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1.
Life Sci ; 243: 117308, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31954163

RESUMO

Compromised functional regains in about half of the patients following surgical nerve repair pose a serious socioeconomic burden to the society. Although surgical strategies such as end-to-end neurorrhaphy, nerve grafting and nerve transfer are widely applied in distal injuries leading to optimal recovery; however in proximal nerve defects functional outcomes remain unsatisfactory. Biomedical engineering approaches unite the efforts of the surgeons, engineers and biologists to develop regeneration facilitating structures such as extracellular matrix based supportive polymers and tubular nerve guidance channels. Such polymeric structures provide neurotrophic support from injured nerve stumps, retard the fibrous tissue infiltration and guide regenerating axons to appropriate targets. The development and application of nerve guidance conduits (NGCs) to treat nerve gap injuries offer clinically relevant and feasible solutions. Enhanced understanding of the nerve regeneration processes and advances in NGCs design, polymers and fabrication strategies have led to developing modern NGCs with superior regeneration-conducive capacities. Current review focuses on the advances in surgical and engineering approaches to treat peripheral nerve injuries. We suggest the incorporation of endothelial cell growth promoting cues and factors into the NGC interior for its possible enhancement effects on the axonal regeneration process that may result in substantial functional outcomes.


Assuntos
Traumatismos dos Nervos Periféricos/terapia , Animais , Materiais Biocompatíveis , Humanos , Regeneração Nervosa/fisiologia
2.
Nat Commun ; 10(1): 5782, 2019 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-31857587

RESUMO

Nerve damage can cause chronic, debilitating problems including loss of motor control and paresthesia, and generates maladaptive neuroplasticity as central networks attempt to compensate for the loss of peripheral connectivity. However, it remains unclear if this is a critical feature responsible for the expression of symptoms. Here, we use brief bursts of closed-loop vagus nerve stimulation (CL-VNS) delivered during rehabilitation to reverse the aberrant central plasticity resulting from forelimb nerve transection. CL-VNS therapy drives extensive synaptic reorganization in central networks paralleled by improved sensorimotor recovery without any observable changes in the nerve or muscle. Depleting cortical acetylcholine blocks the plasticity-enhancing effects of CL-VNS and consequently eliminates recovery, indicating a critical role for brain circuits in recovery. These findings demonstrate that manipulations to enhance central plasticity can improve sensorimotor recovery and define CL-VNS as a readily translatable therapy to restore function after nerve damage.


Assuntos
Plasticidade Neuronal/fisiologia , Traumatismos dos Nervos Periféricos/terapia , Estimulação do Nervo Vago , Animais , Modelos Animais de Doenças , Feminino , Membro Anterior/inervação , Membro Anterior/cirurgia , Humanos , Rede Nervosa/fisiologia , Traumatismos dos Nervos Periféricos/etiologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Resultado do Tratamento
3.
Unfallchirurg ; 122(11): 860-863, 2019 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-31712851

RESUMO

A small portion of patients suffer from severe knee pain following previous knee surgery or a trauma. Awareness among traumatologists regarding a neuropathic origin of this persistent knee pain is poor. Ongoing pain close to the knee may be caused by damage of the infrapatellar nerve (IN). This branch of the saphenous nerve is purely sensory and is at risk for iatrogenic damage due to its superficial medial course. Once recognized using simple tests during physical examination, a variety of treatment modalities may be proposed. However, a standard treatment algorithm was hitherto absent. This study includes 15 patients having IN damage who were offered a step-up regimen including lidocaine injections, pulsed radiofrequency (PRF) or neurectomy. Success (>50% drop in numeric rating scale pain score) was attained in 11 (73% success rate, 9 month median follow-up). The aim of this contribution is to increase knowledge regarding this illusive entity and to discuss the efficacy of our treatment protocol.


Assuntos
Nervo Femoral/lesões , Dor/etiologia , Traumatismos dos Nervos Periféricos/terapia , Denervação , Humanos , Perna (Membro)/inervação , Dor/diagnóstico , Manejo da Dor , Medição da Dor , Traumatismos dos Nervos Periféricos/etiologia , Resultado do Tratamento
4.
Biomed Res Int ; 2019: 6458237, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31531362

RESUMO

Although significant advances have been made in synthetic nerve conduits and surgical techniques, complete regeneration following peripheral nerve injury (PNI) remains far from optimized. The repair of PNI is a highly heterogeneous process involving changes in Schwann cell phenotypes, the activation of macrophages, and the reconstruction of the vascular network. At present, the efficacy of MSC-based therapeutic strategies for PNI can be attributed to paracrine secretion. Exosomes, as a product of paracrine secretion, are considered to be an important regulatory mediator. Furthermore, accumulating evidence has demonstrated that exosomes from mesenchymal stem cells (MSCs) can shuttle bioactive components (proteins, lipids, mRNA, miRNA, lncRNA, circRNA, and DNA) that participate in almost all of the abovementioned processes. Thus, MSC exosomes may represent a novel therapeutic tool for PNI. In this review, we discuss the current understanding of MSC exosomes related to peripheral nerve repair and provide insights for developing a cell-free MSC therapeutic strategy for PNI.


