rehabilitación de Accidente Cerebrovascular/métodos , Corteza Motora/fisiopatología , Nervios Periféricos/fisiopatología , Nervios Periféricos/fisiología , Imágenes en Psicoterapia/métodos , Adulto , Destreza Motora/fisiología , Estimulación Eléctrica/métodosRESUMEN
Objective.To develop a clinically relevant injectable hydrogel derived from decellularized porcine peripheral nerves and with mechanical properties comparable to native central nervous system (CNS) tissue to be used as a delivery vehicle for Schwann cell transplantation to treat spinal cord injury (SCI).Approach.Porcine peripheral nerves (sciatic and peroneal) were decellularized by chemical decellularization using a sodium deoxycholate and DNase (SDD) method previously developed by our group. The decellularized nerves were delipidated using dichloromethane and ethanol solvent and then digested using pepsin enzyme to form injectable hydrogel formulations. Genipin was used as a crosslinker to enhance mechanical properties. The injectability, mechanical properties, and gelation kinetics of the hydrogels were further analyzed using rheology. Schwann cells encapsulated within the injectable hydrogel formulations were passed through a 25-gauge needle and cell viability was assessed using live/dead staining. The ability of the hydrogel to maintain Schwann cell viability against an inflammatory milieu was assessedin vitrousing inflamed astrocytes co-cultured with Schwann cells.Mainresults. The SDD method effectively removes cells and retains extracellular matrix in decellularized tissues. Using rheological studies, we found that delipidation of decellularized porcine peripheral nerves using dichloromethane and ethanol solvent improves gelation kinetics and mechanical strength of hydrogels. The delipidated and decellularized hydrogels crosslinked using genipin mimicked the mechanical strength of CNS tissue. The hydrogels were found to have shear thinning properties desirable for injectable formulations and they also maintained higher Schwann cell viability during injection compared to saline controls. Usingin vitroco-culture experiments, we found that the genipin-crosslinked hydrogels also protected Schwann cells from astrocyte-mediated inflammation.Significance. Injectable hydrogels developed using delipidated and decellularized porcine peripheral nerves are a potential clinically relevant solution to deliver Schwann cells, and possibly other therapeutic cells, at the SCI site by maintaining higher cellular viability and increasing therapeutic efficacy for SCI treatment.
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Hidrogeles , Nervios Periféricos , Células de Schwann , Traumatismos de la Médula Espinal , Animales , Células de Schwann/fisiología , Células de Schwann/efectos de los fármacos , Hidrogeles/química , Hidrogeles/administración & dosificación , Porcinos , Traumatismos de la Médula Espinal/terapia , Nervios Periféricos/fisiología , Nervios Periféricos/efectos de los fármacos , Regeneración de la Medula Espinal/fisiología , Regeneración de la Medula Espinal/efectos de los fármacos , Células Cultivadas , Supervivencia Celular/fisiología , Supervivencia Celular/efectos de los fármacosRESUMEN
Ultrasound imaging is an essential tool in anesthesiology, particularly for ultrasound-guided peripheral nerve blocks (US-PNBs). However, challenges such as speckle noise, acoustic shadows, and variability in nerve appearance complicate the accurate localization of nerve tissues. To address this issue, this study introduces a deep convolutional neural network (DCNN), specifically Scaled-YOLOv4, and investigates an appropriate network model and input image scaling for nerve detection on ultrasound images. Utilizing two datasets, a public dataset and an original dataset, we evaluated the effects of model scale and input image size on detection performance. Our findings reveal that smaller input images and larger model scales significantly improve detection accuracy. The optimal configuration of model size and input image size not only achieved high detection accuracy but also demonstrated real-time processing capabilities.
