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1.
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
2.
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
3.
Muscle Nerve ; 62(2): 239-246, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32415858

RESUMO

BACKGROUND: Compound muscle action potential (CMAP) scan and MScanFit have been used to understand the consequences of denervation and reinnervation. This study aimed to monitor these parameters during Wallerian degeneration (WD) after acute nerve transections (ANT). METHODS: Beginning after urgent surgery, CMAP scans were recorded at 1-2 day intervals in 12 patients with ANT of the ulnar or median nerves, by stimulating the distal stump (DS). Stimulus intensities (SI), steps, returners, and MScanFit were calculated. Studies were grouped according to the examination time after ANT. Results were compared with those of 27 controls. RESULTS: CMAP amplitudes and MScanFit progressively declined, revealing a positive correlation with one another. SIs were higher in WD groups than controls. Steps appeared or disappeared in follow-up scans. The late WD group had higher returner% than the early WD and control groups. CONCLUSIONS: MScanFit can monitor neuromuscular dysfunction during WD. SIs revealed excitability changes in DS.


Assuntos
Potenciais de Ação/fisiologia , Nervo Mediano/fisiopatologia , Neurônios Motores/fisiologia , Condução Nervosa/fisiologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Nervo Ulnar/fisiopatologia , Degeneração Walleriana/fisiopatologia , Adolescente , Adulto , Progressão da Doença , Eletrodiagnóstico , Eletromiografia , Feminino , Humanos , Masculino , Nervo Mediano/lesões , Nervo Mediano/cirurgia , Pessoa de Meia-Idade , Traumatismos dos Nervos Periféricos/cirurgia , Nervo Ulnar/lesões , Nervo Ulnar/cirurgia , Adulto Jovem
4.
J Vasc Interv Radiol ; 31(6): 912-916.e1, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32376178

RESUMO

Eight patients who underwent percutaneous cryoablation of mixed and/or motor nerves over a period of 5 years were identified. Distances from the ablation sites to origins of distal musculature were measured, and times to initial clinical recovery were collected. Strength progression over time following muscle activation was also collected and analyzed. All patients demonstrated activation of all muscles distal to the ablation, and the calculated mean rate of nerve regeneration based on distance to the origin of the assessed musculature and time to muscle activation for the group was 1.5 mm/day ± 1.1.


Assuntos
Criocirurgia , Denervação Muscular/métodos , Força Muscular , Músculo Esquelético/inervação , Regeneração Nervosa , Dor/cirurgia , Traumatismos dos Nervos Periféricos/fisiopatologia , Nervos Periféricos/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Criocirurgia/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurônios Motores/patologia , Denervação Muscular/efeitos adversos , Dor/diagnóstico , Dor/fisiopatologia , Traumatismos dos Nervos Periféricos/diagnóstico , Traumatismos dos Nervos Periféricos/etiologia , Traumatismos dos Nervos Periféricos/patologia , Nervos Periféricos/patologia , Nervos Periféricos/fisiopatologia , Estudos Prospectivos , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
5.
J Neurosci ; 40(22): 4297-4308, 2020 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-32371602

RESUMO

Neuropathic pain is an intractable medical condition with few or no options for effective treatment. Emerging evidence shows a strong structure-function relationship between dendritic spine dysgenesis and the presence of neuropathic pain. Postmortem tissue analyses can only imply dynamic structural changes associated with injury-induced pain. Here, we profiled the in vivo dynamics of dendritic spines over time on the same superficial dorsal horn (lamina II) neurons before and after peripheral nerve injury-induced pain. We used a two-photon, whole-animal imaging paradigm that permitted repeat imaging of the same dendritic branches of these neurons in C57/Bl6 Thy1-YFP male mice. Our study demonstrates, for the first time, the ongoing, steady-state changes in dendritic spine dynamics in the dorsal horn associated with peripheral nerve injury and pain. Ultimately, the relationship between altered dendritic spine dynamics and neuropathic pain may serve as a structure-based opportunity to investigate mechanisms of pain following injury and disease.SIGNIFICANCE STATEMENT This work is important because it demonstrates for the first time: (1) the powerful utility of intravital study of dendritic spine dynamics in the superficial dorsal horn; (2) that nerve injury-induced pain triggers changes in dendritic spine steady-state behavior in the spinal cord dorsal horn; and (3) this work opens the door to further investigations in vivo of spinal cord dendritic spine dynamics in the context of injury and disease.