Assuntos
Exossomos/fisiologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/fisiologia , Traumatismos dos Nervos Periféricos/terapia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Humanos , Comunicação Parácrina/fisiologia , Regeneração/fisiologia , Células de Schwann/citologia
5.
J Mater Sci Mater Med ; 30(9): 107, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31512084

RESUMO

In the present study, collagen hydrogel containing naringin was fabricated, characterized and used as the scaffold for peripheral nerve damage treatment. The collagen was dissolved in acetic acid, naringin added to the collagen solution, and cross-linked with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide powder (EDC; 0.10 mM) to form the hydrogel. The microstructure, swelling behavior, biodegradation, and cyto/hemocompatibility of the fabricated hydrogels were assessed. Finally, the healing efficacy of the prepared collagen hydrogel loaded with naringin on the sciatic nerve crush injury was assessed in the animal model. The characterization results showed that the fabricated hydrogels have a porous structure containing interconnected pores with the average pore size of 90 µm. The degradation results demonstrated that about 70% of the primary weight of the naringin loaded hydrogel had been lost after 4 weeks of storage in PBS. The in vitro study showed that the proliferation of Schwann cells on the collagen/naringin hydrogel was higher than the control group (tissue culture plate) at both 48 and 72 h after cell seeding and even significantly higher than pure collagen 72 h after cell seeding (*p < 0.005, **p < 0.001). The animal study implied that the sciatic functional index reached to -22.13 ± 3.00 at the end of 60th days post-implantation which was statistically significant (p < 0.05) compared with the negative control (injury without the treatment) (-82.60 ± 1.06), and the pure collagen hydrogel (-59.80 ± 3.20) groups. The hot plate latency test, the compound muscle action potential, and wet weight-loss of the gastrocnemius muscle evaluation confirmed the positive effect of the prepared hydrogels on the healing process of the induced nerve injury. In the final, the histopathologic examinations depicted that the collagen/naringin hydrogel group reduced all the histological changes induced from the nerve injury and showed more resemblance to the normal sciatic nerve, with well-arranged fibers and intact myelin sheath. The overall results implied that the prepared collagen/naringin hydrogel can be utilized as a sophisticated alternative to healing peripheral nerve damages.


Assuntos
Colágeno Tipo I/química , Flavanonas/farmacologia , Regeneração Tecidual Guiada/métodos , Hidrogéis/farmacologia , Regeneração Nervosa/efeitos dos fármacos , Nervo Isquiático/lesões , Nervo Isquiático/fisiologia , Animais , Células Cultivadas , Colágeno Tipo I/farmacologia , Flavanonas/química , Humanos , Hidrogéis/química , Masculino , Teste de Materiais , Traumatismos dos Nervos Periféricos/patologia , Traumatismos dos Nervos Periféricos/terapia , Ratos , Ratos Wistar , Células de Schwann/citologia , Células de Schwann/efeitos dos fármacos , Células de Schwann/fisiologia , Nervo Isquiático/efeitos dos fármacos , Tecidos Suporte/química , Cicatrização/efeitos dos fármacos
6.
J Bone Joint Surg Am ; 101(16): e80, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31436660

