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1.
J Comput Assist Tomogr ; 43(6): 976-980, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31688247

RESUMO

Endometriosis (EN) is a common gynecological condition characterized by the presence of functional endometrium located outside the uterine cavity. Sciatic nerve (SN) is rarely affected by EN. Magnetic resonance imaging allows a direct visualization of the spinal and SN, and it is the modality of choice for the study of SN involvement in extrapelvic EN. We report a case of an endometrioma located in the right SN with a systematic review of the literature.


Assuntos
Endometriose/diagnóstico por imagem , Nervo Isquiático/patologia , Ciática/diagnóstico por imagem , Adulto , Endometriose/complicações , Endometriose/cirurgia , Feminino , Humanos , Laparoscopia , Imagem por Ressonância Magnética/métodos , Nervo Isquiático/diagnóstico por imagem , Nervo Isquiático/cirurgia , Ciática/etiologia , Ciática/cirurgia , Resultado do Tratamento
2.
Pan Afr Med J ; 33: 242, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31692794

RESUMO

The sciatic nerve is the terminal branch of the sacral plexus. Sciatalgia is a nerve root pain. In most cases, sciatica originates from degenerative disc disease. Tumor involving the sciatic nerve is extremely rare. We here report the case of a 33-year old patient with nerve tumor detected on MRI performed for drug-resistant sciatica. Tumor involving the sciatic nerve is rare and diagnosis is difficult. MRI data are crucial for establishing an effective surgical approach.


Assuntos
Imagem por Ressonância Magnética/métodos , Neurilemoma/diagnóstico por imagem , Neurofibroma/diagnóstico por imagem , Nervo Isquiático/diagnóstico por imagem , Adulto , Diagnóstico Diferencial , Humanos , Masculino , Nervo Isquiático/patologia , Ciática/diagnóstico
3.
J Comput Assist Tomogr ; 43(6): 953-957, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31738201

RESUMO

PURPOSE: Compression of the sciatic nerve in its path along the piriformis muscle can produce sciatica-like symptoms. There are 6 predominant types of sciatic nerve variations with type 1 being the most common (84.2%), followed by type 2 (13.9%). However, there is scarce literature on the prevalence of sciatic nerve variation in those diagnosed with sciatica. MATERIALS AND METHODS: The charts of 95 patients clinically diagnosed with sciatica who had a magnetic resonance imaging of the pelvis/hip were retrospectively studied. All patients had T1-weighted axial, coronal, and sagittal images. Magnetic resonance imagings were interpreted separately by 2 board-certified fellowship-trained musculoskeletal radiologists to identify the sciatic nerve variant. RESULTS: Seven cases were excluded because of inadequate imaging. Of the remaining 88 patients, 5 had bilateral sciatica resulting in a sample size of 93 limbs. Fifty-two (55.9%) had type 1 sciatic nerve anatomy, 39 (41.9%) had type 2, and 2 (2.2%) had type 3. The proportions of type 1 and 2 variations were significantly different from the normal distribution (P < 0.001), whereas type 3, 4, 5, and 6 variants were not (P = 1.00). CONCLUSIONS: There is strong statistical significance regarding the relationship between sciatic nerve variation and the clinical diagnosis of sciatica. Preoperative magnetic resonance imaging can be considered in sciatica patients to prevent iatrogenic injury in pelvic surgery.


Assuntos
Síndrome do Músculo Piriforme/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Nervo Isquiático/diagnóstico por imagem , Ciática/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Estudos Retrospectivos , Nervo Isquiático/patologia , Tíbia/diagnóstico por imagem , Tíbia/inervação
4.
Eur Cytokine Netw ; 30(2): 59-66, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31486397

RESUMO

Recent studies have demonstrated that nicotine exhibited anti-inflammatory and neuroprotective properties by interacting with the alpha 7 nicotinic acetylcholine receptor (α7nAChR). However, the role of nicotine in regeneration during peripheral nerve injury has not been elucidated. The aim of this study was to investigate whether nicotine down-regulated production of proinflammatory cytokines and promoted peripheral nerve regeneration in rats. Rats challenged with sciatic nerve crush injury were treated with nicotine (1.5 mg/kg), three times per day. The expression of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin (IL-1ß), pinch test results, growth-associated protein 43 (GAP-43) expression, morphometric analyses, and the sciatic functional indexes were determined in sciatic nerves. Treatment with nicotine decreased local levels of TNF-α and IL-1ß, and increased the expression of GAP-43. Nicotine also improved nerve regeneration and functional recovery. The overall protective effects of nicotine were reversed by concomitant treatment with α7nACHR antagonist methyllycaconitine, indicating that nicotine exerted its specific anti-inflammatory and neuroprotective effects through the α7nAChR. These findings show that nicotine administration can provide a potential therapeutic pathway for the treatment of peripheral nerve injury, by a direct protective effect through the α7nAChR-mediated cholinergic anti-inflammatory pathway.