Assuntos
Espinhas Dendríticas/patologia , Traumatismos dos Nervos Periféricos/patologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência por Excitação Multifotônica , Traumatismos dos Nervos Periféricos/fisiopatologia , Corno Dorsal da Medula Espinal/patologia , Corno Dorsal da Medula Espinal/fisiopatologia
6.
Cell Mol Life Sci ; 77(20): 3977-3989, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32277262

RESUMO

The great plasticity of Schwann cells (SCs), the myelinating glia of the peripheral nervous system (PNS), is a critical feature in the context of peripheral nerve regeneration following traumatic injuries and peripheral neuropathies. After a nerve damage, SCs are rapidly activated by injury-induced signals and respond by entering the repair program. During the repair program, SCs undergo dynamic cell reprogramming and morphogenic changes aimed at promoting nerve regeneration and functional recovery. SCs convert into a repair phenotype, activate negative regulators of myelination and demyelinate the damaged nerve. Moreover, they express many genes typical of their immature state as well as numerous de-novo genes. These genes modulate and drive the regeneration process by promoting neuronal survival, damaged axon disintegration, myelin clearance, axonal regrowth and guidance to their former target, and by finally remyelinating the regenerated axon. Many signaling pathways, transcriptional regulators and epigenetic mechanisms regulate these events. In this review, we discuss the main steps of the repair program with a particular focus on the molecular mechanisms that regulate SC plasticity following peripheral nerve injury.


Assuntos
Plasticidade Celular/fisiologia , Regeneração Nervosa/fisiologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Células de Schwann/fisiologia , Animais , Axônios/fisiologia , Humanos , Bainha de Mielina/fisiologia , Nervo Isquiático/fisiologia , Transdução de Sinais/fisiologia
7.
J Vasc Interv Radiol ; 31(6): 903-911, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32340861

RESUMO

PURPOSE: To characterize the utility of monitoring transcranial electrical motor evoked potentials (TCeMEPs) and somatosensory evoked potentials (SSEPs) for neural thermoprotection during musculoskeletal tumor ablations. MATERIALS AND METHODS: Retrospective review of 29 patients (16 male; median age, 46 y; range, 7-77 y) who underwent musculoskeletal tumor radiofrequency ablation (n = 8) or cryoablation (n = 22) with intraprocedural TCeMEP and SSEP monitoring was performed. The most common tumor histologies were osteoid osteoma (n = 6), venous malformation (n = 5), sarcoma (n = 5), renal cell carcinoma (n = 4), and non-small-cell lung cancer (n = 3). The most common tumor sites were spine (n = 22) and lower extremities (n = 4). Abnormal TCeMEP change was defined by 100-V increase above baseline threshold activation for a given myotome; abnormal SSEP change was defined by 60% reduction in baseline amplitude and/or 10% increase in latency. RESULTS: Abnormal changes in TCeMEP (n = 9; 30%) and/or SSEP (n = 5; 17%) occurred in 12 procedures (40%) and did not recover in 5 patients. Patients with unchanged TCeMEP/SSEP activities throughout the procedure (n = 18) did not have motor or sensory symptoms after the procedure; 3 (60%) with unrecovered activity changes and 2 (29%) with transient activity changes had new motor (n = 1) or sensory (n = 4) symptoms. Relative risk for neurologic sequelae for patients with unrecovered TCeMEP/SSEP changes vs those with transient or no changes was 7.50 (95% confidence interval, 1.66-33.9; P = .009). CONCLUSIONS: Abnormal activity changes of TCeMEP or SSEP during percutaneous ablative procedures correlate with postprocedural neurologic sequelae.