RESUMO

BACKGROUND: Traumatic brachial plexus injuries (BPIs) disproportionately affect young, able-bodied individuals. Beyond direct costs associated with medical treatment, there are far-reaching indirect costs related to disability and lost productivity. Our objective was to estimate per-patient indirect cost associated with BPI. METHODS: We estimated indirect costs as the sum of (1) short-term wage loss, (2) long-term wage loss, and (3) disability payments. Short-term (6-month) wage loss was the product of missed work days and the average earnings per day. The probability of return to work was derived from a systematic review of the literature, and long-term wage loss and disability payments were estimated. Monte Carlo simulation was used to perform a sensitivity analysis of long-term wage loss by varying age, sex, and return to work simultaneously. Disability benefits were estimated from U.S. Social Security Administration data. All cost estimates are in 2018 U.S. dollars. RESULTS: A systematic review of the literature demonstrated that the patients with BPI had a mean age of 26.4 years, 90.5% were male, and manual labor was the most represented occupation. On the basis on these demographics, our base case was a 26-year-old American man working as a manual laborer prior to BPI, with an annual wage of $36,590. Monte Carlo simulation estimated a short-term wage loss of $22,740, a long-term wage loss of $737,551, and disability benefits of $353,671. The mean total indirect cost of traumatic BPI in the Monte Carlo simulations was $1,113,962 per patient over the post-injury lifetime (median: $801,723, interquartile range: $22,740 to $2,350,979). If the probability of the patient returning to work at a different, lower-paying job was doubled, the per-patient total indirect cost was $867,987. CONCLUSIONS: BPI can have a far-reaching economic impact on both individuals and society. If surgical reconstruction enables patients with a BPI to return to work, the indirect cost of this injury decreases. LEVEL OF EVIDENCE: Economic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Plexo Braquial/lesões , Efeitos Psicossociais da Doença , Avaliação da Deficiência , Traumatismos dos Nervos Periféricos/economia , Traumatismos dos Nervos Periféricos/terapia , Ferimentos e Lesões/complicações , Adulto , Neuropatias do Plexo Braquial/economia , Neuropatias do Plexo Braquial/etiologia , Neuropatias do Plexo Braquial/terapia , Análise Custo-Benefício , Feminino , Custos de Cuidados de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Método de Monte Carlo , Traumatismos dos Nervos Periféricos/diagnóstico , Retorno ao Trabalho/economia , Estados Unidos , Adulto Jovem
7.
Chin Med J (Engl) ; 132(14): 1706-1712, 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31261200

RESUMO

BACKGROUND: Pulsed radiofrequency (PRF) is a minimally invasive interventional technique that provides a novel and effective treatment strategy for neuropathic pain (NP). PRF is advantageous because it does not damage nerves and avoids sensory loss after treatment. At present, animal studies have demonstrated that PRF is safe and effective for relieving the NP associated with sciatic nerve damage in rats with chronic constriction injury (CCI). However, the mechanism through which this effect occurs is unknown. An increasing body of evidence shows that the expression of the P2X ligand-gated ion channel 3 (P2X3) receptor is closely related to NP; this study was to investigate whether the expression of this receptor is involved in NP relief due to PRF. METHODS: A total of 36 healthy adult male Sprague-Dawley (SD) rats were randomly divided into three groups: Sham group, CCI group, and PRF group. The right sciatic nerve was ligated in CCI group and PRF group to establish a CCI model; the right sciatic nerve was separated but not ligated in Sham group. On day 14 after the operation, PRF was administered to the ligated sciatic nerve in PRF group (42°C, 45 V, 2 min). A non-live electrode was placed at the exposed sciatic nerve for the rats in Sham and CCI groups. The hindpaw withdrawal threshold (HWT) and thermal withdrawal latency (TWL) were measured at the right hindpaw at different time points before and after PRF or sham therapy. On day 28 after treatment, the dorsal root ganglion (DRG) and spinal dorsal horn of the right L4-6 were harvested from each group to determine the mRNA and protein levels of the P2X3 receptor. RESULTS: On day 28 after PRF treatment, the HWT (8.33 ±â€Š0.67 g vs. 3.62 ±â€Š0.48 g) and TWL (25.42 ±â€Š1.90 s vs. 15.10 ±â€Š1.71 s) were significantly higher in PRF group as compared to CCI group (P < 0.05). The mRNA expression of the P2X3 receptor in the DRG in PRF group was 23.7% lower than that in CCI group (P < 0.05), in the spinal dorsal horns in PRF group was 22.7% lower than that in CCI group (P < 0.05). The protein expression of the P2X3 receptor in the DRG in PRF group was 27.8% lower than that in CCI group (P < 0.05), in the spinal dorsal horns in PRF group was 35.6% lower than that in CCI group (P < 0.05). CONCLUSION: PRF possibly reduces NP in CCI rats by inhibiting the expression of the P2X3 receptor in the L4-6 DRG and spinal dorsal horns.


Assuntos
Constrição , Neuralgia/metabolismo , Neuralgia/terapia , Traumatismos dos Nervos Periféricos/metabolismo , Traumatismos dos Nervos Periféricos/terapia , Tratamento por Radiofrequência Pulsada/métodos , Receptores Purinérgicos P2X3/metabolismo , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Neuropatia Ciática/metabolismo , Neuropatia Ciática/terapia
8.
Eur Arch Otorhinolaryngol ; 276(11): 3185-3193, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31338575

