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1.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 3823-3826, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018834

RESUMO

the purpose of targeted muscle reinnervation (TMR) surgery is to provide more electromyography information for prosthetic control by reconstructing the deconstructed structure between the distal nerve and the stump muscle. Functional electrical stimulation (FES) of denervated muscles or proximal nerve stump after peripheral nerve surgery can effectively promote nerve regeneration and muscle function recovery. This pilot divided SD adult male rats into normal control group, denervation group, TMR group, and FES group according to whether they received TMR surgery and whether they received FES after surgery. The results showed that low-frequency electrical stimulation treatment could effectively promote transplanted nerve regeneration and significantly enhances motor function of target muscles.Clinical Relevance-This experiment successfully established TMR rat models, and explored the recovery of injured neuromuscular function by using electrodes implanted intramuscularly and analyzing myoelectric signals, and the use of low-frequency electrical stimulation treatment had a positive effect on the regeneration of the transplanted nerve.


Assuntos
Fenômenos Fisiológicos Musculoesqueléticos , Procedimentos Cirúrgicos Reconstrutivos , Animais , Estimulação Elétrica , Masculino , Regeneração Nervosa , Procedimentos Neurocirúrgicos , Ratos
2.
PLoS One ; 15(10): e0238578, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33001981

RESUMO

The spiral ganglion neurons constitute the primary connection between auditory hair cells and the brain. The spiral ganglion afferent fibers and their synapse with hair cells do not regenerate to any significant degree in adult mammalian ears after damage. We have investigated gene expression changes after kainate-induced disruption of the synapses in a neonatal cochlear explant model in which peripheral fibers and the afferent synapse do regenerate. We compared gene expression early after damage, during regeneration of the fibers and synapses, and after completion of in vitro regeneration. These analyses revealed a total of 2.5% differentially regulated transcripts (588 out of 24,000) based on a threshold of p<0.005. Inflammatory response genes as well as genes involved in regeneration of neural circuits were upregulated in the spiral ganglion neurons and organ of Corti, where the hair cells reside. Prominent genes upregulated at several time points included genes with roles in neurogenesis (Elavl4 and Sox21), neural outgrowth (Ntrk3 and Ppp1r1c), axonal guidance (Rgmb and Sema7a), synaptogenesis (Nlgn2 and Psd2), and synaptic vesicular function (Syt8 and Syn1). Immunohistochemical and in situ hybridization analysis of genes that had not previously been described in the cochlea confirmed their cochlear expression. The time course of expression of these genes suggests that kainate treatment resulted in a two-phase response in spiral ganglion neurons: an acute response consistent with inflammation, followed by an upregulation of neural regeneration genes. Identification of the genes activated during regeneration of these fibers suggests candidates that could be targeted to enhance regeneration in adult ears.


Assuntos
Células Ciliadas Auditivas/fisiologia , Regeneração Nervosa/genética , Regeneração Nervosa/fisiologia , Neurônios Aferentes/fisiologia , Animais , Animais Recém-Nascidos , Expressão Gênica/efeitos dos fármacos , Células Ciliadas Auditivas/efeitos dos fármacos , Inflamação/genética , Inflamação/fisiopatologia , Ácido Caínico/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Modelos Neurológicos , Neurogênese/genética , Neurogênese/fisiologia , Gânglio Espiral da Cóclea/citologia , Gânglio Espiral da Cóclea/fisiologia , Sinapses/fisiologia , Técnicas de Cultura de Tecidos
3.
Nat Commun ; 11(1): 4504, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32908131

RESUMO

The strategies concerning modification of the complex immune pathological inflammatory environment during acute spinal cord injury remain oversimplified and superficial. Inspired by the acidic microenvironment at acute injury sites, a functional pH-responsive immunoregulation-assisted neural regeneration strategy was constructed. With the capability of directly responding to the acidic microenvironment at focal areas followed by triggered release of the IL-4 plasmid-loaded liposomes within a few hours to suppress the release of inflammatory cytokines and promote neural differentiation of mesenchymal stem cells in vitro, the microenvironment-responsive immunoregulatory electrospun fibers were implanted into acute spinal cord injury rats. Together with sustained release of nerve growth factor (NGF) achieved by microsol core-shell structure, the immunological fiber scaffolds were revealed to bring significantly shifted immune cells subtype to down-regulate the acute inflammation response, reduce scar tissue formation, promote angiogenesis as well as neural differentiation at the injury site, and enhance functional recovery in vivo. Overall, this strategy provided a delivery system through microenvironment-responsive immunological regulation effect so as to break through the current dilemma from the contradiction between immune response and nerve regeneration, providing an alternative for the treatment of acute spinal cord injury.