Assuntos
Lesões por Esmagamento/metabolismo , Lesões por Esmagamento/patologia , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Fármacos Neuroprotetores/farmacologia , Nicotina/farmacologia , Nervo Isquiático/metabolismo , Nervo Isquiático/patologia , Animais , Modelos Animais de Doenças , Proteína GAP-43/metabolismo , Interleucina-1beta/metabolismo , Masculino , Atividade Motora/efeitos dos fármacos , Regeneração Nervosa/efeitos dos fármacos , Ratos Wistar , Nervo Isquiático/efeitos dos fármacos , Células Receptoras Sensoriais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
5.
Muscle Nerve ; 60(5): 613-620, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31397908

RESUMO

INTRODUCTION: The objective of this study is to assess the efficacy of local tacrolimus (FK506) delivery to improve outcomes in the setting of nerve transection injury. METHODS: FK506 embedded poly(lactide-co-caprolactone) films capable of extended, localized release of FK506 were developed. FK506 rate of release testing and bioactivity assay was performed. Mouse sciatic nerve transection and direct repair model was used to evaluate the effect extended, local delivery of FK506 had on nerve regeneration outcomes. RESULTS: Linear release of FK506 was observed for 30 days and released FK506 matched control levels of neurite extension in the dorsal root ganglion assay. Groups treated with local FK506 had greater gastrocnemius muscle weight, foot electromyogram, and number of axons distal of the repair site than non-FK506 groups. DISCUSSION: Results of this study indicate that extended, localized delivery of FK506 to nerve injuries can improve nerve regeneration outcomes in a mouse sciatic nerve transection and repair.


Assuntos
Imunossupressores/farmacologia , Denervação Muscular , Músculo Esquelético/efeitos dos fármacos , Regeneração Nervosa/efeitos dos fármacos , Nervo Isquiático/lesões , Tacrolimo/farmacologia , Animais , Axônios/efeitos dos fármacos , Axônios/patologia , Preparações de Ação Retardada , Eletromiografia , Gânglios Espinais/efeitos dos fármacos , Imunossupressores/administração & dosagem , Camundongos , Músculo Esquelético/patologia , Neuritos/efeitos dos fármacos , Neuritos/patologia , Procedimentos Neurocirúrgicos , Tamanho do Órgão , Traumatismos dos Nervos Periféricos , Poliésteres , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/patologia , Nervo Isquiático/cirurgia , Tacrolimo/administração & dosagem
6.
Neurochem Res ; 44(9): 2123-2138, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31376053

RESUMO

Number of ligations made in the chronic constriction injury (CCI) neuropathic pain model has raised serious concerns. We compared behavioural responses, nerve morphology and expression of pain marker, c-fos among CCI models developed with one, two, three and four ligations. The numbers of ligation(s) on sciatic nerve shows no significant difference in displaying mechanical and cold allodynia, and mechanical and thermal hyperalgesia throughout 84 days. All groups underwent similar levels of nerve degeneration post-surgery. Similar c-fos level in brain cingulate cortex, parafascicular nuclei and amygdala were observed in all CCI models compared to sham-operated group. Therefore, number of ligations does not impact intensity of pain symptoms, pathogenesis and neuronal activation. A single ligation is sufficient to develop neuropathic pain, in contrast to the established model of four ligations. This study dissects and characterises the CCI model, ascertaining a more uniform animal model to surrogate actual neuropathic pain condition.


Assuntos
Modelos Animais de Doenças , Camundongos Endogâmicos ICR , Neuralgia , Tonsila do Cerebelo/metabolismo , Tonsila do Cerebelo/patologia , Tonsila do Cerebelo/fisiopatologia , Animais , Constrição Patológica/complicações , Giro do Cíngulo/metabolismo , Giro do Cíngulo/patologia , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatologia , Núcleos Intralaminares do Tálamo/metabolismo , Núcleos Intralaminares do Tálamo/patologia , Ligadura , Masculino , Neuralgia/etiologia , Neuralgia/metabolismo , Neuralgia/patologia , Neuralgia/fisiopatologia , Medição da Dor , Proteínas Proto-Oncogênicas c-fos/metabolismo , Nervo Isquiático/lesões , Nervo Isquiático/patologia , Neuropatia Ciática/etiologia , Neuropatia Ciática/metabolismo , Neuropatia Ciática/patologia , Neuropatia Ciática/fisiopatologia
7.
Neurochem Res ; 44(9): 2092-2102, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31377996