RESUMO

PURPOSE: Periauricular sensory deficit occurs frequently after parotidectomy even in cases with preservation of the greater auricular nerve (GAN). This study was performed to evaluate the effects of antiadhesive agent in functional recovery of the GAN after parotidectomy. METHODS: Ninety-eight patients undergoing partial parotidectomy for benign parotid tumors were prospectively enrolled in this multicenter, double-blind randomized controlled study and randomly assigned to either the study or control group. Antiadhesive agent was applied in the study group. The results of sensory tests (tactile, heat, and cold sensitivity) and a questionnaire on quality of life (QoL) were acquired at postoperative 1, 8, and 24 weeks after surgery. Clinical parameters, and the results of the sensory tests and the questionnaire, were compared between the two groups. RESULTS: A total of 80 patients were finally enrolled. On sensory evaluation, tactile sensation and warm sensation in the ear lobule, and warm sensation in the mastoid area, showed significant improvement at 24 weeks postoperatively in the study group. There were no significant differences between the two groups on any questions in the QoL questionnaire, at any follow-up time point. CONCLUSIONS: Antiadhesive agents have some positive effects on functional recovery of the GAN after parotidectomy. Therefore, applying antiadhesive agents after parotidectomy can reduce discomfort in patients.


Assuntos
Agnosia , Plexo Cervical/lesões , Dissecação , Glândula Parótida/cirurgia , Neoplasias Parotídeas/cirurgia , Traumatismos dos Nervos Periféricos , Aderências Teciduais , Agnosia/diagnóstico , Agnosia/etiologia , Agnosia/terapia , Dissecação/efeitos adversos , Dissecação/métodos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Glândula Parótida/patologia , Neoplasias Parotídeas/patologia , Região Parotídea/inervação , Região Parotídea/cirurgia , Traumatismos dos Nervos Periféricos/diagnóstico , Traumatismos dos Nervos Periféricos/etiologia , Traumatismos dos Nervos Periféricos/terapia , Recuperação de Função Fisiológica/fisiologia , Aderências Teciduais/etiologia , Aderências Teciduais/prevenção & controle , Resultado do Tratamento
9.
Cell Prolif ; 52(5): e12660, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31264327

RESUMO

OBJECTIVES: Muscle spindles are proprioceptive receptors in the skeletal muscle. Peripheral nerve injury results in a decreased number of muscle spindles and their morphologic deterioration. However, the muscle spindles recover when skeletal muscles are reinnervated with surgical procedures, such as nerve suture or nerve transfer. Morphological changes in muscle spindles by cell transplantation procedure have not been reported so far. Therefore, we hypothesized that transplantation of embryonic sensory neurons may improve sensory neurons in the skeletal muscle and reinnervate the muscle spindles. MATERIALS AND METHODS: We collected sensory neurons from dorsal root ganglions of 14-day-old rat embryos and prepared a rat model of peripheral nerve injury by performing sciatic nerve transection and allowing for a period of one week before which we performed the cell transplantations. Six months later, the morphological changes of muscle spindles in the cell transplantation group were compared with the naïve control and surgical control groups. RESULTS: Our results demonstrated that transplantation of embryonic dorsal root ganglion cells induced regeneration of sensory nerve fibre and reinnervation of muscle spindles in the skeletal muscle. Moreover, calbindin D-28k immunoreactivity in intrafusal muscle fibres was maintained for six months after denervation in the cell transplantation group, whereas it disappeared in the surgical control group. CONCLUSIONS: Cell transplantation therapies could serve as selective targets to modulate mechanosensory function in the skeletal muscle.


Assuntos
Gânglios Espinais/transplante , Fusos Musculares/metabolismo , Traumatismos dos Nervos Periféricos/terapia , Animais , Calbindinas/metabolismo , Embrião de Mamíferos/citologia , Gânglios Espinais/citologia , Gânglios Espinais/metabolismo , Masculino , Fibras Nervosas/fisiologia , Ratos , Ratos Endogâmicos F344 , Regeneração , Nervo Tibial/metabolismo , Nervo Tibial/patologia
10.
J Orthop Res ; 37(10): 2258-2263, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31115924