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Bloqueo Nervioso , Redes Neurales de la Computación , Ultrasonografía , Bloqueo Nervioso/métodos , Humanos , Ultrasonografía/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Nervios Periféricos/diagnóstico por imagen , Nervios Periféricos/fisiología , Ultrasonografía Intervencional/métodosRESUMEN
BACKGROUND: The fundamental prerequisite for prognostically favorable postoperative results of peripheral nerve repair is stable neurorrhaphy without interruption and gap formation. METHODS: This study evaluates 60 neurorrhaphies on femoral chicken nerves in terms of the procedure and the biomechanical properties. Sutured neurorrhaphies (n = 15) served as control and three sutureless adhesive-based nerve repair techniques: Fibrin glue (n = 15), Histoacryl glue (n = 15), and the novel polyurethane adhesive VIVO (n = 15). Tensile and elongation tests of neurorrhaphies were performed on a tensile testing machine at a displacement rate of 20 mm/min until failure. The maximum tensile force and elongation were recorded. RESULTS: All adhesive-based neurorrhaphies were significant faster in preparation compared to sutured anastomoses (p < 0.001). Neurorrhaphies by sutured (102.8 [cN]; p < 0.001), Histoacryl (91.5 [cN]; p < 0.001) and VIVO (45.47 [cN]; p < 0.05) withstood significant higher longitudinal tensile forces compared to fibrin glue (10.55 [cN]). VIVO, with â³L/L0 of 6.96 [%], showed significantly higher elongation (p < 0.001) compared to neurorrhaphy using fibrin glue. CONCLUSION: Within the limitations of an in vitro study the adhesive-based neurorrhaphy technique with VIVO and Histoacryl have the biomechanical potential to offer alternatives to sutured neuroanastomosis because of their stability, and faster handling. Further in vivo studies are required to evaluate functional outcomes and confirm safety.
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Anastomosis Quirúrgica , Pollos , Resistencia a la Tracción , Animales , Anastomosis Quirúrgica/métodos , Fenómenos Biomecánicos , Adhesivos Tisulares/farmacología , Adhesivo de Tejido de Fibrina/farmacología , Nervios Periféricos/cirugía , Nervios Periféricos/fisiología , Adhesivos , Procedimientos Neuroquirúrgicos/métodosRESUMEN
Peripheral nerve injuries (PNIs) frequently occur due to various factors, including mechanical trauma such as accidents or tool-related incidents, as well as complications arising from diseases like tumor resection. These injuries frequently result in persistent numbness, impaired motor and sensory functions, neuropathic pain, or even paralysis, which can impose a significant financial burden on patients due to outcomes that often fall short of expectations. The most frequently employed clinical treatment for PNIs involves either direct sutures of the severed ends or bridging the proximal and distal stumps using autologous nerve grafts. However, autologous nerve transplantation may result in sensory and motor functional loss at the donor site, as well as neuroma formation and scarring. Transplantation of Schwann cells/Schwann cell-like cells has emerged as a promising cellular therapy to reconstruct the microenvironment and facilitate peripheral nerve regeneration. In this review, we summarize the role of Schwann cells and recent advances in Schwann cell therapy in peripheral nerve regeneration. We summarize current techniques used in cell therapy, including cell injection, 3D-printed scaffolds for cell delivery, cell encapsulation techniques, as well as the cell types employed in experiments, experimental models, and research findings. At the end of the paper, we summarize the challenges and advantages of various cells (including ESCs, iPSCs, and BMSCs) in clinical cell therapy. Our goal is to provide the theoretical and experimental basis for future treatments targeting peripheral nerves, highlighting the potential of cell therapy and tissue engineering as invaluable resources for promoting nerve regeneration.
Asunto(s)
Regeneración Nerviosa , Traumatismos de los Nervios Periféricos , Células de Schwann , Células de Schwann/fisiología , Humanos , Animales , Regeneración Nerviosa/fisiología , Traumatismos de los Nervios Periféricos/terapia , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Nervios Periféricos/fisiologíaRESUMEN
One hundred years ago, Erlanger and Gasser demonstrated that conduction velocity is correlated with the diameter of a peripheral nerve axon. Later, they also demonstrated that the functional role of the axon is related to its diameter: touch is signalled by large-diameter axons, whereas pain and temperature are signalled by small-diameter axons. Certain discoveries in recent decades prompt a modification of this canonical classification. Here, we review the evidence for unmyelinated (C) fibres signalling touch at a slow conduction velocity and likely contributing to affective aspects of tactile information. We also review the evidence for large-diameter Aß afferents signalling pain at ultrafast conduction velocity and likely contributing to the rapid nociceptive withdrawal reflex. These discoveries imply that conduction velocity is not as clear-cut an indication of the functional role of the axon as previously thought. We finally suggest that a future taxonomy of the peripheral afferent nervous system might be based on the combination of the axons molecular expression and electrophysiological response properties.