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1.
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
2.
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
3.
World Neurosurg ; 129: 170-171, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31181364

RESUMO

Intraneural hematomas are an uncommon cause of a focal mononeuropathy. When they do occur, it is usually in the setting of inherited or iatrogenic coagulopathies or as a consequence of injections targeting nerves. We report a man aged 68 years on warfarin therapy for a prior pulmonary embolism who presented with a 6-month history of progressive weakness of knee flexion and ankle movement, excruciating pain, and dense numbness in his posterior left thigh and below the knee, consistent with a severe high sciatic palsy. Imaging depicted a contiguous cystic mass of mixed T1 and T2 intensities involving the left sciatic nerve in the thigh, which was radiologically interpreted as a hip arthroplasty-associated pseudotumor. The patient underwent surgical exploration, which revealed a thick hemorrhagic pseudocompartment within the sciatic nerve. The histopathologic diagnosis was consistent with chronic hemorrhage. These impressive lesions should be included in the differential diagnosis of nerve masses.


Assuntos
Hematoma/patologia , Neuropatia Ciática/patologia , Idoso , Anticoagulantes/efeitos adversos , Hematoma/etiologia , Hematoma/cirurgia , Humanos , Masculino , Embolia Pulmonar/tratamento farmacológico , Neuropatia Ciática/etiologia , Neuropatia Ciática/cirurgia , Varfarina/efeitos adversos
4.
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
6.
Behav Pharmacol ; 30(1): 79-88, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30633724

RESUMO

Neuropathic pain is driven by abnormal peripheral and central processing, and treatments are insufficiently effective. Antibodies against nerve growth factor (anti-NGF) have been investigated as a potent analgesic treatment for numerous conditions. However, the peripheral and brain effects of anti-NGF in neuropathic pain remain unknown. We examined the effectiveness of anti-NGF in reducing chronic pain by local administration in a rat model of sciatic constriction injury (CCI). NGF and substance P in the dorsal root ganglion (DRG) and spinal cord were evaluated. Neuronal activation was measured using c-Fos in the anterior cingulate cortex and ventrolateral periaqueductal gray. At 14 days after CCI, anti-NGF promoted a significant dose-dependent improvement in mechanical threshold, thermal withdrawal latency, and cold sensitivity, lasting for 5 h. NGF upregulation in the DRG and spinal cord after CCI was decreased by anti-NGF, while substance P was increased only in the DRG, and the treatment reduced it. Anti-NGF induced a significant reduction of neuronal activation in the anterior cingulate cortex, but not in the ventrolateral periaqueductal gray. This study provides the first evidence of the anti-NGF effects on brain activity. Thus, our findings suggest that anti-NGF improves chronic neuropathic pain, acting directly on peripheral sensitization and indirectly on central sensitization.


Assuntos
Anticorpos/uso terapêutico , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Fator de Crescimento Neural/imunologia , Neuropatia Ciática/tratamento farmacológico , Neuropatia Ciática/patologia , Animais , Modelos Animais de Doenças , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Masculino , Medição da Dor , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Wistar , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Substância P/metabolismo , Fatores de Tempo , Regulação para Cima/efeitos dos fármacos
7.
Neuroscience ; 399: 125-134, 2019 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-30593918

RESUMO

MicroRNAs have been reported to be an important pathophysiological factor in neuropathic pain. However, the potential mechanism through which miRNAs function in neuropathic pain remains unclear. The purpose of this study was to explore the potential role of mir-34c in neuropathic pain in a mouse model of chronic constriction injury (CCI). We found that overexpression of miR-34c greatly alleviated CCI-induced neuropathic pain and spinal cord infarction, and reduced cell apoptotic and inflammatory cytokine expression in CCI mice. We also demonstrated that miR-34c suppressed the expression of NLRP3 by directly binding the 3'-untranslated region. Overexpression of miR-34c decreased the protein levels of NLRP3, ASC, caspase-1, IL-1ß, and IL-18 in the spinal cord in CCI mice. Together, our results indicated that miR-34c may inhibit neuropathic pain development in CCI mice through inhibiting NLRP3-mediated neuroinflammation.