Assuntos
Neoplasias Ósseas/cirurgia , Criocirurgia , Potencial Evocado Motor , Potenciais Somatossensoriais Evocados , Monitorização Neurofisiológica Intraoperatória , Neoplasias Musculares/cirurgia , Traumatismos dos Nervos Periféricos/prevenção & controle , Ablação por Radiofrequência , Adolescente , Adulto , Idoso , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Criança , Criocirurgia/efeitos adversos , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/diagnóstico por imagem , Neoplasias Musculares/patologia , Traumatismos dos Nervos Periféricos/diagnóstico , Traumatismos dos Nervos Periféricos/etiologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Valor Preditivo dos Testes , Ablação por Radiofrequência/efeitos adversos , Tempo de Reação , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Estimulação Transcraniana por Corrente Contínua , Resultado do Tratamento , Adulto Jovem
8.
Proc Natl Acad Sci U S A ; 117(10): 5463-5471, 2020 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-32079726

RESUMO

Chronic pain is a major clinical problem of which the mechanisms are incompletely understood. Here, we describe the concept that PI16, a protein of unknown function mainly produced by fibroblasts, controls neuropathic pain. The spared nerve injury (SNI) model of neuropathic pain increases PI16 protein levels in fibroblasts in dorsal root ganglia (DRG) meninges and in the epi/perineurium of the sciatic nerve. We did not detect PI16 expression in neurons or glia in spinal cord, DRG, and nerve. Mice deficient in PI16 are protected against neuropathic pain. In vitro, PI16 promotes transendothelial leukocyte migration. In vivo, Pi16 -/- mice show reduced endothelial barrier permeability, lower leukocyte infiltration and reduced activation of the endothelial barrier regulator MLCK, and reduced phosphorylation of its substrate MLC2 in response to SNI. In summary, our findings support a model in which PI16 promotes neuropathic pain by mediating a cross-talk between fibroblasts and the endothelial barrier leading to barrier opening, cellular influx, and increased pain. Its key role in neuropathic pain and its limited cellular and tissue distribution makes PI16 an attractive target for pain management.


Assuntos
Fibroblastos/enzimologia , Neuralgia/genética , Proteínas Secretadas Inibidoras de Proteinases/genética , Animais , Movimento Celular , Dor Crônica , Modelos Animais de Doenças , Células Endoteliais/fisiologia , Gânglios Espinais , Leucócitos/fisiologia , Meninges/citologia , Camundongos Knockout , Traumatismos dos Nervos Periféricos/fisiopatologia , Nervo Isquiático/enzimologia
9.
Nat Commun ; 11(1): 869, 2020 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-32054836

RESUMO

Spinal disinhibition has been hypothesized to underlie pain hypersensitivity in neuropathic pain. Apparently contradictory mechanisms have been reported, raising questions on the best target to produce analgesia. Here, we show that nerve injury is associated with a reduction in the number of inhibitory synapses in the spinal dorsal horn. Paradoxically, this is accompanied by a BDNF-TrkB-mediated upregulation of synaptic GABAARs and by an α1-to-α2GABAAR subunit switch, providing a mechanistic rationale for the analgesic action of the α2,3GABAAR benzodiazepine-site ligand L838,417 after nerve injury. Yet, we demonstrate that impaired Cl- extrusion underlies the failure of L838,417 to induce analgesia at high doses due to a resulting collapse in Cl- gradient, dramatically limiting the benzodiazepine therapeutic window. In turn, enhancing KCC2 activity not only potentiated L838,417-induced analgesia, it rescued its analgesic potential at high doses, revealing a novel strategy for analgesia in pathological pain, by combined targeting of the appropriate GABAAR-subtypes and restoring Cl- homeostasis.