RESUMO

The aim of this study was to evaluate the diagnostic efficacy of 18F-FDG PET/MRI in two different peripheral neuropathic pain models using the injured rat sciatic nerves. Twelve rats, with operation on left sciatic nerves, were evenly divided into three groups: sham surgery (control group), crushing injury and chronic constriction injury (CCI) (experimental groups). The nerve damage was assessed at 3 weeks postoperatively using following methods: paw withdrawal threshold values (RevWT), maximum standardized uptake values on PET/MRI images (SUVR), and counting the number of myelinated axons in proximal and distal sites of nerve injury (MAxR). The results were quantified and statistically analyzed. Compared to the control group, the crushing injury demonstrated significant differences in RevWT (p < 0.0001) and SUVR (p = 0.027) and the CCI group demonstrated significant differences in RevWT (p < 0.0001), SUVR (p = 0.001) and MAxR (p = 0.048). There were no significant differences between the two experimental groups for all assessments. Correlation analysis demonstrated that RevWT and SUVR assessments were highly correlated (r = -- 0.710, p = 0.010), and SUVR and MAxR were highly correlated (r = 0.611, p = 0.035). However, there was no significant correlation between RevWT and MAxR. The PET scan may be a valuable imaging modality to enable noninvasive, objective diagnosis of neuropathic pain caused by peripheral nerve injury. Also, MRI fused with PET may help clarify the anatomic location of soft tissue structures, including the peripheral nerves.


Assuntos
Fluordesoxiglucose F18/química , Neuralgia/diagnóstico por imagem , Traumatismos dos Nervos Periféricos/diagnóstico por imagem , Compostos Radiofarmacêuticos/química , Neuropatia Ciática/diagnóstico por imagem , Animais , Radioisótopos de Flúor/química , Imagem por Ressonância Magnética , Masculino , Traumatismos dos Nervos Periféricos/patologia , Tomografia por Emissão de Pósitrons , Ratos Sprague-Dawley , Nervo Isquiático/lesões , Nervo Isquiático/patologia , Neuropatia Ciática/patologia
8.
Pathologica ; 111(2): 67-69, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31388198

RESUMO

Peripheral nerve mucoid degeneration (PNMD) is a rare non-neoplastic degenerative condition characterized by endoneural deposit of mucoid matrix. Herein, we report a case of PNMD involving the sciatic nerve with preoperative features, surgical treatment and pathological findings.


Assuntos
Degeneração Neural/diagnóstico por imagem , Degeneração Neural/cirurgia , Doenças do Sistema Nervoso Periférico/diagnóstico por imagem , Doenças do Sistema Nervoso Periférico/cirurgia , Nervo Isquiático/diagnóstico por imagem , Nervo Isquiático/cirurgia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Nervo Isquiático/patologia
9.
BMC Womens Health ; 19(1): 95, 2019 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-31299947

RESUMO

BACKGROUND: The combination of intrapelvic and extrapelvic endometriosis is a very rare condition in gynecology. Patients with endometriosis involving the sciatic nerve are easily misdiagnosed because they usually present with atypical symptoms of endometriosis. Here, we present a rare case of an endometrioma passing through the left greater sciatic foramen. Removal of the endometriotic lesion was performed with a concomitant laparoscopic and transgluteal approach through the cooperation of gynecologists and orthopedic (neuro)surgeons. CASE PRESENTATION: A 20-year-old woman presented with complaints of severe dysmenorrhea lasting for more than 6 years and dysfunction of her left lower limb lasting for approximately 4 months. Both CT and MRI demonstrated a suspected intrapelvic and extrapelvic endometriotic cyst (7.3 cm × 8.1 cm × 6.5 cm) passing through the left greater sciatic foramen. Laparoscopic exploration showed a cyst full of dark fluid occupying the left obturator fossa and extending outside the pelvis. A novel combination of transgluteal laparoscopy was performed for complete resection of the cyst and decompression of the sciatic nerve. Postoperative pathology confirmed the diagnosis of endometriosis. Long-term follow-up observation showed persistent pain relief and lower limb function recovery in the patient. DISCUSSION AND CONCLUSIONS: When a woman complains of unexplained unilateral sciatica, especially a woman suffering from dysmenorrhea, endometriosis of the sciatica nerve should be considered as a potential etiology. Complete excision of the endometriotic lesion and adequate neurolysis (or decompression) of the sciatic nerve through the multidisciplinary cooperation of experienced gynecologists with proper training in laparoscopic pelvic (neuro)surgery and orthopedic (neuro)surgeons is effective.