Assuntos
Microambiente Celular/imunologia , Sistemas de Liberação de Medicamentos/instrumentação , Fator de Crescimento Neural/administração & dosagem , Regeneração Nervosa/efeitos dos fármacos , Traumatismos da Medula Espinal/terapia , Tecidos Suporte , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Preparações de Ação Retardada/administração & dosagem , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Interleucina-4/administração & dosagem , Lipossomos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/fisiologia , Fator de Crescimento Neural/farmacocinética , Regeneração Nervosa/imunologia , Ratos , Recuperação de Função Fisiológica/imunologia , Medula Espinal/citologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/imunologia , Traumatismos da Medula Espinal/imunologia
4.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(4): 500-507, 2020 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-32985164

RESUMO

Different from neurons in the peripheral nervous system, mature neurons in the mammalian central nervous system often fail to regenerate after injury. Recent studies have found that calcium transduction, injury signaling, mitochondrial transportation, cytoskeletal remodeling and protein synthesis play essential roles in axon regeneration. Firstly, axon injury increases the intracellular concentration of calcium, and initiates the injury signaling pathways including cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) and dual leucine kinase (DLK), which are found to promote axon regeneration in multiple animal injury models. The second step for axonal regrowth is to rebuild growth cones. Overexpressing proteins that promote dynamics of microtubules and actin filaments is beneficial for the reassembly of cytoskeletons and initiation of new growth cones. Thirdly, mitochondria, the power factory for cells, also play important roles in growth cone formation and axonal extension. The last but not the least important step is the regulation of gene transcription and protein translation to sustain the regrowth of axons. This review summarizes important findings revealing the functions and mechanisms of these biological progresses.


Assuntos
Axônios , Regeneração Nervosa , Neurologia , Pesquisa , Animais , Axônios/fisiologia , Cones de Crescimento/fisiologia , Modelos Animais , Regeneração Nervosa/fisiologia , Neurologia/tendências , Pesquisa/tendências
5.
Nat Commun ; 11(1): 4891, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32994417

RESUMO

Peripheral sensory neurons regenerate their axon after nerve injury to enable functional recovery. Intrinsic mechanisms operating in sensory neurons are known to regulate nerve repair, but whether satellite glial cells (SGC), which completely envelop the neuronal soma, contribute to nerve regeneration remains unexplored. Using a single cell RNAseq approach, we reveal that SGC are distinct from Schwann cells and share similarities with astrocytes. Nerve injury elicits changes in the expression of genes related to fatty acid synthesis and peroxisome proliferator-activated receptor (PPARα) signaling. Conditional deletion of fatty acid synthase (Fasn) in SGC impairs axon regeneration. The PPARα agonist fenofibrate rescues the impaired axon regeneration in mice lacking Fasn in SGC. These results indicate that PPARα activity downstream of FASN in SGC contributes to promote axon regeneration in adult peripheral nerves and highlight that the sensory neuron and its surrounding glial coat form a functional unit that orchestrates nerve repair.


Assuntos
Regeneração Nervosa , Neuroglia/citologia , Células Receptoras Sensoriais/citologia , Animais , Axônios/fisiologia , Proliferação de Células , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neuroglia/metabolismo , PPAR alfa/genética , PPAR alfa/metabolismo , Traumatismos dos Nervos Periféricos/genética , Traumatismos dos Nervos Periféricos/metabolismo , Traumatismos dos Nervos Periféricos/fisiopatologia , Nervos Periféricos/crescimento & desenvolvimento , Nervos Periféricos/metabolismo , Nervos Periféricos/fisiopatologia , Células Receptoras Sensoriais/metabolismo , Transdução de Sinais
7.
Plast Reconstr Surg ; 146(2): 250-254, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32740571