Assuntos
Analgésicos/farmacologia , Cloretos/metabolismo , Neuralgia/tratamento farmacológico , Neuralgia/fisiopatologia , Receptores de GABA-A/fisiologia , Analgesia/métodos , Analgésicos/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Fluorbenzenos/metabolismo , Fluorbenzenos/farmacologia , Agonistas de Receptores de GABA-A/farmacologia , Transporte de Íons/efeitos dos fármacos , Ligantes , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Traumatismos dos Nervos Periféricos/patologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Ratos , Ratos Sprague-Dawley , Receptor trkB/metabolismo , Simportadores/metabolismo , Sinapses/efeitos dos fármacos , Sinapses/metabolismo , Triazóis/metabolismo , Triazóis/farmacologia
10.
Neurobiol Aging ; 89: 1-11, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32008855

RESUMO

Older individuals have an elevated risk for chronic pain as half of all individuals over 65 years old have at least one chronic pain condition. Unfortunately, relevant assessment tools and recommendations for chronic pain management targeting older adults are lacking. This study explores changes in response to pain between young (2-3 months old) and geriatric (20-24 months old) ages using mice. Although cutaneous thresholds to brisk stimuli (von Frey and radiant heat assays) were not affected, behavioral responses to tonic stimuli (acetone and capsaicin assays) were more pronounced in geriatric animals. After nerve injury, geriatric mice present an altered neuropathic pain profile with hypersensitivity to mechanical stimuli but not acetone and an impairment in conditioned noxious stimuli avoidance. This altered behavioral response pattern was associated with an abnormal monoaminergic signature in the medial prefrontal cortex, suggesting decreased COMT function. We conclude that young and geriatric mice exhibit different behavioral and physiological responses to the experience of pain, suggesting that knowledge and practices must be adjusted for geriatric populations.


Assuntos
Envelhecimento/fisiologia , Comportamento/fisiologia , Dor Crônica/fisiopatologia , Limiar Sensorial , Acetona , Envelhecimento/psicologia , Animais , Monoaminas Biogênicas/fisiologia , Capsaicina , Dor Crônica/etiologia , Dor Crônica/psicologia , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos C57BL , Traumatismos dos Nervos Periféricos/fisiopatologia , Estimulação Física , Córtex Pré-Frontal/fisiologia
11.
Neurourol Urodyn ; 39(3): 916-925, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32040866

RESUMO

AIMS: The urethral dysfunction produced by a rat model of peripheral neurogenic detrusor underactivity (DU) using pelvic nerve crush (PNC) injury was characterized and then tested with the administration of tadalafil, a phosphodiesterase type 5 (PDE 5) inhibitor. METHODS: Ten days after producing PNC rats, awake cystometrograms (CMGs) and isovolumetric cystometrograms with urethral perfusion pressure (IC-UPP) measurements were performed. Also, in control rats, IC-UPP was recorded before and after intravenous atropine administration to determine if the reduction of bladder contraction pressure affects urethral relaxation during voiding. Then, CMG and IC-UPP measurements in PNC rats were recorded after intravenous administration of tadalafil. Lastly, real-time polymerase chain reaction was used to measure transcript levels of neuronal nitric oxide synthases (nNOS), endothelial nitric oxide synthases, and PDE 5 in urethral specimens from PNC and control rats. RESULTS: PNC rats demonstrated the characteristics of DU in CMG. Also, PNC rats exhibited significant decreases in isovolumetric bladder contraction amplitudes and urethral relaxation. Atropine attenuated the amplitude of isovolumetric bladder contractions; however, atropine did not affect urethral relaxation in control rats. Tadalafil decreased postvoid residual and increased voiding efficiency without changing bladder contraction amplitude in PNC rats. Also, tadalafil improved the amplitude of urethral relaxation during bladder contraction in PNC rats. Urethral nNOS transcript levels were upregulated in PNC rats compared to control rats. CONCLUSIONS: PNC rats revealed both DU and impaired urethral relaxation. PDE 5 inhibition in PNC rats enhanced urethral relaxation during voiding, resulting in improved voiding efficiency. Thus, urethral dysfunction could be a potential target for the treatment of inefficient voiding associated with neurogenic DU.