Assuntos
Dismenorreia/cirurgia , Endometriose/cirurgia , Laparoscopia/métodos , Ciática/cirurgia , Dismenorreia/etiologia , Dismenorreia/patologia , Endometriose/complicações , Endometriose/patologia , Feminino , Humanos , Extremidade Inferior/patologia , Extremidade Inferior/cirurgia , Pelve/patologia , Pelve/cirurgia , Nervo Isquiático/patologia , Nervo Isquiático/cirurgia , Ciática/etiologia , Ciática/patologia , Adulto Jovem
10.
Appl Biochem Biotechnol ; 189(4): 1167-1182, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31209719

RESUMO

Moxibustion is the main alternative medicine treatment that has been beneficial to diabetic peripheral neuropathy (DPN), a common complication secondary to diabetic microvascular injury. However, the underlying protective mechanism of moxibustion against neuroinflammation remains unclear. We hypothesized that moxibustion treats DPN by regulating the balance of nuclear factor-2 erythroid-related factor-2 (Nrf2)-nuclear factor-kappa light chain enhancer of B cells (NF-кB). In vivo, diabetes was induced in rats by injecting streptozotocin (STZ; 60 mg/kg; i.p.). Moxibustion was then applied to "Zusanli" (ST 36), "Guanyuan" (BL 26), and "Yishu" (EX-B 3) acupuncture points. Nerve conduction was detected. Serum interleukin (IL)-1ß, IL-6, and IL-8 levels were determined through enzyme-linked immunosorbent assay. NF-κB and Nrf2 proteins were examined through immunoblot analysis. The mRNA of NF-κB and Nrf2 was evaluated through RT-PCR. We found that the conduction velocity and amplitude of the action potentials of sciatic nerve conduction were reduced in the DPN model group but were rescued by moxibustion treatment. Moxibustion also improved the effect of DPN on other parameters, including ultrastructural changes, NF-κB and Nrf2 expression in the sciatic nerve, and serum IL-1ß, IL-6, and IL-8 levels. Our data suggested that moxibustion may alleviate neuroinflammation by inhibiting NF-κB and by activating Nrf2. Moxibustion may also provide therapeutic effects for patients with DPN by simultaneously targeting Nrf2 and NF-κB.


Assuntos
Diabetes Mellitus Experimental , Neuropatias Diabéticas , Moxibustão , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Doenças do Sistema Nervoso Periférico , Nervo Isquiático , Animais , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/terapia , Neuropatias Diabéticas/metabolismo , Neuropatias Diabéticas/patologia , Neuropatias Diabéticas/terapia , Masculino , Doenças do Sistema Nervoso Periférico/metabolismo , Doenças do Sistema Nervoso Periférico/patologia , Doenças do Sistema Nervoso Periférico/terapia , Ratos , Ratos Wistar , Nervo Isquiático/metabolismo , Nervo Isquiático/patologia
11.
Neurochem Res ; 44(8): 1964-1976, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31218567

RESUMO

Schwann cells are essential glial cells in the peripheral nervous system (PNS), and dysfunction of Schwann cells can induce various peripheral neurodegenerative diseases. Oxidative stress has been implicated as a causative factor in degenerative nerve diseases; however, there no effective molecules are available to inhibit nerve degeneration in peripheral neurodegenerative diseases. Ethyl pyruvate (EP) is a candidate regulator of oxidative stress, targeting Schwann cells during peripheral nerve degeneration. Here, we investigated the effects of EP on axonal degradation, demyelination, transcriptional regulation, and macrophage recruitment during Wallerian degeneration of the sciatic nerve, ex vivo and in vivo. EP prevented the expression of neuronal nitric oxide synthase (NOS1), but not that of inducible nitric oxide synthase (NOS2), during Wallerian degeneration. These results suggest that effect of EP on Schwann cells may protect against peripheral nerve degeneration through its NOS1-specific regulation.