RESUMO

The concept of sensate autologous breast reconstruction is not novel, and prior literature has focused mainly on sensate abdominally based breast reconstruction. The goal of this article is to present the authors' results with a novel technique performing sensate implant-based reconstruction. A database was prospectively maintained for patients who underwent implant-based sensate breast reconstruction. The anterior branch of the lateral fourth intercostal is identified and preserved during the mastectomy by the breast surgeon. A processed nerve allograft is used as an interpositional graft connecting the donor nerve to the targeted nipple-areola complex. The sensory recovery process was objectively monitored using a pressure-specified sensory device. Thirteen patients underwent the proposed technique. Eight patients with 15 breasts were monitored for sensory recovery. For sensory measurement, the nipple had a mean threshold of 67.33 ± 34.48 g/nm. The upper inner (29 ± 26.75 g/nm) and upper outer (46.82 ± 32.72 g/nm) nipple-areola complex quadrants demonstrated better scores during the moving test compared with the static test. Mean time between the test and surgery was 4.18 ± 2.3 months, and mean time between the second test and surgery was 10.59 ± 3.57 months. Threshold improvements were documented after the second test for all nipple-areola complex areas evaluated. This is the first study to report on early results obtained after performing sensate implant-based breast reconstruction. More studies are required to determine the long-term outcomes and impact on quality of life and to assess whether patient or breast characteristics impact the success of this procedure.


Assuntos
Implantes de Mama , Mamoplastia/métodos , Regeneração Nervosa/fisiologia , Transferência de Nervo/métodos , Mamilos/cirurgia , Recuperação de Função Fisiológica , Sensação/fisiologia , Adulto , Neoplasias da Mama/cirurgia , Feminino , Seguimentos , Humanos , Mastectomia Subcutânea/métodos , Mamilos/inervação , Estudos Prospectivos , Qualidade de Vida , Fatores de Tempo
8.
PLoS Genet ; 16(8): e1008942, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32764744

RESUMO

To remodel functional neuronal connectivity, neurons often alter dendrite arbors through elimination and subsequent regeneration of dendritic branches. However, the intrinsic mechanisms underlying this developmentally programmed dendrite regeneration and whether it shares common machinery with injury-induced regeneration remain largely unknown. Drosophila class IV dendrite arborization (C4da) sensory neurons regenerate adult-specific dendrites after eliminating larval dendrites during metamorphosis. Here we show that the microRNA miR-87 is a critical regulator of dendrite regeneration in Drosophila. miR-87 knockout impairs dendrite regeneration after developmentally-programmed pruning, whereas miR-87 overexpression in C4da neurons leads to precocious initiation of dendrite regeneration. Genetic analyses indicate that the transcriptional repressor Tramtrack69 (Ttk69) is a functional target for miR-87-mediated repression as ttk69 expression is increased in miR-87 knockout neurons and reducing ttk69 expression restores dendrite regeneration to mutants lacking miR-87 function. We further show that miR-87 is required for dendrite regeneration after acute injury in the larval stage, providing a mechanistic link between developmentally programmed and injury-induced dendrite regeneration. These findings thus indicate that miR-87 promotes dendrite regrowth during regeneration at least in part through suppressing Ttk69 in Drosophila sensory neurons and suggest that developmental and injury-induced dendrite regeneration share a common intrinsic mechanism to reactivate dendrite growth.


Assuntos
Proteínas de Drosophila/genética , Metamorfose Biológica/genética , MicroRNAs/genética , Regeneração Nervosa/genética , Proteínas Repressoras/genética , Animais , Dendritos/genética , Dendritos/fisiologia , Drosophila melanogaster/genética , Regulação da Expressão Gênica no Desenvolvimento , Larva/genética , Larva/crescimento & desenvolvimento , Células Receptoras Sensoriais/metabolismo
9.
PLoS One ; 15(8): e0237231, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32853250