Assuntos
Traumatismos dos Nervos Periféricos/fisiopatologia , Inibidores da Fosfodiesterase 5/farmacologia , Tadalafila/farmacologia , Uretra/efeitos dos fármacos , Bexiga Urinaria Neurogênica/fisiopatologia , Bexiga Inativa/fisiopatologia , Bexiga Urinária/efeitos dos fármacos , Micção/efeitos dos fármacos , Animais , Lesões por Esmagamento/fisiopatologia , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5 , Feminino , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Pelve , Ratos , Ratos Sprague-Dawley , Uretra/inervação , Uretra/metabolismo , Uretra/fisiopatologia , Bexiga Urinária/inervação , Bexiga Urinária/fisiopatologia , Micção/fisiologia
13.
J Clin Neurosci ; 72: 370-377, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31952974

RESUMO

The aim of this study was to determine the curative effects of high-dose (100 mg/kg) melatonin on peripheral nerve injury. Forty male Wistar albino rats were randomized into four groups as sham, vehicle, melatonin, and ischemia and their right sciatic nerves were exposed. The process was terminated in the sham group. In the other groups, nerve injury was induced by clip compression. The vehicle group was intraperitoneally administered ethanol 0.1 cc (melatonin solvent), while the melatonin group was intraperitoneally administered a single dose of melatonin (100 mg/kg). Following the surgery, sciatic nerve functional index (SFI) was measured using walking track analysis on days 7, 14, and 21, and latency, amplitude, and muscle action potentials (MAP) field values were measured using electroneuromyography (ENMG) on day 21. Histopathologically, edema, axonal degeneration, myelin damage, and inflammatory response were evaluated in all groups. SFI values were noted to be statistically significantly different among the vehicle, melatonin, and ischemia groups, and the melatonin group showed a faster recovery. In the ENMG evaluations, higher amplitude and field values in the melatonin group indicated that melatonin accelerated peripheral nerve recovery. Histopathologically, although fibers with loss of myelin were identified in the melatonin group, the myelin sheath was preserved in general and the axonal structure was noted to be normal. A single injection of high-dose melatonin was found to preserve myelin sheath, prevent axonal loss, and accelerate functional recovery during the nerve regeneration in peripheral nerve injury.


Assuntos
Melatonina/uso terapêutico , Regeneração Nervosa/efeitos dos fármacos , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Nervo Isquiático/lesões , Nervo Isquiático/fisiopatologia , Animais , Axônios/patologia , Masculino , Bainha de Mielina/patologia , Traumatismos dos Nervos Periféricos/patologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Ratos , Ratos Wistar , Recuperação de Função Fisiológica/fisiologia , Nervo Isquiático/patologia
14.
Exp Neurol ; 327: 113215, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31991126

RESUMO

Neurogenic differentiation 1 (NeuroD1) is mainlyexpressed in developing neurons where it plays critical roles in neuronal maturation and neurite elongation. The potential role and mechanism of NeuroD1 in adult axonal regeneration is not clear. The present study used synapsin (SYN) Cre and AAV9-Flex vectors to conditionally overexpress NeuroD1 in adult spinal neurons and found that NeuroD1 overexpression significantly accelerated axonal regeneration and functional recovery after sciatic nerve injury. Further in vitro and in vivo experiments suggested that the mechanism of NeuroD1 promotion on axonal regeneration was related to its regulation of the expression of neurotrophin BDNF and its receptor TrkB as well as a microtubule severing protein spastin.