Assuntos
Constrição Patológica/metabolismo , MicroRNAs/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Neuralgia/metabolismo , Neuropatia Ciática/metabolismo , Animais , Doença Crônica , Constrição Patológica/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica/fisiologia , Hiperalgesia/metabolismo , Hiperalgesia/patologia , Inflamassomos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Microglia/metabolismo , Microglia/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Neuralgia/etiologia , Neuralgia/patologia , Neurônios/metabolismo , Neurônios/patologia , Neuropatia Ciática/patologia , Medula Espinal/metabolismo , Medula Espinal/patologia , Temperatura Ambiente , Tato
8.
J Ultrasound Med ; 38(1): 157-164, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29732595

RESUMO

OBJECTIVES: The purpose of this study was to determine whether sciatic nerve stiffness is altered in people with chronic low back-related leg pain by using shear wave elastography. METHODS: In this cross-sectional study, the sciatic nerve shear wave velocity (ie, an index of stiffness) was measured in both legs of 16 participants (8 with unilateral low back-related leg pain and 8 healthy controls). Sciatic stiffness was measured during a passive ankle dorsiflexion motion performed at 2°/s in an isokinetic dynamometer. The ankle range of motion and passive torque, as well as muscle activity, were also measured. RESULTS: In people with low back-related leg pain, the affected limb showed higher sciatic nerve stiffness compared to the unaffected limb (+11.3%; P = .05). However, no differences were observed between the unaffected limb of people with low back-related leg pain and the healthy controls (P = .34). CONCLUSIONS: People with chronic low back-related leg pain have interlimb differences in sciatic nerve stiffness, as measured by a safe and noninvasive method: shear wave elastography. The changes found may be related to alterations in nerve mechanical properties, which should be confirmed by future investigations.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Dor Lombar/etiologia , Nervo Isquiático/diagnóstico por imagem , Nervo Isquiático/patologia , Neuropatia Ciática/diagnóstico por imagem , Neuropatia Ciática/patologia , Adolescente , Adulto , Dor Crônica/etiologia , Dor Crônica/fisiopatologia , Estudos Transversais , Eletromiografia , Feminino , Humanos , Perna (Membro)/fisiopatologia , Dor Lombar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
9.
Glia ; 67(2): 360-375, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30444070

RESUMO

Schwann cells (SCs), the primary glia in the peripheral nervous system (PNS), display remarkable plasticity in that fully mature SCs undergo dedifferentiation and convert to repair SCs upon nerve injury. Dedifferentiated SCs provide essential support for PNS regeneration by producing signals that enhance the survival and axon regrowth of damaged neurons, but the identities of neurotrophic factors remain incompletely understood. Here we show that SCs express and secrete progranulin (PGRN), depending on the differentiation status of SCs. PGRN expression and secretion markedly increased as primary SCs underwent dedifferentiation, while PGRN secretion was prevented by administration of cAMP, which induced SC differentiation. We also found that sciatic nerve injury, a physiological trigger of SC dedifferentiation, induced PGRN expression in SCs in vivo. These results suggest that dedifferentiated SCs express and secrete PGRN that functions as a paracrine factor to support the survival and axon growth of neighboring neurons after injury.


Assuntos
Axônios/patologia , Proliferação de Células/efeitos dos fármacos , Neurônios Motores/patologia , Progranulinas/metabolismo , Células de Schwann/metabolismo , Neuropatia Ciática/patologia , Animais , Axônios/efeitos dos fármacos , Bucladesina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Técnicas de Cocultura , Meios de Cultivo Condicionados/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Fluoresceínas/metabolismo , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos ICR , Neurônios Motores/efeitos dos fármacos , Progranulinas/farmacologia , RNA Mensageiro/metabolismo , Células de Schwann/química , Medula Espinal/citologia
10.
J Pharmacol Exp Ther ; 368(3): 490-502, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30591528