Assuntos
Inibidores Enzimáticos/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Óxido Nítrico Sintase Tipo I/antagonistas & inibidores , Piruvatos/uso terapêutico , Células de Schwann/efeitos dos fármacos , Degeneração Walleriana/prevenção & controle , Animais , Axônios/efeitos dos fármacos , Doenças Desmielinizantes/patologia , Doenças Desmielinizantes/prevenção & controle , Macrófagos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Bainha de Mielina/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-jun/metabolismo , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/patologia , Degeneração Walleriana/patologia
12.
Muscle Nerve ; 60(2): 192-201, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31093982

RESUMO

INTRODUCTION: We recently demonstrated the beneficial effects of 4-aminopyridine (4-AP), a potassium channel blocker, in enhancing remyelination and recovery of nerve conduction velocity and motor function after sciatic nerve crush injury in mice. Although muscle atrophy occurs very rapidly after nerve injury, the effect of 4-AP on muscle atrophy and intrinsic muscle contractile function is largely unknown. METHODS: Mice were assigned to sciatic nerve crush injury and no-injury groups and were followed for 3, 7, and 14 days with/without 4-AP or saline treatment. Morphological, functional, and transcriptional properties of skeletal muscle were assessed. RESULTS: In addition to improving in vivo function, 4-AP significantly reduced muscle atrophy with increased muscle fiber diameter and contractile force. Reduced muscle atrophy was associated with attenuated expression of atrophy-related genes and increased expression of proliferating stem cells. DISCUSSION: These findings provide new insights into the potential therapeutic benefits of 4-AP against nerve injury-induced muscle atrophy and dysfunction. Muscle Nerve 60: 192-201, 2019.


Assuntos
4-Aminopiridina/farmacologia , Lesões por Esmagamento/fisiopatologia , Músculo Esquelético/efeitos dos fármacos , Atrofia Muscular/patologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Bloqueadores dos Canais de Potássio/farmacologia , Remielinização/efeitos dos fármacos , Nervo Isquiático/efeitos dos fármacos , Animais , Lesões por Esmagamento/metabolismo , Lesões por Esmagamento/patologia , Proteína Forkhead Box O1/efeitos dos fármacos , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O3/efeitos dos fármacos , Proteína Forkhead Box O3/genética , Camundongos , Proteínas Musculares/efeitos dos fármacos , Proteínas Musculares/genética , Músculo Esquelético/inervação , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Atrofia Muscular/genética , Traumatismos dos Nervos Periféricos/genética , Traumatismos dos Nervos Periféricos/patologia , Regeneração/efeitos dos fármacos , Nervo Isquiático/lesões , Nervo Isquiático/patologia , Nervo Isquiático/fisiopatologia , Proteínas com Motivo Tripartido/efeitos dos fármacos , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/efeitos dos fármacos , Ubiquitina-Proteína Ligases/genética
13.
Int J Exp Pathol ; 100(2): 83-93, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31090128

RESUMO

Schwann cells (SCs) critically maintain the plasticity of the peripheral nervous system. Peripheral nerve injuries and infections stimulate SCs in order to retrieve homeostasis in neural tissues. Previous studies indicate that Mycobacterium leprae (ML) regulates the expression of key factors related to SC identity, suggesting that alterations in cell phenotype may be involved in the pathogenesis of neural damage in leprosy. To better understand whether ML restricts the plasticity of peripheral nerves, the present study sought to determine the expression of Krox-20, Sox-10, c-Jun and p75NTR in SC culture and mice sciatic nerves, both infected by ML Thai-53 strain. Primary SC cultures were stimulated with two different multiplicities of infection (MOI 100:1; MOI 50:1) and assessed after 7 and 14 days. Sciatic nerves of nude mice (NU-Foxn1nu ) infected with ML were evaluated after 6 and 9 months. In vitro results demonstrate downregulation of Krox-20 and Sox-10 along with the increase in p75NTR-immunolabelled cells. Concurrently, sciatic nerves of infected mice showed a significant decrease in Krox-20 and increase in p75NTR. Our results corroborate previous findings on the interference of ML in the expression of factors involved in cell maturation, favouring the maintenance of a non-myelinating phenotype in SCs, with possible implications for the repair of adult peripheral nerves.


Assuntos
Regulação para Baixo , Proteína 2 de Resposta de Crescimento Precoce/biossíntese , Hanseníase/metabolismo , Células de Schwann/metabolismo , Nervo Isquiático/metabolismo , Animais , Diferenciação Celular/fisiologia , Células Cultivadas , Modelos Animais de Doenças , Hanseníase/microbiologia , Hanseníase/patologia , Camundongos Nus , Mycobacterium leprae/isolamento & purificação , Plasticidade Neuronal/fisiologia , Receptores de Fator de Crescimento Neural/metabolismo , Células de Schwann/microbiologia , Células de Schwann/patologia , Nervo Isquiático/microbiologia , Nervo Isquiático/patologia , Técnicas de Cultura de Tecidos
14.
Nat Commun ; 10(1): 2361, 2019 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-31142747