Assuntos
Axônios/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Regeneração Nervosa/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Traumatismos dos Nervos Periféricos/metabolismo , Nervo Isquiático/lesões , Nervos Espinhais/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Feminino , Camundongos , Atividade Motora/fisiologia , Proteínas do Tecido Nervoso/genética , Traumatismos dos Nervos Periféricos/fisiopatologia , Receptor trkB/metabolismo , Recuperação de Função Fisiológica/fisiologia
15.
Int J Biol Sci ; 16(1): 116-134, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31892850

RESUMO

Peripheral nerve injury is a complex condition with a variety of signs and symptoms such as numbness, tingling, jabbing, throbbing, burning or sharp pain. Peripheral nerves are fragile in nature and can easily get damaged due to acute compression or trauma which may lead to the sensory and motor functions deficits and even lifelong disability. After lesion, the neuronal cell body becomes disconnected from the axon's distal portion to the injury site leading to the axonal degeneration and dismantlement of neuromuscular junctions of targeted muscles. In spite of extensive research on this aspect, complete functional recovery still remains a challenge to be resolved. This review highlights detailed pathophysiological events after an injury to a peripheral nerve and the associated factors that can either hinder or promote the regenerative machinery. In addition, it throws light on the available therapeutic strategies including supporting therapies, surgical and non-surgical interventions to ameliorate the axonal regeneration, neuronal survival, and reinnervation of peripheral targets. Despite the availability of various treatment options, we are still lacking the optimal treatments for a perfect and complete functional regain. The need for the present age is to discover or design such potent compounds that would be able to execute the complete functional retrieval. In this regard, plant-derived compounds are getting more attention and several recent reports validate their remedial effects. A plethora of plants and plant-derived phytochemicals have been suggested with curative effects against a number of diseases in general and neuronal injury in particular. They can be a ray of hope for the suffering individuals.


Assuntos
Traumatismos dos Nervos Periféricos/metabolismo , Traumatismos dos Nervos Periféricos/fisiopatologia , Nervos Periféricos/metabolismo , Nervos Periféricos/fisiopatologia , Animais , Humanos , Regeneração Nervosa/fisiologia , Plasticidade Neuronal/genética , Plasticidade Neuronal/fisiologia , Recuperação de Função Fisiológica/genética , Recuperação de Função Fisiológica/fisiologia
16.
Ann Vasc Surg ; 62: 70-75, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31207398

RESUMO

BACKGROUND: The objective of this study was to characterize phrenic nerve and brachial plexus variation encountered during supraclavicular decompression for neurogenic thoracic outlet syndrome and to identify associated postoperative neurologic complications. METHODS: A multicenter retrospective review was performed to evaluate anatomic variation of the phrenic nerve and brachial plexus from November 2010 to July 2018. After initial characterization, the following two groups were identified: variant anatomy (VA) group and standard anatomy (SA) group. Complications were analyzed and compared between the two groups. RESULTS: In total, 105 patients were identified, and 100 patients met inclusion criteria. Any anatomic variation of the standard course or configuration of the phrenic nerve and/or brachial plexus was encountered in 47 (47%) patients. Phrenic nerve anatomic variations were identified in 28 (28%) patients. These included 9 duplicated nerves, 6 lateral accessory nerves, 8 medial displacement, and 5 lateral displacement. Brachial plexus anatomic variation was found in 34 (34%) patients. The most common variant configuration of a fused middle and inferior trunk was identified in 25 (25%) patients. Combined phrenic nerve and brachial plexus anatomic variation was demonstrated in 15 (15%) patients. The VA and SA groups consisted of 47 and 53 patients, respectively. Transient phrenic nerve injury with postoperative elevation of the ipsilateral hemidiaphragm was documented in 3 (6.4%) patients in the VA group and 6 (11.3%) patients in the SA group (P = 0.49). Permanent phrenic nerve injury was identified in 1 (2.1%) patient in the VA group (P = 0.47) and none in the SA group. Transient brachial plexopathy was encountered in 1 (1.9%) patient in the SA group (P = 1.0) with full recovery to normal function. CONCLUSIONS: Anatomic variability of the phrenic nerve and brachial plexus are encountered more frequently than previously reported. While the incidence of nerve injury is low, surgeons operating within the thoracic aperture should be familiar with variant anatomy to reduce postoperative complications.