RESUMO

The combination of decellularized nerve allograft and adipose-derived stromal cells (ASCs) represents a good alternative to nerve autograft for bridging peripheral nerve defects by providing physical guidance and biologic cues. However, the regeneration outcome of acellular nerve allograft (ANA) is often inferior to autograft. Therefore, we hypothesized that acetyl-l-carnitine (ALCAR) treatment and implantation of ASC-embedded ANA would work synergistically to promote nerve regeneration. Seventy rats were randomly allocated into seven experimental groups (n = 10), including the healthy control group, sham surgery group, autograft group, ANA group, ANA + ASCs group, ANA + ALCAR group (50 mg/kg for 2 weeks), and ANA + ASCs + ALCAR (50 mg/kg for 2 weeks) group. All grafts were implanted to bridge long-gap (10-mm) sciatic nerve defects. Functional, electrophysiological, and morphologic analysis was conducted during the experimental period. We found that ALCAR potentiated the survival and retention of transplanted ASCs and upregulated the expression of neurotrophic factor mRNAs in transplanted grafts. Sixteen weeks following implantation in the rat, the ANA supplemented by ASCs was capable of supporting reinnervation across a 10-mm sciatic nerve gap, with results close to that of the autografts in terms of functional, electrophysiological, and histologic assessments. Results demonstrated that ALCAR treatment improved regenerative effects of ANA combined with ASCs on reconstruction of a 10-mm sciatic nerve defect in rat comparable to those of autograft.


Assuntos
Acetilcarnitina/administração & dosagem , Tecido Adiposo/transplante , Aloenxertos/transplante , Regeneração Nervosa/fisiologia , Neuropatia Ciática/terapia , Células Estromais/transplante , Derme Acelular/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/fisiologia , Aloenxertos/efeitos dos fármacos , Aloenxertos/fisiologia , Animais , Masculino , Regeneração Nervosa/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Wistar , Neuropatia Ciática/tratamento farmacológico , Neuropatia Ciática/patologia , Células Estromais/efeitos dos fármacos , Células Estromais/patologia , Complexo Vitamínico B/administração & dosagem
11.
J Med Case Rep ; 12(1): 391, 2018 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-30593288

RESUMO

BACKGROUND: Projectile foreign bodies are known to cause chronic heavy metal toxicity due to the release of metal into the bloodstream. However, the local effect around the metallic object has not been investigated and the main goal of our study is to examine the influence of the object in close proximity of the object. CASE PRESENTATION: A 36-year-old Caucasian woman with one metallic pellet close to her sciatic nerve due to a previous shotgun injury at the gluteal area presented with a diagnosis of recurrent lumbar disk herniation at L4-5 level. A physical examination confirmed chronic neuropathy and she underwent a two-stage surgery. The surgery included removal of the foreign body, followed by discectomy and fusion at the involved level. During the removal of the metallic foreign body, a tissue sample around the pellet and another tissue sample from a remote area were obtained. The samples were analyzed by scanning acoustic microscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. Lead, chromium, copper, cadmium, iron, manganese, selenium, and zinc elements in tissue, blood, and serum specimens were detected by inductively coupled plasma optical emission spectroscopy. CONCLUSIONS: An acoustic impedance map of the tissue closer to the metallic body showed higher values indicating further accumulation of elements. Energy-dispersive X-ray spectroscopy results confirmed scanning acoustic microscopy results by measuring a higher concentration of elements closer to the metallic body. Scanning electron microscopy images showed that original structure was not disturbed far away; however, deformation of the structure existed in the tissue closer to the foreign body. Element analysis showed that element levels within blood and serum were more or less within acceptable ranges; on the other hand, element levels within the tissues showed pronounced differences indicating primarily lead intoxication in the proximity of the metallic body. We can state that residues of metallic foreign bodies of gunshot injuries cause chronic metal infiltration to the surrounding tissue and induce significant damage to nearby neural elements; this is supported by the results of scanning acoustic microscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, and inductively coupled plasma optical emission spectroscopy.


Assuntos
Nádegas/diagnóstico por imagem , Corpos Estranhos/diagnóstico por imagem , Neuropatia Ciática/diagnóstico por imagem , Ferimentos por Arma de Fogo/diagnóstico por imagem , Adulto , Nádegas/patologia , Discotomia , Feminino , Corpos Estranhos/complicações , Humanos , Vértebras Lombares , Metais , Microscopia Acústica , Microscopia Eletrônica de Varredura , Neuropatia Ciática/etiologia , Neuropatia Ciática/patologia , Análise Espectral , Resultado do Tratamento , Ferimentos por Arma de Fogo/complicações
13.
Glia ; 66(12): 2632-2644, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30295958