RESUMO

Autologous vein wrapping is used to treat recurrent chronic constriction neuropathy and traumatic peripheral nerve injury. However, its use is restricted due to the inability to obtain sufficiently long veins for larger grafts. We previously reported that vein-derived basic fibroblast growth factor (bFGF) promotes heme oxygenase-1 (HO-1), which reduces allodynia via its anti-inflammatory properties. To mimic vein wrapping, we developed a collagen sheet impregnated with bFGF. Chronic constriction injury (CCI) was induced in male Wistar rats as a model of sciatic nerve injury, and the rats were divided into three groups: (i) untreated after CCI surgery (control group), (ii) treated with a collagen sheet wrap impregnated with phosphate-buffered saline (PBS/CS group), and (iii) treated with a collagen sheet wrap impregnated with bFGF (bFGF/CS group). Pain behavior (von Frey test) was evaluated on postoperative days (PODs) 1, 5, 7, and 14. Quantitative polymerase chain reaction was conducted on sciatic nerve RNA to quantify HO-1 gene, Hmox1, expression. Enzyme-linked immunosorbent assay were used to determine HO-1 protein levels on POD 1. von Frey testing showed significantly greater pain hypersensitivity in the control and PBS/CS groups than the bFGF/CS group. In the bFGF/CS group, Hmox1 messenger RNA and HO-1 protein levels were significantly increased in the sciatic nerve compared with the control and PBS/CS groups on PODs 1 and 5 and POD 1, respectively. The bFGF/CS group showed decreased allodynia and HO-1 induction, as observed with vein wrapping. Therefore, local application of bFGF may be an alternative treatment strategy for compressive neuropathy and peripheral nerve trauma in clinical settings. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2258-2263, 2019.


Assuntos
Fator 2 de Crescimento de Fibroblastos/administração & dosagem , Hiperalgesia/terapia , Traumatismos dos Nervos Periféricos/terapia , Neuropatia Ciática/terapia , Animais , Colágeno , Portadores de Fármacos , Avaliação Pré-Clínica de Medicamentos , Heme Oxigenase (Desciclizante)/metabolismo , Distribuição Aleatória , Ratos , Nervo Isquiático/metabolismo , Suínos
11.
Arch Orthop Trauma Surg ; 139(7): 1021-1023, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31011794

RESUMO

Nerve injuries, mostly to the median nerve, are common following distal radius fractures. Ulnar nerve injuries are rarely encountered, with only few case reports of motor or motor and sensory loss described in the literature. In this paper, we report two consecutive cases of young patients with a distal radius fracture and a pure sensory ulnar neuropathy. Both patients had a radially displaced fracture and presented with sensory loss and paresthesia in the distribution of the dorsal cutaneous branch of the ulnar nerve (DCBUN), which resolved after fracture reduction. We believe this clinical scenario is the result of traction or compressive neuropraxia of the DCBUN in the subcutaneous tissue around the ulnar styloid-a neurologic injury which had not yet been described for distal radius fractures.


Assuntos
Redução Fechada/métodos , Fratura-Luxação , Traumatismos dos Nervos Periféricos , Fraturas do Rádio , Transtornos das Sensações , Nervo Ulnar/lesões , Punho/diagnóstico por imagem , Adulto , Fratura-Luxação/complicações , Fratura-Luxação/diagnóstico , Fratura-Luxação/fisiopatologia , Fratura-Luxação/cirurgia , Fixação de Fratura/métodos , Humanos , Masculino , Exame Neurológico , Parestesia/diagnóstico , Parestesia/etiologia , Traumatismos dos Nervos Periféricos/diagnóstico , Traumatismos dos Nervos Periféricos/etiologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Traumatismos dos Nervos Periféricos/terapia , Radiografia/métodos , Fraturas do Rádio/complicações , Fraturas do Rádio/diagnóstico , Fraturas do Rádio/fisiopatologia , Fraturas do Rádio/cirurgia , Transtornos das Sensações/diagnóstico , Transtornos das Sensações/etiologia , Pele/inervação , Tato , Resultado do Tratamento
12.
J Am Acad Orthop Surg ; 27(19): 717-725, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30939566

RESUMO

Tardy ulnar nerve palsy is a chronic clinical condition characterized by a delayed onset ulnar neuropathy after an injury to the elbow. Typically, tardy ulnar nerve palsy occurs as a consequence of nonunion of pediatric lateral condyle fractures at the elbow, which eventually lead to a cubitus valgus deformity. While the child grows, the deformity worsens and the ulnar nerve is gradually stretched until classic symptoms of ulnar nerve neuropathy appear. Other childhood elbow trauma has also been associated with tardy ulnar nerve palsy, including supracondylar fractures resulting in cubitus varus, fractures of the medial condyle and of the olecranon, as well as radial head or Monteggia fractures/dislocation, with or without deformity. The clinical assessment includes obtaining a complete history, physical examination, nerve conduction tests, and elbow imaging studies. Treatment consists of ulnar nerve decompression, with or without corrective osteotomy, with overall successful results usually achieved.