RESUMO

Schwann cells ensure efficient nerve impulse conduction in the peripheral nervous system. Their development is accompanied by defined chromatin changes, including variant histone deposition and redistribution. To study the importance of variant histones for Schwann cell development, we altered their genomic distribution by conditionally deleting Ep400, the central subunit of the Tip60/Ep400 complex. Ep400 absence causes peripheral neuropathy in mice, characterized by terminal differentiation defects in myelinating and non-myelinating Schwann cells and immune cell activation. Variant histone H2A.Z is differently distributed throughout the genome and remains at promoters of Tfap2a, Pax3 and other transcriptional regulator genes with transient function at earlier developmental stages. Tfap2a deletion in Ep400-deficient Schwann cells causes a partial rescue arguing that continued expression of early regulators mediates the phenotypic defects. Our results show that proper genomic distribution of variant histones is essential for Schwann cell differentiation, and assign importance to Ep400-containing chromatin remodelers in the process.


Assuntos
Histonas/metabolismo , Doenças do Sistema Nervoso Periférico/genética , Células de Schwann/metabolismo , Nervo Isquiático/metabolismo , Fatores de Transcrição/genética , Animais , Montagem e Desmontagem da Cromatina , Regulação da Expressão Gênica no Desenvolvimento , Camundongos , Camundongos Transgênicos , Fator de Transcrição PAX3/genética , Fator de Transcrição PAX3/metabolismo , Doenças do Sistema Nervoso Periférico/metabolismo , Doenças do Sistema Nervoso Periférico/patologia , Regiões Promotoras Genéticas , Nervo Isquiático/patologia , Fator de Transcrição AP-2/genética , Fator de Transcrição AP-2/metabolismo
15.
Cell Mol Neurobiol ; 39(6): 799-808, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31011938

RESUMO

Vincristine is a toxic chemotherapeutic agent which often triggers neuropathic pain through inflammation. Morin isolated from figs (Ficus carica) exerts anti-inflammatory and neuroprotective activities. We investigated whether morin ameliorates vincristine-induced neuropathic pain and the underlying mechanism. Vincristine was injected i.p. for 10 days (day 1-5 and day 8-12). Morin was orally administered every other day from day 1 to 21. The pain behaviors were determined by measuring paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). The axons of sciatic nerves were stained with toluidine blue to study the histological abnormality. Function deficit of sciatic nerves was evaluated by sciatic functional index and the sciatic nerve conduction velocity. Neuronal excitability was assessed electrophysiologically and inflammatory mediators were detected using western blotting in dorsal root ganglia. The vincristine-induced reduction in PWT, PWL, and body weight gain was attenuated by morin. Morin restored the sciatic nerve deficits both histologically and functionally in vincristine-injected rats. The vincristine-induced neuronal hyperexcitability and increase in the expression of IL-6, NF-κB, and pNF-κB were abolished after morin administration. This study suggests that morin treatment suppressed vincristine-induced neuropathic pain by protecting the sciatic nerve and inhibiting inflammation through NF-κB pathway.


Assuntos
Flavonoides/uso terapêutico , NF-kappa B/metabolismo , Neuralgia/induzido quimicamente , Neuralgia/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Nervo Isquiático/patologia , Transdução de Sinais , Vincristina/efeitos adversos , Animais , Flavonoides/farmacologia , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/patologia , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Masculino , Fármacos Neuroprotetores/farmacologia , Ratos Sprague-Dawley , Nervo Isquiático/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
16.
Toxicol Pathol ; 47(4): 542-552, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30987532

RESUMO

Experimental autoimmune neuritis (EAN) is an animal model for Guillain-Barré syndrome (GBS), which results in neurological symptoms and histopathological changes in peripheral nerves. In this model, the correlation between the progression of the disease and the histopathological changes is not clear. To further examine histopathological changes in peripheral nerves in EAN rats, sciatic nerves were sampled at onset (day 10), peak (day 16), and recovery (days 22 and 25) of neurological symptoms in P2(57-81)-peptide-administered rats. Axon and myelin degeneration was observed by light microscopy at onset, degeneration became severe at peak, and persisted at recovery. Densities of myelinated nerve fibers and myelin areas decreased from day 10 to a minimum on day 22. Slight axon and myelin degeneration, such as accumulation of vesicles in axons and focal myelin splitting and folding, was observed by transmission electron microscopy at onset; severe degeneration, such as axonal loss, myelin ovoid, and demyelination, increased at peak; and regenerative changes, such as remyelination and enlargement of Schwann cell cytoplasm, occurred at recovery. These results suggest that EAN rats have histopathological similarities to some types of GBS patients and that EAN rats are a useful model to understand the pathogenesis of GBS.