RESUMO

Proper function of the nervous system depends on myelination. In peripheral nerves, Schwann cells (SCs) myelinate axons and the miRNA biogenesis pathway is required for developmental myelination and myelin maintenance. However, regulatory roles of this pathway at different stages of myelination are only partially understood. We addressed the requirement of the core miRNA biogenesis pathway components Dgcr8, Drosha, and Dicer in developing and adult SCs using mouse mutants with a comparative genetics and transcriptomics approach. We found that the microprocessor components Dgcr8 and Drosha are crucial for axonal radial sorting and to establish correct SC numbers upon myelination. Transcriptome analyses revealed a requirement of the microprocessor to prevent aberrantly increased expression of injury-response genes. Those genes are predicted targets of abundant miRNAs in sciatic nerves (SNs) during developmental myelination. In agreement, Dgcr8 and Dicer are required for proper maintenance of the myelinated SC state, where abundant miRNAs in adult SNs are predicted to target injury-response genes. We conclude that the miRNA biogenesis pathway in SCs is crucial for preventing inappropriate activity of injury-response genes in developing and adult SCs.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento/fisiologia , MicroRNAs/metabolismo , Células de Schwann/patologia , Neuropatia Ciática/patologia , Neuropatia Ciática/prevenção & controle , Transdução de Sinais/fisiologia , Animais , Animais Recém-Nascidos , Conexinas/genética , Conexinas/metabolismo , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , MicroRNAs/genética , Microscopia Eletrônica , Bainha de Mielina/patologia , Bainha de Mielina/ultraestrutura , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Ribonuclease III/genética , Ribonuclease III/metabolismo , Células de Schwann/metabolismo , Células de Schwann/ultraestrutura , Fatores de Transcrição/metabolismo
14.
Neurochem Res ; 43(12): 2423-2434, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30374602

RESUMO

Runx2, also known as Cbfa1, is a multifunctional transcription factor essential for osteoblast differentiation. It also plays major roles in chondrocyte maturation, mesenchymal stem cell differentiation, cleidocranial dysplasia, and the growth and metastasis of tumors. The present study was performed to investigate the functions of Runx2 in the differentiation and migration of Schwann cells and outgrowth of neurites after peripheral nervous system injury. In a model of sciatic nerve crush (SNC) injury, we found a gradual increase in the expression of Runx2, which reached a peak after 1 week. Immunofluorescence revealed increased expression of Runx2 in Schwann cells and axons after SNC injury. Runx2 and Oct-6 expression trends were consistent with each other in western blotting, and colocalization of Runx2 and Oct-6 was observed in immunofluorescence. In vitro, Runx2 promoted Schwann cell differentiation by activation of the Akt-GSK3ß signaling pathway. In addition, Runx2 promoted the migration of Schwann cells and outgrowth of neurites. These findings suggest that Runx2 may be involved in neurite outgrowth and Schwann cell differentiation and migration after sciatic nerve injury.


Assuntos
Diferenciação Celular/fisiologia , Movimento Celular/fisiologia , Subunidade alfa 1 de Fator de Ligação ao Core/biossíntese , Neuritos/metabolismo , Células de Schwann/metabolismo , Neuropatia Ciática/metabolismo , Animais , Masculino , Compressão Nervosa/tendências , Regeneração Nervosa/fisiologia , Neuritos/patologia , Ratos , Ratos Sprague-Dawley , Células de Schwann/patologia , Neuropatia Ciática/patologia
15.
Neurochem Res ; 43(12): 2404-2422, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30367337