Assuntos
Traumatismos do Braço/complicações , Cotovelo/lesões , Fraturas Ósseas/complicações , Traumatismos dos Nervos Periféricos/terapia , Síndromes de Compressão do Nervo Ulnar/terapia , Nervo Ulnar/lesões , Neuropatias Ulnares/terapia , Doença Crônica , Humanos , Traumatismos dos Nervos Periféricos/classificação , Traumatismos dos Nervos Periféricos/diagnóstico , Traumatismos dos Nervos Periféricos/etiologia , Fatores de Tempo , Nervo Ulnar/cirurgia , Síndromes de Compressão do Nervo Ulnar/classificação , Síndromes de Compressão do Nervo Ulnar/diagnóstico , Síndromes de Compressão do Nervo Ulnar/etiologia , Neuropatias Ulnares/classificação , Neuropatias Ulnares/diagnóstico , Neuropatias Ulnares/etiologia
13.
Gene ; 710: 17-23, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-30849542

RESUMO

Mesenchymal stem cells (MSCs) have considerable translational potential in a wide variety of clinical disciplines and are the cellular foundation of individualized treatments of auto-immune, cardiac, neurologic and musculoskeletal diseases and disorders. While the cellular mechanisms by which MSCs exert their biological effects remain to be ascertained, it has been hypothesized that MSCs are supportive of local tissue repair through secretion of essential growth factors. Therapeutic applications of MSCs in peripheral nerve repair have recently been reported. This review focuses on how MSCs can promote nerve regeneration by conversion into Schwann-like cells, and discusses differentiation methods including delivery and dosing of naive or differentiated MSCs, as well as in vitro and in vivo outcomes. While MSC-based therapies for nerve repair are still in early stages of development, current progress in the field provides encouragement that MSCs may have utility in the treatment of patients with peripheral nerve injury.


Assuntos
Células-Tronco Mesenquimais/citologia , Traumatismos dos Nervos Periféricos/terapia , Células de Schwann/citologia , Animais , Diferenciação Celular , Humanos , Regeneração Nervosa , Cicatrização
14.
Ugeskr Laeger ; 181(8)2019 Feb 18.
Artigo em Dinamarquês | MEDLINE | ID: mdl-30821244

RESUMO

Peripheral nerve injury can result in significant morbidity. The gold-standard treatment is currently end-to-end suture and is possible by mobilisation of nerve ends in cases with segmental nerve loss up to 1 cm. In cases of defects above 1 cm nerve autograft is the gold-standard treatment. To avoid donor site morbidity alternative procedures can be used, including conduits, nerve transfers and end-to-side suture. The purpose of this review is to create an overview of the currently available treatments of peripheral nerve injury and the clinical management of patients.


Assuntos
Traumatismos dos Nervos Periféricos , Humanos , Procedimentos Neurocirúrgicos , Traumatismos dos Nervos Periféricos/terapia , Transplante Autólogo
15.
Life Sci ; 221: 99-108, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30735735

RESUMO

Peripheral nerve injury (PNI) is a common life-changing disability of peripheral nervous system with significant socioeconomic consequences. Conventional therapeutic approaches for PNI have several drawbacks such as need to autologous nerve scarifying, surplus surgery, and difficult accessibility to donor nerve; therefore, other therapeutic strategies such as mesenchymal stem cells (MSCs) therapy are getting more interesting. MSCs have been proved to be safe and efficient in numerous degenerative diseases of central and peripheral nervous systems. In this paper, we review novel biotechnological advancements in treating PNI using MSCs.


Assuntos
Transplante de Células-Tronco Mesenquimais/métodos , Traumatismos dos Nervos Periféricos/terapia , Animais , Humanos , Células-Tronco Mesenquimais/fisiologia , Regeneração Nervosa/fisiologia
16.
Neuromodulation ; 22(5): 509-518, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30786105

RESUMO

OBJECTIVES: We aimed to investigate if different protocols of electrical stimulation following nerve injury might improve neuropathic pain outcomes and modify associated plastic changes at the spinal cord level. MATERIALS AND METHODS: Adult rats were subjected to sciatic nerve transection and repair, and distributed in four groups: untreated (SNTR, n = 12), repeated acute electrical stimulation (rAES, 50 Hz, one hour, n = 12), chronic electrical stimulation (CES, 50 Hz, one hour, n = 12), and increasing-frequency chronic electrical stimulation (iCES, one hour, n = 12) delivered during two weeks following the lesion. The threshold of nociceptive withdrawal to mechanical stimuli was evaluated by means of a Von Frey algesimeter during three weeks postlesion. Spinal cord samples were processed by immunohistochemistry for labeling glial cells, adrenergic receptors, K+ -Cl- cotransporter 2 (KCC2) and GABA. RESULTS: Acute electrical stimulation (50 Hz, one hour) delivered at 3, 7, and 14 days induced an immediate increase of mechanical pain threshold that disappeared after a few days. Chronic electrical stimulation given daily reduced mechanical hyperalgesia until the end of follow-up, being more sustained with the iCES than with constant 50 Hz stimulation (CES). Chronic stimulation protocols restored the expression of ß2 adrenergic receptor and of KCC2 in the dorsal horn, which were significantly reduced by nerve injury. These treatments decreased also the activation of microglia and astrocytes in the dorsal horn. CONCLUSION: Daily electrical stimulation, especially if frequency-patterned, was effective in ameliorating hyperalgesia after nerve injury, and partially preventing the proinflammatory and hyperalgesic changes in the dorsal horn associated to neuropathic pain.