Assuntos
Axônios/ultraestrutura , Síndrome de Guillain-Barré/patologia , Bainha de Mielina/ultraestrutura , Neurite Autoimune Experimental/patologia , Nervo Isquiático/patologia , Animais , Síndrome de Guillain-Barré/imunologia , Masculino , Microscopia Eletrônica de Transmissão , Proteína P2 de Mielina/imunologia , Fibras Nervosas Mielinizadas/ultraestrutura , Neurite Autoimune Experimental/imunologia , Fragmentos de Peptídeos/imunologia , Ratos Endogâmicos Lew
17.
Eur Radiol ; 29(11): 5910-5919, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30980123

RESUMO

OBJECTIVES: To quantitatively characterize diabetic amyotrophy (DA), or diabetic lumbosacral radiculoplexopathy, and compare with controls using magnetic resonance neurography (MRN). METHODS: Forty controls and 23 DA cases were analyzed qualitatively and quantitatively. Cross-sectional areas (CSAs) of bilateral L3 through S2 lumbosacral nerve roots, femoral nerves, and sciatic nerves (proximal and distal measurements) were measured. A linear model was used to assess the nerve location and case/control effect on angle-corrected CSAs. Intra- and inter-reader analysis was performed using intraclass correlation (ICC). RESULTS: In DA cases, abnormalities of the lumbosacral nerve roots, sciatic, femoral, and obturator nerves were seen in 21/23, 16/23, 21/23, and 9/23, respectively. Denervation abnormalities of multiple abdominopelvic muscles were seen. Quantitatively, the CSA of all measured LS plexus nerve roots and bilateral femoral nerves were significantly larger in DA cases vs. controls by 45% (95% CI, (30%, 49%); p < 0.001). The ICC was moderate for inter-rater analysis = 0.547 (95% CI, 0.456-0.626) and excellent for intra-rater analysis = 0.90 (95% CI, 0.89-92). CONCLUSIONS: Multifocal neuromuscular lesions related to diabetic amyotrophy were qualitatively and quantitatively detected on MRN. Qualitative abnormalities distinguished cases from controls, and nerve CSAs of cases were significantly larger than those of controls. Therefore, MRN may be employed as a non-invasive diagnostic tool for the evaluation of diabetic amyotrophy. KEY POINTS: • Qualitative abnormalities of lumbosacral nerve roots, their peripheral branches, and muscles are seen in DA. • The lumbosacral nerve roots and their peripheral branches in diabetic amyotrophy cases are significantly larger in cross-sectional area than non-diabetic subjects by 45% (95 CI, 30%, 49%; p < 0.001). • The ICC was moderate for inter-rater analysis = 0.547 (95% CI, 0.456-0.626) and excellent for intra-rater analysis = 0.90 (95% CI, 0.89-92).


Assuntos
Neuropatias Diabéticas/diagnóstico , Nervo Femoral/patologia , Plexo Lombossacral/patologia , Imagem por Ressonância Magnética/métodos , Nervo Isquiático/patologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
18.
Biomed Res Int ; 2019: 4252349, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30984781

RESUMO

Background: Local anesthetics are used in various purposes from topical and infiltration anesthesia to peripheral nerve or central neural blockade. Even though local anesthetics are relatively safe, they can have some toxic and adverse effects. Prolonged sensory and motor block is another example of an unwanted complication. The primary objective of this study was to determine whether insulin has a reversal effect on the peripheral (sciatic) nerve block with lidocaine or bupivacaine. Methods: The surgically exposed sciatic nerves in rats were blocked with lidocaine or bupivacaine, and then 0.1 ml of normal saline or 0.1 ml normal saline containing 0.1 IU a short-acting form of insulin was administrated per body in each group. Before and after sciatic nerve block, as well as until recovery from the nerve block after normal saline or insulin treatment, nerve conduction studies such as monitoring loss and recovery of the waveforms and amplitudes were performed to evaluate the status of motor nerve conduction. Results: Complete recovery time of nerve conduction status in lidocaine + normal saline group was 58 ± 16 min, whereas that in lidocaine + insulin group was 17 ± 3 min and the difference was statistically significant (p < 0.01). Complete recovery time of nerve conduction status in bupivacaine + normal saline group was 116 ± 16 min and that in bupivacaine + insulin group was 36 ± 4 min and the two groups were significantly different (p < 0.01). Conclusions: Insulin can reverse peripheral nerve block induced by lidocaine or bupivacaine.