RESUMO

In this study, we examined the effect of differing gap lengths on regeneration of transected recurrent laryngeal nerves using silicon tubes containing type I collagen gel and the ability of this regeneration to result in restoration of vocal fold movements in rats. We simulated nerve gaps in Sprague-Dawley rats by transecting the left recurrent laryngeal nerves and bridged the nerve stumps using silicon tubes containing type 1 collagen gel. Three experimental groups, in which the gap lengths between the stumps were 1, 3, or 5 mm, were compared with a control group in which the nerve was transected but was not bridged. After surgery, we observed vocal fold movements over time with a laryngoscope. At week 15, we assessed the extent of nerve regeneration in the tube, histologically and electrophysiologically. We also assessed the degree of atrophy of the thyroarytenoid muscle (T/U ratio). Restoration of vocal fold movements was observed in 9 rats in the 1-mm group, in 6 rats in the 3-mm group, and in 3 rats in the 5-mm group. However, in most rats, restoration was temporary, with only one rat demonstrating continued vocal fold movements at week 15. In electromyograph, evoked potentials were observed in rats in the 1-mm and 3-mm groups. Regenerated tissue in the tube was thickest in the 1-mm group, followed by the 3-mm and 5-mm groups. The regenerated tissue showed the presence of myelinated and unmyelinated nerve fibers. In assessment of thyroarytenoid muscle atrophy, the T/U ratio was highest in the 1-mm group, followed by the 3-mm and 5-mm groups. We successfully regenerated the nerves and produced a rat model of recurrent laryngeal nerve regeneration that demonstrated temporary recovery of vocal fold movements. This rat model could be useful for assessing novel treatments developing in the future.


Assuntos
Colágeno/uso terapêutico , Regeneração Nervosa , Traumatismos do Nervo Laríngeo Recorrente/terapia , Nervo Laríngeo Recorrente/fisiopatologia , Animais , Materiais Biocompatíveis/química , Colágeno/administração & dosagem , Modelos Animais de Doenças , Géis/administração & dosagem , Géis/uso terapêutico , Masculino , Regeneração Nervosa/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Nervo Laríngeo Recorrente/fisiologia , Traumatismos do Nervo Laríngeo Recorrente/fisiopatologia , Silício/química
10.
Acta Cir Bras ; 35(7): e202000702, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32813758

RESUMO

Purpose To evaluate the normality pattern in functional tests of peripheral nerves. Methods Sixty female and sixty male Wistar rats were submitted to vibrissae movement and nictitating reflex for facial nerve; grooming test and grasping test for brachial plexus; and walking tracking test and horizontal ladder test for lumbar plexus. The tests were performed separately, with an interval of seven days between each. Results All animals showed the best score in vibrissae movement, nictitating reflex, grooming test, and horizontal ladder test. The best score was acquired for the first time in more than 90% of animals. The mean of strength on the grasping test was 133.46±12.08g for the right and 121.74±8.73g for the left anterior paw. There was a difference between the right and left sides. There was no difference between the groups according to sex. There is no statistical difference comparing all functional indexes between sex, independent of the side analyzed. The peroneal functional index showed higher levels than the sciatic and tibial functional index on both sides and sex. Conclusions The behavioral and functional assessment of peripheral nerve regeneration are low-cost, easy to perform, and reliable tests. However, they need to be performed by experienced researchers to avoid misinterpretation.


Assuntos
Traumatismos dos Nervos Periféricos , Animais , Plexo Braquial , Nervo Facial , Feminino , Masculino , Regeneração Nervosa , Ratos , Ratos Wistar , Nervo Isquiático
11.
Adv Clin Exp Med ; 29(7): 819-824, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32735402

RESUMO

BACKGROUND: Conservative treatment, such as electrical stimulation and steroid injection, have been employed in an attempt to improve symptoms after peripheral nerve injury, without significant success. Although non-invasive and safe extracorporeal shockwave therapy (ESWT) can be a practical alternative, the therapeutic effects of ESWT on peripheral nerve remyelination has not been established. OBJECTIVES: To investigate the effects of ESWT on peripheral nerve remyelination and gait function for 5 weeks in a sciatic nerve crush model. MATERIAL AND METHODS: In total, we divided 97 rats into 5 groups: group 1 - a healthy negative control group; group 2 - 3 weeks after sciatic nerve crush and 3 sessions of ESWT; group 3 - 5 weeks after crush injury with 3 sessions of ESWT; group 4 - 3 weeks after crush injury with no ESWT; and group 5 - 5 weeks after crush injury with no ESWT. The focused ESWT was applied to the unilateral sciatic nerve injury site. One session consisted of 1,500 stimuli, and the session were performed at intervals of 1 week. RESULTS: The degree of myelination and expression of myelin basic protein at the distal part of the injured sciatic nerve tended to increase in the ESWT groups compared with the no-ESWT groups 3 and 5 weeks after crush injury. Regarding the functional gait recovery, the print width and area of the injured leg in the ESWT groups was significantly larger than that in the no-ESWT groups 3 and 5 weeks after crush injury. CONCLUSIONS: The ESWT may enhance peripheral nerve remyelination and gait function in a nerve crush model. Long-term follow-up after ESWT and investigation of molecular mechanisms will be needed to confirm these therapeutic effects.