RESUMO

Neuropathic pain is an intractable disease with few definitive therapeutic options. Anethole (AN) has been confirmed to possess potent anti-inflammatory and neuroprotective properties, but its effect on neuropathic pain has not been reported. The present study was designed to investigate the antinociceptive effect of AN on chronic constriction injury (CCI)-induced neuropathic pain in mice. AN (125, 250, and 500 mg/kg) and pregabalin (40 mg/kg) were intragastric administered for 8 consecutive days from the 7th day post-surgery. Behavioral parameters were measured on different days, namely, 0, 7, 8, 10, 12, and 14, from CCI operation. Additionally, electrophysiological and histopathological changes were analyzed on the 14th day. Afterward, immunofluorescence and Western blot were utilized to examine the activation of glial cells and the expression of inflammatory cytokines, respectively. AN treatment of CCI mice considerably alleviated hyperalgesia and allodynia, ameliorated abnormal sciatic nerve conduction, and restored injured sciatic nerves in a dose-dependent manner. Furthermore, AN suppressed the activation of glial cells, down-regulated pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin (IL-6, and IL-1ß), and up-regulated the anti-inflammatory cytokine (IL-10). These assays first indicated that AN exerted an antinociceptive effect on CCI-induced neuropathic pain, and might be attributed to the anti-inflammatory and neuroprotective activities of AN.


Assuntos
Anisóis/uso terapêutico , Neuralgia/patologia , Neuralgia/prevenção & controle , Fármacos Neuroprotetores/uso terapêutico , Neuropatia Ciática/tratamento farmacológico , Neuropatia Ciática/patologia , Animais , Constrição , Masculino , Camundongos , Camundongos Endogâmicos ICR , Neuralgia/etiologia , Neuropatia Ciática/complicações
16.
Einstein (Sao Paulo) ; 16(3): eAO4206, 2018 Sep 17.
Artigo em Inglês, Português | MEDLINE | ID: mdl-30231143

RESUMO

OBJECTIVE: To evaluate the effects of right sciatic nerve compression and cryotherapy on muscle tissue. METHODS: We used 42 male Wistar rats, subdivided in the following Groups Control, Injury 3, Injury 8 and Injury 15 submitted to nerve compression and euthanized in the 3rd, 8th and 15th day after surgery. The Cryotherapy Injury 3 was entailed treatment with cryotherapy by immersion of the animal in recipient for 20 minutes during 1 day, then animals were euthanized at the 3rd day after surgery, and the Cryotherapy Injury 8 and the Cryotherapy Injury 15 was treated for 6 days, and euthanized at the 8th and 15th day after surgery. Functional evaluation was performed by the grasping strength of the right pelvic limb. The right tibialis anterior muscles were evaluated for mass, smaller diameter and cross-sectional area. In the Cryotherapy Injury 8 and the Cryotherapy Injury 15 groups, the hydroxyproline was dosed in the right soles. RESULTS: In the compression there was a significant difference in the Injury Groups compared with the Control Group (p<0.05). In the smaller diameter, the compression in Control Group was higher than Injury 8 (p=0.0094), Injury 15 (p=0.002) and Cryotherapy Injury 15 (p<0.001) groups. The comparison between groups with euthanasia in the same post-operative period, a significant difference (p=0.0363) was seen in day 8th after surgery, and this result in Cryotherapy Injury Group was greater than Injury Group. In the fiber area, Control Group was also higher than the Injury 8 (p=0.0018), the Injury 15 (p<0.001) and the Cryotherapy Injury 15 (p<0.001). In hydroxyproline, no significant difference was seen between groups. CONCLUSION: Nerve damage resulted in decreased muscle strength and trophism, the cryotherapy delayed hypotrophy, but this effect did not persist after cessation of treatment.


Assuntos
Crioterapia/métodos , Síndromes de Compressão Nervosa/patologia , Síndromes de Compressão Nervosa/terapia , Nervo Isquiático/patologia , Neuropatia Ciática/patologia , Neuropatia Ciática/terapia , Animais , Modelos Animais de Doenças , Hipertrofia/fisiopatologia , Masculino , Debilidade Muscular/fisiopatologia , Síndromes de Compressão Nervosa/fisiopatologia , Distribuição Aleatória , Ratos Wistar , Valores de Referência , Reprodutibilidade dos Testes , Nervo Isquiático/fisiopatologia , Nervo Isquiático/cirurgia , Neuropatia Ciática/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
17.
Medicine (Baltimore) ; 97(36): e12254, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30200159