Assuntos
Insulina/administração & dosagem , Bloqueio Nervoso/métodos , Nervo Isquiático/efeitos dos fármacos , Neuropatia Ciática/tratamento farmacológico , Anestesia Local/métodos , Animais , Bupivacaína/administração & dosagem , Modelos Animais de Doenças , Combinação de Medicamentos , Humanos , Lidocaína/administração & dosagem , Ratos , Nervo Isquiático/patologia , Neuropatia Ciática/patologia
19.
Biol Pharm Bull ; 42(4): 638-644, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30930422

RESUMO

Oxaliplatin has been used as a first choice for colorectal, gastric and pancreatic cancer, but it induces peripheral neuropathies. Dimethyl fumarate (DMF) is an oral drug for multiple sclerosis with neuroprotective effects on oxidative stress. Using both in vivo and in vitro models, we investigated the effects of DMF on oxaliplatin-induced peripheral neuropathy and other side effects, as well as on the anti-tumor activity of oxaliplatin. Repeated intraperitoneal injection of 4 mg/kg oxaliplatin (twice per week for 4 weeks) caused mechanical allodynia (as revealed by the von Frey tests), cold hyperalgesia (as revealed by the acetone tests), and axonal degeneration in the sciatic nerve of rats. Co-administration of oral DMF (200 mg/kg, five times per week for 4 weeks) relieved oxaliplatin-induced mechanical allodynia but not cold hyperalgesia, and ameliorated axonal degeneration. In addition, DMF did not exacerbate oxaliplatin-induced body weight loss or bone marrow suppression, such as reduction in red blood cells, white blood cells, neutrophils and lymphocytes. Furthermore, DMF did not inhibit the anti-tumor activity of oxaliplatin in any cultured cancer cell line (C26, mouse colon carcinoma; HCT116, human colon carcinoma; MKN45, human gastric adenocarcinoma; MIA PaCa-2, human pancreatic carcinoma) or C26-bearing mice. These results suggest that DMF prevents oxaliplatin-induced mechanical allodynia and axonal degeneration without affecting the anti-tumor activity of oxaliplatin. Therefore, DMF may be useful for managing oxaliplatin-induced chronic peripheral neuropathy.


Assuntos
Antineoplásicos , Fumarato de Dimetilo/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Oxaliplatina , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Fumarato de Dimetilo/farmacologia , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Masculino , Camundongos Endogâmicos BALB C , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fármacos Neuroprotetores/farmacologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Ratos Sprague-Dawley , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/patologia , Carga Tumoral/efeitos dos fármacos
20.
Anat Sci Int ; 94(4): 285-294, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30949912

RESUMO

Oxidative stress contributes to the progression of neurodegenerative diseases of the central and peripheral nervous systems, including Alzheimer's disease, Parkinson's disease, stroke, and diabetic neuropathy. Despite the greater capability of peripheral nerves to regenerate compared with those in the brain or spinal cord, chronic oxidative stress leads to irreversible neurodegeneration in peripheral nerves. Thus, many efforts have been made to defend against irreversible peripheral nerve degeneration and oxidative stress. Numerous phytochemicals have been revealed as antioxidants which neutralize free radicals and reduce peripheral neurocellular damage. Among them, polyphenols alleviate neurodegeneration by interacting with reactive oxygen species. Apigenin is a polyphenol found in plant-derived foods, including parsley, thyme, celery, and chamomile tea. Apigenin has been reported to exert antioxidative effects by scavenging free radicals. In particular, apigenin has a neuroprotective effect against oxidative stress in neurological disorders, such as cerebral ischemia. However, to date, no studies have shown an association of the inhibitory effect of apigenin with peripheral nerve degeneration. In this work, we showed that apigenin has a neuroprotective effect against peripheral nerve degeneration according to four key phenotypes: axonal degradation, myelin fragmentation, trans-dedifferentiation, and proliferation of Schwann cells via Krox20- and extracellular signal-regulated kinase-independent processes. Thus, apigenin could be a good candidate to treat peripheral neurodegenerative diseases.


Assuntos
Apigenina/farmacologia , Depuradores de Radicais Livres/farmacologia , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Animais , Apigenina/uso terapêutico , Axônios/efeitos dos fármacos , Axônios/patologia , Desdiferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Proteína 2 de Resposta de Crescimento Precoce/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Depuradores de Radicais Livres/uso terapêutico , Humanos , Masculino , Camundongos , Doenças Neurodegenerativas/patologia , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Doenças do Sistema Nervoso Periférico/patologia , Espécies Reativas de Oxigênio/metabolismo , Células de Schwann/efeitos dos fármacos , Células de Schwann/patologia , Nervo Isquiático/patologia
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