Assuntos
Tratamento por Ondas de Choque Extracorpóreas , Remielinização , Animais , Marcha , Compressão Nervosa , Regeneração Nervosa , Ratos , Recuperação de Função Fisiológica , Nervo Isquiático
12.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(1): 82-89, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32621408

RESUMO

The intrinsic regrowth ability of injured neurons is essential for axon regeneration and functional recovery. Recently, numerous intrinsic pathways that regulate axon regeneration have been discovered, among which the mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway are arguably the best characterized examples. MAPK signaling pathway is involved in multiple processes including sensing injury signals, initiating and promoting axonal regrowth through regulating cytoskeleton dynamics and protein synthesis. The PI3K/Akt signaling pathway regulates axon regeneration mainly through gene transcription and translation. Combinatory manipulation of multiple regeneration-promoting signals can further improve the extend of axonal regrowth. This paper summarizes current progresses on axon regeneration studies in various organisms and discuss their potentials in promoting functional recovery in vivo.


Assuntos
Axônios , Regeneração Nervosa , Transdução de Sinais , Axônios/fisiologia , Neurônios , Fosfatidilinositol 3-Quinases , Regeneração
13.
Neuron ; 107(5): 854-863.e6, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32640191

RESUMO

The xbp-1 mRNA encodes the XBP-1 transcription factor, a critical part of the unfolded protein response. Here we report that an RNA fragment produced from xbp-1 mRNA cleavage is a biologically active non-coding RNA (ncRNA) essential for axon regeneration in Caenorhabditis elegans. We show that the xbp-1 ncRNA acts independently of the protein-coding function of the xbp-1 transcript as part of a dual output xbp-1 mRNA stress response axis. Structural analysis indicates that the function of the xbp-1 ncRNA depends on a single RNA stem; this stem forms only in the cleaved xbp-1 ncRNA fragment. Disruption of this stem abolishes the non-coding, but not the coding, function of the endogenous xbp-1 transcript. Thus, cleavage of the xbp-1 mRNA bifurcates it into a coding and a non-coding pathway; modulation of the two pathways may allow neurons to fine-tune their response to injury and other stresses.


Assuntos
Proteínas de Caenorhabditis elegans/genética , Proteínas de Transporte/genética , Regeneração Nervosa/genética , RNA Mensageiro/genética , RNA não Traduzido/genética , Animais , Caenorhabditis elegans , Resposta a Proteínas não Dobradas/genética
14.
Science ; 368(6498): 1428-1429, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32587008
15.
J Vis Exp ; (159)2020 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-32510487

RESUMO

The principal cells in the peripheral nervous system are the Schwann cells (SCs) and the fibroblasts. Both these cells distinctly express the sensory and motor phenotypes involved in different patterns of neurotrophic factor gene expression and other biological processes, affecting nerve regeneration. The present study has established a protocol to obtain highly purified rat sensory and motor SCs and fibroblasts more rapidly. The ventral root (motor nerve) and the dorsal root (sensory nerve) of neonatal rats (7-days-old) were dissociated and the cells were cultured for 4-5 days, followed by isolation of sensory and motor fibroblasts and SCs by combining differential digestion and differential adherence methods sequentially. The results of immunocytochemistry and flow cytometry analyses showed that the purity of the sensory and motor SCs and fibroblasts were >90%. This protocol can be used to obtain a large number of sensory and motor fibroblasts/SCs more rapidly, contributing to the exploration of sensory and motor nerve regeneration.