Assuntos
Neuropatias do Plexo Braquial/etiologia , Plexo Braquial/anormalidades , Descompressão Cirúrgica/efeitos adversos , Traumatismos dos Nervos Periféricos/etiologia , Nervo Frênico/anormalidades , Síndrome do Desfiladeiro Torácico/cirurgia , Adulto , Plexo Braquial/lesões , Plexo Braquial/fisiopatologia , Neuropatias do Plexo Braquial/fisiopatologia , Feminino , Humanos , Masculino , Maryland , Traumatismos dos Nervos Periféricos/fisiopatologia , Philadelphia , Nervo Frênico/lesões , Nervo Frênico/fisiopatologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Síndrome do Desfiladeiro Torácico/diagnóstico por imagem , Síndrome do Desfiladeiro Torácico/fisiopatologia , Resultado do Tratamento
17.
Muscle Nerve ; 61(6): 726-739, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31883129

RESUMO

Despite advances in surgery, the reconstruction of segmental nerve injuries continues to pose challenges. In this review, current neurobiology regarding regeneration across a nerve defect is discussed in detail. Recent findings include the complex roles of nonneuronal cells in nerve defect regeneration, such as the role of the innate immune system in angiogenesis and how Schwann cells migrate within the defect. Clinically, the repair of nerve defects is still best served by using nerve autografts with the exception of small, noncritical sensory nerve defects, which can be repaired using autograft alternatives, such as processed or acellular nerve allografts. Given current clinical limits for when alternatives can be used, advanced solutions to repair nerve defects demonstrated in animals are highlighted. These highlights include alternatives designed with novel topology and materials, delivery of drugs specifically known to accelerate axon growth, and greater attention to the role of the immune system.


Assuntos
Regeneração Nervosa/fisiologia , Traumatismos dos Nervos Periféricos/cirurgia , Procedimentos Cirúrgicos Reconstrutivos/tendências , Tecidos Suporte/tendências , Transplantes/transplante , Animais , Humanos , Traumatismos dos Nervos Periféricos/fisiopatologia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Transplante Autólogo/métodos , Transplante Autólogo/tendências
19.
Neurol India ; 67(6): 1419-1422, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31857526

RESUMO

Peripheral nerve injuries are a heterogeneous and distinct group of disorders that are secondary to various causes commonly including motor vehicle accidents, falls, industrial accidents, household accidents, and penetrating trauma. The earliest classification of nerve injuries was given by Seddon and Sunderland, which holds true till date and is commonly used. Neuropraxia, axonotmesis, and neurotmesis are the three main types of nerve injuries. The electrophysiological studies including nerve conduction studies (NCS) and electromyography (EMG) play a key role and are now considered an extension of the clinical examination in patients with peripheral nerve injuries. The electrophysiological results should be interpreted in the light of clinical examination. These studies help in localizing the site of lesion, determine the type and severity of lesion, and help in prognosticating. In neuropraxia, the compound muscle action potential (CMAP) and sensory nerve action potential (SNAP) are elicitable on stimulating the nerve distal to the site of the lesion but demonstrate conduction block on proximal stimulation. The electrodiagnostic findings in axonotmesis and neurotmesis are similar. After few days of injury, Wallerian degeneration sets in with failure to record CMAP and SNAP. Intraoperative technique involves recording from the peripheral nerves during the intraoperative period and has proved useful in the surgical management of nerve injuries and helps in identifying the injured nerve, to determine whether the nerve is in continuity and in localizing the site of lesion. Intraoperative monitoring also helps in identifying the nerve close to an ongoing surgery so that surgical damage to the nerve can be prevented.


Assuntos
Condução Nervosa/fisiologia , Traumatismos dos Nervos Periféricos/diagnóstico , Nervos Periféricos/fisiopatologia , Potenciais de Ação/fisiologia , Eletrodiagnóstico , Eletromiografia , Humanos , Monitorização Neurofisiológica Intraoperatória , Procedimentos Neurocirúrgicos , Traumatismos dos Nervos Periféricos/fisiopatologia , Traumatismos dos Nervos Periféricos/cirurgia , Nervos Periféricos/cirurgia , Prognóstico
20.
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
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