RESUMO

RATIONALE: Sciatic neuropathy has various causes; however, cases in which a pressure ulcer led to sciatic neuropathy have not been reported to date. PATIENT CONCERNS: A 33-year-old woman with no pre-existing mobility problems visited our department with the chief complaint of an extensive pressure ulcer and necrosis in her right buttock. She had a medical history of being bedridden for 2 days while in a coma due to a drug overdose 2 months previously. Physical examination revealed loss of sensation and foot drop in the right foot. DIAGNOSIS: Physical examination, magnetic resonance imaging, and nerve conduction studies were conducted; the patient was diagnosed with a common peroneal branch injury of the right sciatic nerve. INTERVENTIONS: The necrotic tissue was debrided and sciatic nerve decompression was performed, followed by frequent dressing changes. In addition, psychiatric treatment and physical therapy were performed simultaneously. OUTCOMES: The pressure ulcer decreased in size and healed to some extent with granulation tissue. However, gait disorders, accompanied by symptoms of sciatic neuropathy, continued. The patient was transferred to the department of gastroenterology for the treatment of toxic hepatitis, which occurred during her inpatient treatment. LESSONS: Physicians should be aware that sciatic neuropathy may occur during the treatment of patients with a pressure ulcer who exhibit no symptoms of paraplegia or quadriplegia. To prevent neuropathy, aggressive treatment of the pressure ulcer is necessary.


Assuntos
Lesão por Pressão/complicações , Neuropatia Ciática/etiologia , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Lesão por Pressão/diagnóstico por imagem , Lesão por Pressão/patologia , Lesão por Pressão/terapia , Neuropatia Ciática/diagnóstico por imagem , Neuropatia Ciática/patologia , Neuropatia Ciática/terapia
18.
Neurol Res ; 40(11): 955-962, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30091393

RESUMO

OBJECTIVE: This study aims to investigate morphological alterations caused by partial sciatic nerve ligation (PNL) and the efficacy of a moderate-intensity swimming training as therapeutic strategy for nerve regeneration. METHODS: A number of 30 male adult mice were equally divided in control, 14 days after PNL (PNL 14 days), 42 days after PNL (PNL 42 days), 70 days after PNL (PNL 70 days) and 5-week exercise training after 7 days post-lesion (PNL trained 35 days) groups. PNL trained 35 days group began with a 10-min session for 3 days and this time was gradually increased by 10 min every three sessions until the animals had swum for 50 min per session. Morphoquantitative analysis was carried out to assess nerve regeneration in each group. RESULTS: PNL 14 days group exhibited less degenerating signs than PNL 42 days group, where most post-lesion alterations were visualized. Nerve area and minimum diameter were significantly lower (p < 0.05) than control group. PNL 70 days group showed a greater degree of regenerating fibers and similar morphometric parameters to control group. PNL trained 35 days demonstrated signs of regeneration, reaching control group values in the morphometric analysis. DISCUSSION: PNL promotes great histopathological changes, which became more visible at 42 post-injury days. A natural nerve-regeneration tendency was observed throughout time, as observed in PNL 70 days group; nevertheless, moderate swimming training was found to be a therapeutic resource for nerve regeneration, accelerating such process from a morphoquantitative perspective. ABBREVIATIONS: ANOVA: One-way analysis of variance; BDNF: Brain-derived neurotrophic factor; FGF-2: Fibroblast growth factor 2; GDNF: Glial cell line derived neurotrophic factor; IGF: Insulin-link growth factor; IL-1ß: Interleukin-1ß; NGF: Neural growth factor; PBS: Phosphate-buffered saline; PNL: Partial sciatic nerve ligation.


Assuntos
Terapia por Exercício , Regeneração Nervosa , Neuropatia Ciática/patologia , Neuropatia Ciática/terapia , Natação , Animais , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos BALB C , Síndromes de Compressão Nervosa/patologia , Síndromes de Compressão Nervosa/terapia , Degeneração Neural/patologia , Degeneração Neural/terapia , Neuralgia/patologia , Neuralgia/terapia , Distribuição Aleatória , Nervo Isquiático/patologia
19.
Neurotox Res ; 34(3): 677-692, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30051419