Assuntos
Separação Celular/métodos , Fibroblastos/citologia , Neurônios Motores/citologia , Células de Schwann/citologia , Células Receptoras Sensoriais/citologia , Animais , Regeneração Nervosa , Fenótipo , Ratos
16.
PLoS One ; 15(6): e0234691, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555658

RESUMO

BACKGROUND: Therapeutic ultrasound (US) is a promising physical therapy modality for peripheral nerve regeneration. However, it is necessary to identify the most effective US parameters and clarify the underlying mechanisms before its clinical application. The intensity of US is one of the most important parameters. However, the optimum intensity for the promotion of peripheral nerve regeneration has yet to be determined. OBJECTIVES: To identify the optimum intensity of US necessary for the promotion of peripheral nerve regeneration after crush injuries in rats and to clarify the underlying mechanisms of US by mRNA expression analysis. METHODS: We inflicted sciatic nerve crush injuries on adult Lewis rats and performed ultrasound irradiation using 4 different US intensities: 0 (sham stimulation), 30, 140, and 250 mW/cm2 with frequency (5 days/week) and duration (5 min/day). We evaluated peripheral nerve regeneration by quantitative real-time PCR one week after injury. Histomorphometric analyses and motor function analysis were evaluated 3 weeks after injury. RESULTS: US stimulation enhanced re-myelination as well as sprouting of axons, especially at an intensity of 140 mW/cm2. mRNA expression revealed that US suppressed the expression of the inflammatory cytokines TNF and IL-6 and the axonal growth inhibitors SEMA3A and GSK3ß. CONCLUSIONS: An intensity of 140 mW/cm2 was optimal to support regeneration of the sciatic nerve after a crush injury in rats by, in part, the suppression of pro-inflammatory and nerve growth inhibitor gene expression.


Assuntos
Regulação da Expressão Gênica , Glicogênio Sintase Quinase 3 beta/genética , Regeneração Nervosa , Traumatismos dos Nervos Periféricos/fisiopatologia , Traumatismos dos Nervos Periféricos/terapia , Semaforina-3A/genética , Terapia por Ultrassom , Animais , Citocinas/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Mediadores da Inflamação/metabolismo , Masculino , Bainha de Mielina/metabolismo , Compressão Nervosa , Regeneração Nervosa/genética , Traumatismos dos Nervos Periféricos/diagnóstico por imagem , Traumatismos dos Nervos Periféricos/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Endogâmicos Lew , Nervo Isquiático/lesões , Nervo Isquiático/patologia , Nervo Isquiático/fisiopatologia , Nervo Isquiático/ultraestrutura , Semaforina-3A/metabolismo
17.
Life Sci ; 256: 117959, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32531375

RESUMO

Resveratrol has the ability to promote functional recovery after sciatic nerve crush injury (SNCI), though the mechanism through which this occurs in not fully understood. Resveratrol can promote autophagy, a key process in Wallerian degeneration; thus, we hypothesized that resveratrol could promote recovery from SNCI by promoting Schwann cell autophagy and acceleration of Wallerian degeneration. Motor function recovery was assessed by calculating Sciatic Function Indexes (SFIs) at days 7, 14, 21, 28 post SNCI. Autophagy and myelin clearance were assessed by microtubule-associated protein light chain 3B (LC3B) and myelin protein zero (MPZ) immunofluorescence and Western blot analysis on the fourth day after SNCI. The autophagy of Schwann cells following resveratrol administration was quantified by immunofluorescence in RSC96 cells. Immunofluorescence and Transmission electron microscopy (TEM) were also used in Resveratrol treated sciatic nerve four days post-SNCI to find LC3B positive areas and typical double membrane structures represent for autophagy. The SNCI+resveratrol (crush+Res) groups recovered faster than the SNCI+vehicles (crush+V) group. On day four, almost all of the myelin had regenerated in the crush+Res rats, while the crush+V group's myelin remained intact and the expression levels of LC3-II/I was the highest. On day 28 post-injury, both the control and crush+Res groups' myelin neurofibers reached peak numbers as did the thickness of the myelin sheath. Both in vitro and in vivo immunofluorescence showed that LC3B was colocalized with Schwann cells. This is the first study to observe that resveratrol can promote recovery from SCNI by accelerating the myelin clearance process by promoting autophagy of Schwann cells.