Assuntos
Terapia por Estimulação Elétrica/métodos , Hiperalgesia/terapia , Neuralgia/terapia , Traumatismos dos Nervos Periféricos/terapia , Células do Corno Posterior , Animais , Feminino , Hiperalgesia/etiologia , Hiperalgesia/metabolismo , Neuralgia/etiologia , Neuralgia/metabolismo , Traumatismos dos Nervos Periféricos/complicações , Traumatismos dos Nervos Periféricos/metabolismo , Células do Corno Posterior/metabolismo , Ratos , Ratos Sprague-Dawley
17.
PLoS One ; 14(1): e0210211, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30625210

RESUMO

The effects of low-level laser therapy (LLLT) and natural latex protein (F1, Hevea brasiliensis) were evaluated on crush-type injuries (15kg) to the sciatic nerve in the expressions of nerve growth factor (NGF) and vascular endothelium growth factor (VEGF) and ultrastructural morphology to associate with previous morphometric data using the same protocol of injury and treatment. Thirty-six male rats were allocated into six experimental groups (n = 6): 1-Control; 2-Exposed nerve; 3-Injured nerve; 4-LLLT (15J/cm2, 780nm, 30mW, Continuous Wave) treated injured nerve; 5-F1 (0,1mg) treated injured nerve; and 6-LLLT&F1 treated injured nerve. Four or eight weeks after, sciatic nerve samples were processed for analysis. NGF expression were higher (p<0.05) four weeks after in all injured groups in comparison to Control (Med:0.8; Q1:0; Q3:55.5%area). Among them, the Injured (Med:70.7; Q1:64.4; Q3:77.5%area) showed the highest expression, and F1 (Med:17.3; Q1:14.1; Q3:21.7%area) had the lowest. At week 8, NGF expressions decreased in the injured groups. VEGF was expressed in all groups; its higher expression was observed in the injured groups 4 weeks after (Injured. Med:29.5; F1. Med:17.7 and LLLT&F1. Med:19.4%area). At week 8, a general reduction of VEGF expression was noted, remaining higher in F1 (Med:35.1; Q1.30.6; Q3.39.6%area) and LLLT&F1 (Med:18.5; Q1:16; Q3:25%area). Ultrastructural morphology revealed improvements in the treated groups; 4 weeks after, the F1 group presented greater quantity and diameter of the nerve fibers uniformly distributed. Eight weeks after, the F1 and LLLT&F1 showed similar characteristics to the non-injured groups. In summary, these results and our previous studies indicated that F1 and LLLT may favorably influence the healing of nerve crush injury. Four weeks after nerve injury F1 group showed the best results suggesting recovery acceleration; at 8th week F1 and LLLT&F1 groups presented better features and higher vascularization that could be associated with VEGF maintenance.


Assuntos
Hevea/química , Terapia com Luz de Baixa Intensidade , Traumatismos dos Nervos Periféricos/terapia , Proteínas de Plantas/administração & dosagem , Nervo Isquiático/lesões , Animais , Lesões por Esmagamento/complicações , Modelos Animais de Doenças , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Látex/química , Masculino , Microscopia Eletrônica de Transmissão , Regeneração Nervosa/efeitos dos fármacos , Regeneração Nervosa/efeitos da radiação , Traumatismos dos Nervos Periféricos/etiologia , Proteínas de Plantas/isolamento & purificação , Ratos , Ratos Wistar , Recuperação de Função Fisiológica , Nervo Isquiático/fisiologia , Nervo Isquiático/ultraestrutura , Cicatrização/efeitos dos fármacos , Cicatrização/efeitos da radiação
18.
Cell Mol Neurobiol ; 39(3): 341-353, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30684112