RESUMO

The reversibility of chemotherapy-induced peripheral neuropathy (CIPN), a disabling and potentially permanent side effect of microtubule-targeting agents (MTAs), is becoming an increasingly important issue as treatment outcomes improve. The molecular mechanisms regulating the variability in time to onset, severity, and time to recovery from CIPN between the common MTAs paclitaxel and eribulin are unknown. Previously (Benbow et al. in Neurotox Res 29:299-313, 2016), we found that after 2 weeks of a maximum tolerated dose (MTD) in mice, paclitaxel treatment resulted in severe reductions in axon area density, higher frequency of myelin abnormalities, and increased numbers of Schwann cell nuclei in sciatic nerves. Biochemically, eribulin induced greater microtubule-stabilizing effects than paclitaxel. Here, we extended these comparative MTD studies to assess the recovery from these short-term effects of paclitaxel, eribulin, and a third MTA, ixabepilone, over the course of 6 months. Paclitaxel induced a persistent reduction in axon area density over the entire 6-month recovery period, unlike ixabepilone- or eribulin-treated animals. The abundance of myelin abnormalities rapidly declined after cessation of all drugs but recovered most slowly after paclitaxel treatment. Paclitaxel- and ixabepilone- but not eribulin-treated animals exhibited increased Schwann cell numbers during the recovery period. Tubulin composition and biochemistry rapidly returned from MTD-induced levels of α-tubulin, acetylated α-tubulin, and end-binding protein 1 to control levels following cessation of drug treatment. Taken together, sciatic nerve axons recovered more rapidly from morphological effects in eribulin- and ixabepilone-treated animals than in paclitaxel-treated animals and drug-induced increases in protein expression levels following paclitaxel and eribulin treatment were relatively transient.


Assuntos
Antineoplásicos/toxicidade , Neuropatia Ciática , Animais , Modelos Animais de Doenças , Epotilonas/toxicidade , Feminino , Furanos/toxicidade , Filamentos Intermediários/metabolismo , Cetonas/toxicidade , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Associadas aos Microtúbulos/metabolismo , Bainha de Mielina/efeitos dos fármacos , Bainha de Mielina/patologia , Paclitaxel/toxicidade , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia , Proteínas S100/metabolismo , Células de Schwann/efeitos dos fármacos , Células de Schwann/patologia , Neuropatia Ciática/induzido quimicamente , Neuropatia Ciática/metabolismo , Neuropatia Ciática/patologia , Fatores de Tempo , Tubulina (Proteína)/metabolismo
20.
Biomed Pharmacother ; 105: 907-914, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30021384

RESUMO

Type 1 diabetes (T1DM) affects approximately 1 in 500 children. Diabetic peripheral neuropathy (DPN) is the most common form of peripheral neuropathy in diabetes and is a significant risk factor for serious pathological change. It is difficult and costly to treat DPN and although there have been several pivotal trials. The development of new drugs to treat DPN remains a high priority. Trehalose is a naturally occurring disaccharide, which is indicated to prevent maternal type 1 diabetes-induced neural tube defects. Thus, the primary aim of this study is to determine whether trehalose ameliorates DPN-induced sciatic nerve injury in TIDM. To establish a T1DM mouse model, wild-type (WT) male C57BL/6 J mice were injected with streptozotocin (STZ). WT mice, T1DM mice, and mice fed with trehalose were assayed for myelin-related gene expression and with behavioral tests. To mimic high glucose in vivo, Schwann cells were cultured under high glucose conditions with or without trehalose. In addition, oxidative damage, apoptosis, and mitochondrial translocation of the pro-apoptotic B-cell lymphoma-2 (Bcl-2) family members were assessed in Schwann cells. Results showed that treatment by trehalose prevented DPN and preserved diabetes-decreased expression of myelin-related genes in T1DM mice. Furthermore, trehalose abolished diabetes-suppressed regeneration of the sciatic nerve. More importantly, trehalose suppressed high glucose-induced oxidative damage and apoptosis in Schwann cells. In summary, trehalose ameliorates DPN-induced sciatic nerve injury in T1DM by preventing apoptosis, which makes it a promising candidate for the treatment of DPN.


Assuntos
Apoptose/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Neuropatias Diabéticas/tratamento farmacológico , Células de Schwann/efeitos dos fármacos , Neuropatia Ciática/tratamento farmacológico , Trealose/uso terapêutico , Animais , Apoptose/fisiologia , Células Cultivadas , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/patologia , Neuropatias Diabéticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células de Schwann/patologia , Neuropatia Ciática/patologia , Estreptozocina/toxicidade , Trealose/farmacologia
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