Assuntos
Autofagia/efeitos dos fármacos , Lesões por Esmagamento/fisiopatologia , Compressão Nervosa , Recuperação de Função Fisiológica/efeitos dos fármacos , Resveratrol/farmacologia , Células de Schwann/patologia , Nervo Isquiático/patologia , Nervo Isquiático/fisiopatologia , Animais , Axônios/efeitos dos fármacos , Axônios/patologia , Lesões por Esmagamento/patologia , Masculino , Proteínas Associadas aos Microtúbulos/metabolismo , Atividade Motora/efeitos dos fármacos , Proteína P0 da Mielina/metabolismo , Bainha de Mielina/efeitos dos fármacos , Bainha de Mielina/metabolismo , Fibras Nervosas/efeitos dos fármacos , Fibras Nervosas/patologia , Regeneração Nervosa/efeitos dos fármacos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Células de Schwann/efeitos dos fármacos , Células de Schwann/metabolismo , Nervo Isquiático/efeitos dos fármacos
18.
Proc Natl Acad Sci U S A ; 117(27): 15955-15966, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32554499

RESUMO

Axon regeneration is regulated by a neuron-intrinsic transcriptional program that is suppressed during development but that can be reactivated following peripheral nerve injury. Here we identify Prom1, which encodes the stem cell marker prominin-1, as a regulator of the axon regeneration program. Prom1 expression is developmentally down-regulated, and the genetic deletion of Prom1 in mice inhibits axon regeneration in dorsal root ganglion (DRG) cultures and in the sciatic nerve, revealing the neuronal role of Prom1 in injury-induced regeneration. Elevating prominin-1 levels in cultured DRG neurons or in mice via adeno-associated virus-mediated gene delivery enhances axon regeneration in vitro and in vivo, allowing outgrowth on an inhibitory substrate. Prom1 overexpression induces the consistent down-regulation of cholesterol metabolism-associated genes and a reduction in cellular cholesterol levels in a Smad pathway-dependent manner, which promotes axonal regrowth. We find that prominin-1 interacts with the type I TGF-ß receptor ALK4, and that they synergistically induce phosphorylation of Smad2. These results suggest that Prom1 and cholesterol metabolism pathways are possible therapeutic targets for the promotion of neural recovery after injury.


Assuntos
Antígeno AC133/metabolismo , Axônios/metabolismo , Colesterol/metabolismo , Regeneração Nervosa/fisiologia , Transdução de Sinais , Células-Tronco/metabolismo , Antígeno AC133/genética , Receptores de Ativinas Tipo I , Animais , Axônios/patologia , Colesterol/genética , Regulação para Baixo , Gânglios Espinais/metabolismo , Deleção de Genes , Regulação da Expressão Gênica , Camundongos , Camundongos Knockout , Neurônios/metabolismo , Traumatismos dos Nervos Periféricos/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Nervo Isquiático
19.
ABCS health sci ; 45: e020016, 02 jun 2020. tab, ilus, graf
Artigo em Inglês | LILACS | ID: biblio-1123701

RESUMO

INTRODUCTION: Different studies have evaluated the effects of electrophysical agents on regeneration after peripheral nerve injury. Among them, the most used in clinical and experimental research is photobiomodulation therapy (PBMT). OBJECTIVE: To analyze the effect of standard energy (16.8 J) of PBMT on peripheral nerve regeneration, applied at different periods after sciatic nerve injury in mice. METHODS: Thirty male Swiss mice were divided into six groups: naive; sham; control; LLLT-01 (660 nm, 16.8 J of total energy emitted in 1 day); LLLT-04 (660 nm, 4.2 J per day, 16.8 J of total energy emitted in 4 days); LLLT-28, (660 nm, 0.6 J per day, 16.8 J of total energy emitted over 28 days). The animals were evaluated using thermal hyperalgesia, Sciatic Functional Index (SFI), and Static Sciatic Index (SSI). Data were obtained at baseline and after 7, 14, 21, and 28 days after surgery. RESULTS: For the SFI and SSI, all groups showed significant differences compared to the control group, and the LLLT-04 group presented the best results among those receiving PBMT. In the assessment of thermal hyperalgesia, there was a significant difference in the 14th day of evaluation in the LLLT-04 group. CONCLUSION: The application of 16.8 J was useful in sciatic nerve regeneration with an improvement of hyperalgesia, with higher efficacy when applied in four days (4.2 J/day).