RESUMO

The present study aimed to investigate the efficacy of transplantation of bone marrow neural tissue-committed stem cell-derived sensory neuron-like cells for the repair of peripheral nerve sensory impairments in rats. Bone marrow was isolated and cultured to obtain the neural tissue-committed stem cells (NTCSCs), and the differentiation of these cells into sensory neuron-like cells was induced. Bone marrow mesenchymal stem cells (BMSCs), bone marrow NTCSCs, and bone marrow NTCSC-derived sensory neurons (NTCSC-SNs) were transplanted by microinjection into the L4 and L5 dorsal root ganglions (DRGs) in an animal model of sensory defect. On the 2nd, 4th, 8th, and 12th week after the transplantation, the effects of the three types of stem cells on the repair of the sensory functional defect were analyzed via behavioral observation, sensory function evaluation, electrophysiological examination of the sciatic nerve, and morphological observation of the DRGs. The results revealed that the transplanted BMSCs, NTCSCs, and NTCSC-SNs were all able to repair the sensory nerves. In addition, the effect of the NTCSC-SNs was significantly better than that of the other two types of stem cells. The general posture and gait of the animals in the sensory defect model exhibited evident improvement over time. Plantar temperature sensitivity and pain sensitivity gradually recovered, and the sensation latency was reduced, with faster sensory nerve conduction velocity. Transplantation of NTCSC-SNs can improve the repair of peripheral nerve sensory defects in rats.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Regeneração Nervosa , Tecido Nervoso/citologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Traumatismos dos Nervos Periféricos/terapia , Células Receptoras Sensoriais/transplante , Potenciais de Ação , Animais , Comportamento Animal , Separação Celular , Forma Celular , Sobrevivência Celular , Modelos Animais de Doenças , Masculino , Proteínas do Tecido Nervoso/metabolismo , Condução Nervosa , Neurônios/citologia , Traumatismos dos Nervos Periféricos/patologia , Ratos Sprague-Dawley , Células Receptoras Sensoriais/citologia , Esferoides Celulares/citologia
19.
J Mol Neurosci ; 67(1): 48-61, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30484060

RESUMO

Motor and sensory recovery following critical size peripheral nerve defects is often incomplete. Although nerve grafting has been proposed as the gold standard, it is associated with several disadvantages. Here we report a novel approach to peripheral nerve repair using Human Unrestricted Somatic Stem Cells (USSC) delivered through an electrospun neural guidance conduit. Conduits were produced from PCL and gelatin blend. Several in vitro methods were utilized to investigate the conduit's physicochemical and biological characteristics. Nerve regeneration was studied across a 10-mm sciatic nerve gap in Wistar rats. For functional analysis, the conduits were seeded with 3 × 104 USSCs and implanted into a 10-mm sciatic nerve defect. After 14 weeks, the results of functional recovery analysis and histopathological examinations showed that animals implanted with USSC containing conduits exhibited improved functional and histopathological recovery which was more close to the autograft group compared to other groups. Our results support the potential applicability of USSCs to treat peripheral nerve injury in the clinic.


Assuntos
Regeneração Tecidual Guiada/métodos , Nanofibras/química , Regeneração Nervosa , Traumatismos dos Nervos Periféricos/terapia , Transplante de Células-Tronco/métodos , Animais , Células Cultivadas , Masculino , Ratos , Ratos Wistar , Nervo Isquiático/lesões , Nervo Isquiático/fisiologia , Tecidos Suporte/química
20.
Neurosci Res ; 145: 22-29, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30125610

RESUMO

Electrical stimulation could enhance nerve regeneration and functional recovery. The objective of this study was to evaluate the regenerative effects of implanted electrodes with different contacts in resected sciatic nerve. Sciatic nerve resection and microsurgical repair models were established and randomly divided into four groups (point contact, 1/4 circle contact; whole-circle contact; no electrodes as control). Electrical stimulation was performed and electrophysiological, morphological and histological exams (of the sciatic nerve and muscle) were conducted at 4 and 10 weeks post-implantation. Point and 1/4 circle contact groups showed significantly higher scores in the sciatic functional index (SFI), increased amplitude of compound muscle action potential (AMP) and motor nerve conduction velocity (MNCV) compared to the control group at both 4 and 10 weeks post-implantation. Point and 1/4 circle contact morphologically promoted sciatic nerve regeneration and reduced muscular atrophy with less mechanical injury to the nerve trunk observed compared with the whole-circle contact group at both 4 and 10 weeks post-implantation. Electrodes with point and 1/4 circle contacts represented an alternatively portable and effective method of electrical stimulation to facilitate injured sciatic nerve regeneration and reduce subsequent muscular atrophy, which might offer a promising approach for treating peripheral nerve injuries.


Assuntos
Terapia por Estimulação Elétrica/métodos , Eletrodos Implantados , Traumatismos dos Nervos Periféricos/terapia , Recuperação de Função Fisiológica , Nervo Isquiático/lesões , Animais , Masculino , Músculo Esquelético/inervação , Regeneração Nervosa/fisiologia , Traumatismos dos Nervos Periféricos/patologia , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/patologia , Nervo Isquiático/ultraestrutura
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