INTRODUÇÃO: Estudos avaliaram os efeitos de diferentes terapias aplicadas após lesão nervosa periférica, com o intuito de promover a regeneração local. Dentre elas, a mais utilizada em pesquisa clínica e experimental é a terapia de fotobiomodulação (TFBM). OBJETIVO: Analisar o efeito da fotobiomodulação (16,8 J) na regeneração nervosa periférica, aplicada em diferentes regimes após a lesão do nervo ciático em camundongos. MÉTODOS: Foram utilizados trinta camundongos machos (Swiss) divididos em: naive; sham; controle; LBI-01 (660 nm, 16,8 J de energia total emitida em 1 dia); LBI-04 (660 nm, 4,2 J por dia, 16,8 J de energia total emitida em 4 dias); LBI-28, (660 nm, 0,6 J por dia, 16,8 J de energia total emitida durante 28 dias). Os animais foram avaliados utilizando a hiperalgesia térmica, Índice Funcional do Ciático (IFC) e Índice estático do ciático (IEC). Os dados foram obtidos na linha de base e após 7, 14, 21, e 28 dias após a cirurgia. RESULTADOS: Para o IFC e IEC, todos os grupos mostraram um aumento no valor e diferenças significativas em relação ao grupo de controle, e o grupo LBI-04 apresentou os melhores resultados, alcançando valor basal no 21° dia dentre os que foram submetidos a TFBM. Na avaliação da hiperalgesia térmica, houve aumento do tempo de resposta com diferença significativa no 14° dia de avaliação no grupo LBI-04. CONCLUSÃO: A aplicação de 16,8 J foi eficaz na regeneração do nervo ciático quando distribuída ao longo dos 4 primeiros dias pós-lesão, com dose diária de 4,2 J/ponto.


Assuntos
Animais , Masculino , Camundongos , Neuropatia Ciática/radioterapia , Terapia com Luz de Baixa Intensidade , Regeneração Nervosa , Procedimentos Cirúrgicos Operatórios , Lesões por Esmagamento , Hiperalgesia , Lasers
20.
Acta Cir Bras ; 35(4): e202000405, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555937

RESUMO

PURPOSE: To investigate the effects of Chemically Extracted Acellular Nerves (CEANs) when combined with Adipose-Derived mesenchymal Stem Cell (ADSC) transplantation on the repair of sciatic nerve defects in rabbits. METHODS: A total of 71 six-month-old Japanese rabbit were used in this study. Twenty rabbits served as sciatic nerve donors, while the other 51 rabbits were randomly divided into Autologous Nerve Transplantation Group (ANT, n=17), CEAN group (n=17) and CEAN-ADSCs group (n=17). In all these groups, the rabbit's left sciatic nerves were injured before the experiment, and the uninjured sciatic nerves on their right side were used as the control (CON). Electrophysiological tests were carried out and sciatic nerves were prepared for histomorphology and stretch testing at 24 weeks post-transplant. RESULTS: There were significant differences between ANT and Con groups in amplitude (AMP): P=0.031; motor nerve conduction velocity (MNCV): P=0.029; Maximum stress: P=0.029; and Maximum strain P=0.027. There were also differences between the CEAN and CEAN+ADSCs groups in AMP: P=0.026, MNCV: P=0.024; Maximum stress: P=0.025 and Maximum strain: P=0.030. No significant differences in these parameters were observed when comparing the ANT and CEAN+SACN groups (MNCV: P=0.071) or the CEAN and ANT groups (Maximum stress: P=0.069; Maximum strain P=0.077). CONCLUSION: Addition of ADSCs has a significant impact on the recovery of nerve function, morphology, and tensile mechanical properties following sciatic nerve injury.


Assuntos
Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais , Tecido Nervoso/transplante , Neuropatia Ciática/fisiopatologia , Neuropatia Ciática/cirurgia , Animais , Fenômenos Biomecânicos , Eletromiografia , Masculino , Regeneração Nervosa/fisiologia , Tecido Nervoso/citologia , Coelhos , Valores de Referência , Reprodutibilidade dos Testes , Nervo Isquiático/fisiopatologia , Nervo Isquiático/cirurgia , Resultado do Tratamento
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